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Sample records for rat kidney proteins

  1. Dietary protein effects on irradiated rat kidney function

    International Nuclear Information System (INIS)

    Mahler, P.A.; Yatuin, M.B.

    1984-01-01

    The authors have previously reported that unilaterally nephrectomized, kidney irradiated young male S-D rats have an increased median survival when placed on a low (4%) protein diet, as compared to a normal (20%) or high (50%) protein diet (200, 103, and 59 days respectively for 14 Gy irradiation). They have expanded these studies to examine the effects of irradiation and dietary protein levels on kidney function, by examining the parameters of blood urea nitrogen, serum creatinine, urine urea nitrogen, urine creatinine, urine osmolarity, urine volume, and water consumption. Irradiated 20% protein diet animals show an increase in water consumption and urine production and also a decrease in urine osmolarity, urine urea concentration and urine creatinine concentration. These changes all support the hypothesis the kidney irradiated rats fed a normal protein diet have a reduced capability to concentrate urine compared to nonirradiated control rats. Evaluation of the same parameters in irradiated rats fed a 4% protein diet does not indicate a similar loss of concentrating capability. Whether this protection is due to the growth inhibition of the 4% protein diet or some other phenomena remains to be determined

  2. Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

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    Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

    2015-05-01

    Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.

  3. Mitochondrial Respiration Is Decreased in Rat Kidney Following Fetal Exposure to a Maternal Low-Protein Diet

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    Sarah Engeham

    2012-01-01

    Full Text Available Maternal protein restriction in rat pregnancy is associated with impaired renal development and age-related loss of renal function in the resulting offspring. Pregnant rats were fed either control or low-protein (LP diets, and kidneys from their male offspring were collected at 4, 13, or 16 weeks of age. Mitochondrial state 3 and state 4 respiratory rates were decreased by a third in the LP exposed adults. The reduction in mitochondrial function was not explained by complex IV deficiency or altered expression of the complex I subunits that are typically associated with mitochondrial dysfunction. Similarly, there was no evidence that LP-exposure resulted in greater oxidative damage to the kidney, differential expression of ATP synthetase β-subunit, and ATP-ADP translocase 1. mRNA expression of uncoupling protein 2 was increased in adult rats exposed to LP in utero, but there was no evidence of differential expression at the protein level. Exposure to maternal undernutrition is associated with a decrease in mitochondrial respiration in kidneys of adult rats. In the absence of gross disturbances in respiratory chain protein expression, programming of coupling efficiency may explain the long-term impact of the maternal diet.

  4. Solubilization of rat kidney plasma membrane proteins associated with 3H-aldosterone

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    Ozegovic, B.; Dobrovic-Jenik, D.; Milkovic, S.

    1988-01-01

    The treatment of rat kidney plasma membranes with sodium dodecyl sulphate (SDS) did not essentially affect the ability of the membranes for 3 H-aldosterone binding as compared with the intact plasma membranes (Ozegovic et al., 1977). A gel filtration of 3 H-aldosterone - kidney plasma membranes complex on Sepharose 6B yielded 2 protein and 2 3 H-aldosterone peaks. The proteins which were eluted in the first peak were associated with the first 3 H-aldosterone peak while the second 3 H-aldosterone peak was eluted with Ve corresponding to Ve of free 3 H-aldosterone. Spironolactone, a competitive antagonist of aldosterone, prevented the binding of 3 H-aldosterone to the membrane proteins. The results demonstrated a high affinity of the kidney plasma membranes solubilized with SDS and a specificity of aldosterone binding to the plasma membrane proteins of higher molecular mass. (author)

  5. Matrix Gla Protein is Involved in Crystal Formation in Kidney of Hyperoxaluric Rats

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    Xiuli Lu

    2013-02-01

    Full Text Available Background: Matrix Gla protein (MGP is a molecular determinant regulating vascular calcification of the extracellular matrix. However, it is still unclear how MGP may be invovled in crystal formation in the kidney of hyperoxaluric rats. Methods: Male Sprague-Dawley rats were divided into the hyperoxaluric group and control group. Hyperoxaluric rats were administrated by 0.75% ethylene glycol (EG for up to 8 weeks. Renal MGP expression was detected by the standard avidin-biotin complex (ABC method. Renal crystal deposition was observed by a polarizing microscope. Total RNA and protein from the rat kidney tissue were extracted. The levels of MGP mRNA and protein expression were analyzed by the real-time polymerase chain reaction (RT-PCR and Western blot. Results: Hyperoxaluria was induced successfully in rats. The MGP was polarly distributed, on the apical membrane of renal tubular epithelial cells, and was found in the ascending thick limbs of Henle's loop (cTAL and the distal convoluted tubule (DCT in hyperoxaluric rats, its expression however, was present in the medullary collecting duct (MCD in stone-forming rats. Crystals with multilaminated structure formed in the injurious renal tubules with lack of MGP expression.MGP mRNA expression was significantly upregulated by the crystals' stimulations. Conclusion: Our results suggested that the MGP was involved in crystals formation by the continuous expression, distributing it polarly in the renal tubular cells and binding directly to the crystals.

  6. Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats.

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    Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Maślak, Edyta; Topolska, Kinga

    2015-03-01

    The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effects of immunosuppressive treatment on protein expression in rat kidney

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    Kędzierska K

    2014-09-01

    Full Text Available Karolina Kędzierska,1 Katarzyna Sporniak-Tutak,2 Krzysztof Sindrewicz,2 Joanna Bober,3 Leszek Domański,1 Mirosław Parafiniuk,4 Elżbieta Urasińska,5 Andrzej Ciechanowicz,6 Maciej Domański,1 Tomasz Smektała,2 Marek Masiuk,5 Wiesław Skrzypczak,6 Małgorzata Ożgo,6 Joanna Kabat-Koperska,1 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology, and Internal Medicine, 2Department of Dental Surgery, 3Department of Medical Chemistry, 4Department of Forensic Medicine, 5Department of Pathomorphology, Pomeranian Medical University, 6Department of Physiology, Cytobiology, and Proteomics, West Pomeranian University of Technology, Szczecin, Poland Abstract: The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents' toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins' synthesis. Very slight differences

  8. Binding of inorganic mercury by subcellular fractions and proteins of rat kidneys

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    Komsta-Szumska, E; Chmielnicka, J; Piotrowski, J K

    1976-01-01

    Inorganic mercury, administered to rats in a single dose of 0.5 mg Hg/kg is accumulated in the kidneys mainly in the soluble (54 percent) and nuclear (30 percent) fractions, showing decreasing tendency with time. Mitochondrial and microsomal fractions, initially accumulating approximately 11 and 6 percent of total Hg, show a tendency to increase the absolute level of Hg for the first week after administration. In the soluble fraction low-molecular weight, metallothioneinlike proteins are mainly responsible for the accumulation of mercury; in other fractions proteins of higher molecular weight prevail.

  9. The three-kidney rat

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    Provoost, A.P.; Van Aken, M.

    1984-01-01

    In contrast to the numerous research into the adaption of renal function when nephons are lost, much less attention has been paid to the effects of an extra kidney. Through the availability of inbred rat strains, techniques to transplant rat kidneys, and methods to measure total and individual kidney function repeatedly in the same animal, it became possible to study the renal function in rats with three kidneys. Adult male rats of a highly inbred Wistar strain were used. Nine recipients of a third kidney (3-K) were compared with 5 sham operated control (2-K) rats. The total GFR, as measured by the plasma clearance of Cr-5l EDTA, was taken 1,3,6,9, and 15 weeks after operation. The contribution of each kidney to the total renal function was determined by a Tc-99m DTPA scan performed at weeks 10 and 16. After transplantation the total GFR of 3-K rats was, in general, not different from the value before transplantation or from that of 2-K rats. The lack of increase of the GFR of 3-K rats was not the result of a non-functioning graft

  10. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

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    Indira Pokkunuri

    2016-01-01

    Full Text Available We examined the effects and mechanism of grape powder- (GP- mediated improvement, if any, on aging kidney function. Adult (3-month and aged (21-month Fischer 344 rats were treated without (controls and with GP (1.5% in drinking water and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1, which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions.

  11. TGP attenuates endoplasmic reticulum stress and regulates the expression of thioredoxin-interacting protein in the kidneys of diabetic rats.

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    Shao, Yunxia; Qi, Xiangming; Xu, Xinxing; Wang, Kun; Wu, Yonggui; Xia, Lingling

    2017-01-16

    Recent evidence suggests that the endoplasmic reticulum stress (ERS)-thioredoxin-interacting protein (TXNIP)-inflammation chain contributes to diabetic renal injury. The aim of the current study was to investigate whether total glucosides of peony (TGP) could inhibit ERS and attenuate up-regulation of TXNIP in the kidneys of rats with streptozotocin-induced diabetes. TGP was orally administered daily at a dose of 50, 100, or 200 mg/kg for 8 weeks. The expression of glucose-regulated protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (p-PERK), phosphor- eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), and TXNIP was assessed. Results indicated that TGP significantly decreased diabetes-induced albuminuria and it acted by down-regulating activation of the ERS-TXNIP-inflammation chain in the kidneys of diabetic rats. These findings indicate that renoprotection from TGP in diabetic rats possibly contributed to inhibition of ERS and decreased expression of TXNIP. These findings also offer a new perspective from which to study the molecular mechanisms of diabetic nephropathy and prevent its progression.

  12. Study of rat kidney transamidinase structure and regulation with monoclonal antibodies and the purification and characterization of human kidney transamidinase

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    Gross, M.D.

    1985-01-01

    The isolation of monoclonal antibodies to transamidinase made possible the development of an immunosorbent inhibition assay for transamidinase protein using a 125 I-labeled monoclonal antibody. This assay is a more direct measurement of transamidinase protein than the determination of the amount of polyclonal antibody required to precipitate the transamidinase activities. Rats were fed diets supplemented with creatine and/or glycine, and the amounts of transamidinase protein were determined with the assay using the monoclonal antibody. The transamidinase activities of kidneys from the rats fed the various supplemented diets ranged from 10 to 40% of the control values, whereas, the amounts of transamidinase protein were, in all instances no lower than 66% of the control values. Purified homogeneous rat kidney transamidinase and rat kidney supernatants were subjected to isoelectric focussing and four to five fractions of the enzyme were obtained. Polyclonal antibodies, but not the monoclonal antibodies were found by Western blotting experiments to recognize all the forms of the enzyme obtained by the isoelectric focussing. The author concluded that the monoclonal antibodies recognized forms of the enzyme that changed very little in amount, relative to the alterations in enzyme activities, when rats were fed a diet containing creatine

  13. Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

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    Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

    2012-08-01

    Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

  14. Study On The Effect Of Cooking Of Some Food Proteins By Short-Term Radiation (Microwave) On The Functions Of The Liver And Kidney In Albino Rats

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    Al-Marzooq, M.A.

    2014-01-01

    Five groups of albino male rats, every group consist of seven rats, were used to study the effect of microwave proteins on liver, kidney functions and blood parameters. Control group was fed on 10% casein. The 2nd one was fed on 10% protein from microwave chicken. The 3rd one was fed on 10% protein from boiled chicken. The 4th one was fed on 10% protein from microwave kidney beans. The 5th one was fed on 10% protein from boiled kidney beans. The time of experiment was seven weeks. The biochemical parameters included (cholesterol, LDL, HDL, total lipids, triglyceride, SGOT, SGPT, ALP, creatinin, uric acid and amino acids). The group of rats fed on microwave chicken showed more increase in cholesterol level than the group fed on boiled chicken. The group fed on microwave kidney beans showed decrease in cholesterol level. The group fed on microwave chicken showed decrease in HDL and increase in LDL. The highest activity of SGOT was shown in group fed on microwave kidney beans followed by the group fed on microwave chicken. The groups fed on boiled kidney beans and boiled chicken proteins showed significant increase in SGPT activity. The group fed on boiled kidney beans have the highest activity of ALP enzyme; but the group fed on microwave chicken showed increase in the activity of ALP enzyme compared to the control group. The feeding of microwave chicken leads to increase in creatinine and uric acid levels in comparison to the control group. Microwave cooking leads to little increase in all amino acids in comparison to the control group

  15. Effects of Melatonin and Epiphyseal Proteins on Fluoride-Induced Adverse Changes in Antioxidant Status of Heart, Liver, and Kidney of Rats

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    Vijay K. Bharti

    2014-01-01

    Full Text Available Several experimental and clinical reports indicated the oxidative stress-mediated adverse changes in vital organs of human and animal in fluoride (F toxicity. Therefore, the present study was undertaken to evaluate the therapeutic effect of buffalo (Bubalus bubalis epiphyseal (pineal proteins (BEP and melatonin (MEL against F-induced oxidative stress in heart, liver, and kidney of experimental adult female rats. To accomplish this experimental objective, twenty-four adult female Wistar rats (123–143 g body weights were divided into four groups, namely, control, F, F + BEP, and F + MEL and were administered sodium fluoride (NaF, 150 ppm elemental F in drinking water, MEL (10 mg/kg BW, i.p., and BEP (100 µg/kg BW, i.p. for 28 days. There were significantly P<0.05 high levels of lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase, glutathione reductase, and glutathione peroxidase in cardiac, hepatic, and renal tissues of F-treated rats. Administration of BEP and MEL in F-treated rats, however, significantly P<0.05 attenuated these adverse changes in all the target components of antioxidant defense system of cardiac, hepatic, and renal tissues. The present data suggest that F can induce oxidative stress in liver, heart, and kidney of female rats which may be a mechanism in F toxicity and these adverse effects can be ameliorated by buffalo (Bubalus bubalis epiphyseal proteins and melatonin by upregulation of antioxidant defense system of heart, liver, and kidney of rats.

  16. Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats.

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    Su, Jing; Zhang, Pei; Zhang, Jing-Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2010-03-01

    TGP, extracted from the traditional Chinese herb root of Paeonia lactiflora pall, has been shown to have therapeutic effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. In this study, the effects of TGP on oxidative stress were investigated in the kidney of diabetic rats induced by streptozotocin. TGP (50, 100, 200mg/kg) was orally administered once a day for 8 weeks. TGP treatment in all three doses significantly lowered 24 h urinary albumin excretion rate in diabetic rats and attenuated glomerular volume. TGP treatment with 100 and 200mg/kg significantly reduced indices for tubulointerstitial injury in diabetic rats. The level of MDA was significantly increased in the kidney of diabetic rats and attenuated by TGP treatment at the dose of 200mg/kg. TGP treatment in a dose-dependent manner decreased the level of 3-NT protein of the kidney which increased under diabetes. T-AOC was significantly reduced in diabetic rat kidney and remarkably increased by TGP treatment at the dose of 100 and 200mg/kg. Activity of antioxidant enzyme such as SOD, CAT was markedly elevated by TGP treatment with 200mg/kg. Western blot analysis showed that p-p38 MAPK and NF-kappaB p65 protein expression increased in diabetic rat kidney, which were significantly decreased by TGP treatment. It seems likely that oxidative stress is increased in the diabetic rat kidneys, while TGP can prevent diabetes-associated renal damage against oxidative stress.

  17. Purification of lysosomal phospholipase A and demonstration of proteins that inhibit phospholipase A in a lysosomal fraction from rat kidney cortex

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    Hostetler, K.Y.; Gardner, M.F.; Giordano, J.R.

    1986-01-01

    Phospholipase A has been isolated from a crude lysosomal fraction from rat kidney cortex and purified 7600-fold with a recovery of 9.8% of the starting activity. The purified enzyme is a glycoprotein having an isoelectric point of pH 5.4 and an apparent molecular weight of 30,000 by high-pressure liquid chromatography gel permeation. Naturally occurring inhibitors of lysosomal phospholipase A are present in two of the lysosomal-soluble protein fractions obtained in the purification. They inhibit hydrolysis of 1,2-di[1- 14 C]oleoylphosphatidylcholine by purified phospholipase A 1 with IC 50 values of 7-11 μg. The inhibition is abolished by preincubation with trypsin at 37 0 C, but preincubation with trypsin at 4 0 C has no effect, providing evidence that the inhibitors are proteins. The results suggest that the activity of lysosomal phospholipase A may be regulated in part by inhibitory proteins. Lysosomal phospholipase A from rat kidney hydrolyzes the sn-1 acyl group of phosphatidylcholine, does not require divalent cations for full activity, and is not inhibited by ethylenediaminetetraacetic acid. It has an acid pH optimum of 3.6-3.8. Neither rho-bromophenacyl bromide, diisopropyl fluorophosphate, nor mercuric ion inhibits phospholipase A 1 . In contrast to rat liver, which has two major isoenzymes of acid phospholipase A 1 , kidney cortex has only one isoenzyme of lysosomal phospholipase A 1

  18. Purification of lysosomal phospholipase A and demonstration of proteins that inhibit phospholipase A in a lysosomal fraction from rat kidney cortex

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    Hostetler, K.Y.; Gardner, M.F.; Giordano, J.R.

    1986-10-21

    Phospholipase A has been isolated from a crude lysosomal fraction from rat kidney cortex and purified 7600-fold with a recovery of 9.8% of the starting activity. The purified enzyme is a glycoprotein having an isoelectric point of pH 5.4 and an apparent molecular weight of 30,000 by high-pressure liquid chromatography gel permeation. Naturally occurring inhibitors of lysosomal phospholipase A are present in two of the lysosomal-soluble protein fractions obtained in the purification. They inhibit hydrolysis of 1,2-di(1-/sup 14/C)oleoylphosphatidylcholine by purified phospholipase A/sub 1/ with IC/sub 50/ values of 7-11 ..mu..g. The inhibition is abolished by preincubation with trypsin at 37/sup 0/C, but preincubation with trypsin at 4/sup 0/C has no effect, providing evidence that the inhibitors are proteins. The results suggest that the activity of lysosomal phospholipase A may be regulated in part by inhibitory proteins. Lysosomal phospholipase A from rat kidney hydrolyzes the sn-1 acyl group of phosphatidylcholine, does not require divalent cations for full activity, and is not inhibited by ethylenediaminetetraacetic acid. It has an acid pH optimum of 3.6-3.8. Neither rho-bromophenacyl bromide, diisopropyl fluorophosphate, nor mercuric ion inhibits phospholipase A/sub 1/. In contrast to rat liver, which has two major isoenzymes of acid phospholipase A/sub 1/, kidney cortex has only one isoenzyme of lysosomal phospholipase A/sub 1/.

  19. Kidney in potassium depletion. II. K+ handling by the isolated perfused rat kidney

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    Hayashi, M.; Katz, A.I.

    1987-01-01

    In a companion paper the authors reported a large increment in Na + -K + -ATPase activity and [ 3 H]ouabain binding the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na + -K + pumps in these animals may be involved in potassium reabsorption they examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FE/sub K/) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FE/sub K/ in kidneys from each K-depleted rat; similar results were obtained when kidneys were perfused with low and high potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na + -K + -ATPase observed in such animals

  20. Profiling of kidney vascular endothelial cell plasma membrane proteins by liquid chromatography-tandem mass spectrometry.

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    Liu, Zan; Xu, Bo; Nameta, Masaaki; Zhang, Ying; Magdeldin, Sameh; Yoshida, Yutaka; Yamamoto, Keiko; Fujinaka, Hidehiko; Yaoita, Eishin; Tasaki, Masayuki; Nakagawa, Yuki; Saito, Kazuhide; Takahashi, Kota; Yamamoto, Tadashi

    2013-06-01

    Vascular endothelial cells (VECs) play crucial roles in physiological and pathologic conditions in tissues and organs. Most of these roles are related to VEC plasma membrane proteins. In the kidney, VECs are closely associated with structures and functions; however, plasma membrane proteins in kidney VECs remain to be fully elucidated. Rat kidneys were perfused with cationic colloidal silica nanoparticles (CCSN) to label the VEC plasma membrane. The CCSN-labeled plasma membrane fraction was collected by gradient ultracentrifugation. The VEC plasma membrane or whole-kidney lysate proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and digested with trypsin in gels for liquid chromatography-tandem mass spectrometry. Enrichment analysis was then performed. The VEC plasma membrane proteins were purified by the CCSN method with high yield (approximately 20 μg from 1 g of rat kidney). By Mascot search, 582 proteins were identified in the VEC plasma membrane fraction, and 1,205 proteins were identified in the kidney lysate. In addition to 16 VEC marker proteins such as integrin beta-1 and intercellular adhesion molecule-2 (ICAM-2), 8 novel proteins such as Deltex 3-like protein and phosphatidylinositol binding clathrin assembly protein (PICALM) were identified. As expected, many key functions of plasma membranes in general and of endothelial cells in particular (i.e., leukocyte adhesion) were significantly overrepresented in the proteome of CCSN-labeled kidney VEC fraction. The CCSN method is a reliable technique for isolation of VEC plasma membrane from the kidney, and proteomic analysis followed by bioinformatics revealed the characteristics of in vivo VECs in the kidney.

  1. New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

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    Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu; Brittin,Sachi; Mohandas, Narla; Lecomte, Marie-Christine; Gascard, Philippe

    2005-06-17

    Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1 proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.

  2. Livolin Forte Ameliorates Cadmium-Induced Kidney Injury in Wistar Rats

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    Akomolafe Rufus O.

    2016-06-01

    Full Text Available The kidney, which is an integral part of the drug excretion system, was reported as one of the targets of cadmium toxicity. Early events of cadmium toxicity in the cell include a decrease in cell membrane fluidity, breakdown of its integrity, and impairment of its repair mechanisms. Phosphatidylcholine and vitamin E have a marked fluidizing effect on cellular membranes. We hypothesized that Livolin forte (LIV could attenuate kidney damage induced by cadmium in rats. Twenty-five adult male Wistar rats were divided into five groups of five rats each: group I (control group received 0.3 ml/kg/day of propylene glycol for six weeks; group II was given 5 mg/kg/day of cadmium (Cd i.p for 5 consecutive days; group III rats were treated in a similar way as group II but were allowed a recovery period of 4 weeks; group IV was treated with LIV (5.2 mg/kg/day for a period of 4 weeks after inducing renal injury with Cd similarly to group II; and group V was allowed a recovery period of 2 weeks after a 4-week LIV treatment (5.2 mg/kg/day following Cd administration. A significant increase in plasma creatinine, urea, uric acid, and TBARS were observed in groups II and III compared to the control rats. Significant reductions in total protein, glucose, and GSH activity were also recorded. The urine concentrations of creatinine, urea, and uric acid in groups II and III were significantly lower than the control group. Th is finding was accompanied by a significant decrease in creatinine and urea clearance. Post-treatment with LIV caused significant decreases in plasma creatinine, urea, uric acid, and TBARS. Significant increases in total protein, glucose, and GSH activity of groups IV and V were observed compared to group II. A significant increase in urine concentrations of creatinine, urea, and uric acid and significant decreases in total protein, glucose, and GSH activity were observed in groups IV and V compared to group II. Photomicrographs of the rat kidneys

  3. Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

    Science.gov (United States)

    Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

    2015-12-05

    This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

    International Nuclear Information System (INIS)

    Sonnenberg, J.; Pansini, A.R.; Christakos, S.

    1984-01-01

    A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney

  5. [Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic rat].

    Science.gov (United States)

    Chen, Weidong; Chang, Baochao; Zhang, Yan; Yang, Ping; Liu, Lei

    2015-05-01

    To observe the effect of rhein on the expression of SIRT1(Sirtuin 1) in kidney of diabetic rats, and to explore the role of rhein in protecting rat kidney against diabetic nephropathy and possible mechanism. The type 2 diabetic rats were induced by high-glucose and high-fat diet combined with streptozotocin (35 mg/kg body mass). Seventy-five eight-week-old male SD rats were randomly divided into 6 groups: normal group, diabetic group, low-, medium- and high-dose (50, 100, 150 mg/kg) rhein treatment groups and 10 mg/kg pioglitazone treatment group. The rats were given corresponding substances intragastrically once a day. At the end of the 16th week, the fasting plasma glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), serum creatinine (Scr) and 24 hours urine protein (24 h U-PRO) were determined. The renal hypertrophy index (KM/BM), insulin resistance index (HOMA-IR) were calculated. The pathological changes in renal tissues were examined by PAS staining under a light microscopy. The mean glomerular area (MGA) and mean glomerular volume (MGV) were measured by pathological image analysis system. Western blotting and real-time quantitative PCR were used to determine the expression of SIRT1 in renal tissues at protein and mRNA levels, respectively. The expression of SIRT1 was down-regulated in the kidney of diabetic rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and MGV significantly decreased and the histopathology of renal tissues were significantly improved in all treatment groups compared with diabetic group. The expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups and pioglitazone treatment group compared with diabetic group. The indicators in high-dose rhein treatment group were improved more significantly than those in the other groups. Correlation analysis showed that the expression of SIRT1 was negatively correlated with 24 h U-PRO and MGV. The expression of SIRT1 was

  6. Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

    Science.gov (United States)

    Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

    2017-07-29

    Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

    Science.gov (United States)

    Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

    2016-11-01

    Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

  8. Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Jin-jin LIU

    2013-09-01

    Full Text Available Objective To observe the effect of exenatide, a glucagon-like peptide-1 (GLP-1 receptor agonist, on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor (CTGF in the kidney of streptozotocin (STZ-induced type 1 diabetic rats, and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats. Methods Thirty male Sprague-Dawley (SD rats were divided into control group (group A, n=7 and diabetic model group (n=23. Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin. It was successful in 19 rats. Diabetic rats were randomly divided into diabetic control group (group B, n=10 and diabetic with treatment of exenatide group (group C, n=9. Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily. Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection. All rats were sacrificed after eight weeks. The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR. The protein expression of CTGF was detected by immunohistochemical staining. Results The levels of blood glucose, lipids, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the mRNA expressions of renal NOX4 and p22phox, and the protein expression of renal CTGF were significantly increased in group B compared with that in group A (P0.05. Conclusion Exenatide can decrease the expressions of renal NOX4, p22phox and CTGF, decline the index of urinary protein, and alleviate the kidney hypertrophy in type 1 diabetic rats, implying that exenatide exerted a protective effect on the kidney.

  9. Effect of total glucosides of paeony on the expression of nephrin in the kidneys from diabetic rats.

    Science.gov (United States)

    Zhang, Pei; Zhang, Jing-Jing; Su, Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2009-01-01

    Total glucosides of paeony (TGP), extracted from the traditional Chinese herb root of Paeonia lactiflora pall, have been shown to have a therapeutic role in experimental diabetic nephropathy including albuminuria. Recent investigation has identified nephrin, a podocyte-specific transmembrane protein, as a key regulator in the pathogenesis of diabetic albuminuria. The aim of this study was to investigate whether TGP can attenuate albuminuria through prevention of nephrin loss in the experimental diabetic nephropathy. Fifty male Munich-Wistar rats were obtained from the Experimental Animal Center of Anhui Medical University. These rats were divided into 5 groups (n = 10); normal group, control diabetic group, and 3 TGP treated diabetic groups at different concentrations. Diabetes was induced by streptozotocin, and TGP (50, 100, 200 mg/kg) was orally administered to the 3 TGP treated diabetic groups once a day for 8 weeks, respectively. Blood glucose and 24 hour urinary albumin excretion rate (AER) were measured. The expressions of nephrin, tumor necrosis factor-alpha (TNF-alpha), NF-kappaB p65 and 3-nitrotyrosine (3-NT) protein were determined by immunoinfluorescence or Western blot analysis in the kidneys. Elevated AER was markedly attenuated by TGP treatment in diabetic rats. There was a finely dotted linear epithelial staining of nephrin in normal group glomeruli. In contrast, the staining of glomeruli from untreated diabetic rats was attenuated, more diapersed, and clustered. This diabetic-induced loss of glomerular nephrin expression was prevented in a large degree in TGP-treated diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats, but significantly increased in the TGP treatment groups. The expressions of TNF-alpha, NF-kappaB p65 and 3-NT protein were significantly increased in the kidneys of diabetic rats, which were all significantly inhibited by TGP treatment. Our results showed that

  10. Smad signaling pathway in pathogenesis of kidney injury induced by calcium oxalate stone in rats

    Directory of Open Access Journals (Sweden)

    Fan Zhang

    2016-10-01

    Full Text Available Objective: To investigate the involvement of Smad signaling pathway in the pathogenesis of kidney injury induced by calcium oxalate stone in rats to provide a reference for clinical treatment. Methods: Clean SD rats were randomly divided into 3 group, namely the control group, model group and pirfenidone group. Ethylene glycol + αhydroxy vitamin D3 was used as a stone-inducing agent to replicate the renal calcium oxalate stone model. Rats in the pirfenidone group were treated with pirfenidone intragastric administration. The serum Cr, BUN and 24-hour oxalate and calcium in renal tissues were assayed. The expressions of Bax/ Bcl2 protein, Caspase3 protein, TGFβ, Smad1, Smad2 and Smad3 proteins were detected by the fluorescent quantitation PCR method. Results: Compared with the rats of the control group, the results showed that the levels of serum BUN, Cr and 24-hour oxalate in rats of the model group were increased greatly, Bax and Caspase3 mRNA also increased while the level of Bcl2 decreased significantly, and the expressions of TGFβ, Smad1, Smad2 and Smad3 proteins increased distinctly as well (P<0.01. These abnormal parameters could be normalized effectively by pirfenidone. Conclusions: Activated TGFβ/Smad signaling pathway is involved in the pathogenesis of kidney injury induced by calcium oxalate stone in rats.

  11. Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. (Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge (England))

    1991-07-01

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

  12. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    International Nuclear Information System (INIS)

    Al-Kafaji, Ghada; Malik, Afshan N.

    2010-01-01

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as μ-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 ± 50 vs 147 ± 54, p < 0.05), and hearts (1583 ± 277 vs 191 ± 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 ± 37 vs 18 ± 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  13. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Al-Kafaji, Ghada [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom); Malik, Afshan N., E-mail: afshan.malik@kcl.ac.uk [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom)

    2010-01-22

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  14. Lithium induces microcysts and polyuria in adolescent rat kidney independent of cyclooxygenase‐2

    Science.gov (United States)

    Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels; Jensen, Boye L.

    2014-01-01

    Abstract In patients, chronic treatment with lithium leads to renal microcysts and nephrogenic diabetes insipidus (NDI). It was hypothesized that renal cyclooxygenase‐2 (COX‐2) activity promotes microcyst formation and NDI. Kidney microcysts were induced in male adolescent rats by feeding dams with lithium (50 mmol/kg chow) from postnatal days 7–34. Lithium treatment induced somatic growth retardation, renal microcysts and dilatations in cortical collecting duct; it increased cortical cell proliferation and inactive pGSK‐3β abundance; it lowered aquaporin‐2 (AQP2) protein abundance and induced polyuria with decreased ability to concentrate the urine; and it increased COX‐2 protein level in thick ascending limb. Concomitant treatment with lithium and a specific COX‐2 inhibitor, parecoxib (5 mg/kg per day, P10–P34), did not prevent lithium‐induced microcysts and polyuria, but improved urine concentrating ability transiently after a 1‐desamino‐8‐D‐arginine vasopressin challenge. COX‐2 inhibition did not reduce cortical lithium‐induced cell proliferation and phosphorylation of glycogen synthase kinase‐3β (GSK‐3β). COX‐1 protein abundance increased in rat kidney cortex in response to lithium. COX‐1 immunoreactivity was found in microcyst epithelium in rat kidney. A human nephrectomy specimen from a patient treated for 28 years with lithium displayed multiple, COX‐1‐immunopositive, microcysts. In chronic lithium‐treated adolescent rats, COX‐2 is not colocalized with microcystic epithelium, mitotic activity, and inactive pGSK‐3β in collecting duct; a blocker of COX‐2 does not prevent cell proliferation, cyst formation, or GSK‐3β inactivation. It is concluded that COX‐2 activity is not the primary cause for microcysts and polyuria in a NaCl‐substituted rat model of lithium nephropathy. COX‐1 is a relevant candidate to affect the injured epithelium. PMID:24744881

  15. [Effect of total glucosides of paeony on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats].

    Science.gov (United States)

    Chang, Bao-Chao; Chen, Wei-Dong; Zhang, Yan; Yang, Ping; Liu, Lei; Wang, Jing

    2014-10-01

    The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic

  16. Effects of mercury on lysosomal protein digestion in the kidney proximal tubule

    International Nuclear Information System (INIS)

    Madsen, K.M.; Christensen, E.I.

    1978-01-01

    The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125 I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication

  17. Localisation of selected Ca2+-transport systems in rat's heart and kidney and their modulation by stress

    International Nuclear Information System (INIS)

    Zacikova, L.

    2000-01-01

    This thesis deals with the identification of selected calcium transport systems and their modulation by immobilization stress in rat heart and kidney. In our experiments we used normotensive (Sprague-Dawley, Wistar-Kyoto) and hypertensive (SHR) strains. We compared mRNA levels, protein expression and activity of the Na + /Ca 2+ exchanger from hearts of control animals, animals subjected to a single (once) or repeated (seven times) immobilization stress and from animals treated continually with cortisol. We have observed that immobilization stress increased both, gene expression and protein message of the Na + /Ca 2 + exchanger in rat cardiac left, but not right ventricle. This effect is not mediated through the glucocorticoid responsive element. We have found that cortisol decreased activity of the N a +/Ca 2+ exchanger without changing expression and protein amount of this transport system. IP3 receptor of type I and 2 was detected on mRNA levels in rat cardiac atria. Very small amounts of these receptors were observed in rat cardiac ventricles. Since it was difficult to detect these amounts in ventricles, we used 'seminested' PCR to verify expression of IP 3 R1 and 2 in cardiac ventricles. The highest levels of IP 3 R1 and 2 were expressed in left atria. Immobilization stress significantly increased mRNA IP 3 R1 and 2 in rat cardiac atria. We observed both, mRNA and type 1 IP 3 receptor's protein in renal medulla, but not in renal cortex. We have found that this receptor was approximately twice as abundant in normotensive as in genetically hypertensive rat kidney. Immobilization stress significantly down-regulated IP 3 R1 in renal medulla, but not in renal cortex. To investigate the role of NAADP in signaling we measured 45 Ca 2+ release from rat cardiac microsomes. We examined concentration and time dependence of 45 Ca 2+ release from rat cardiac microsomes. All these results could contribute to the understanding of Ca 2+ modulation in cardiac and kidney under

  18. Effects of dietary protein quality and quantity on albino rat tissue ...

    African Journals Online (AJOL)

    Effects of dietary protein quality and quantity on albino rat tissue serum protein, erythrocyte fragility and bone mineral content. ... The 20% protein diet was a commercial diet better in nutrient composition and quality than the diet containing 17 and 15% protein formulated in our laboratory. At the end of 21 days, kidney, testes, ...

  19. Hypertension after bilateral kidney irradiation in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

  20. Influence of protein deficiency on cadmium toxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tewari, P C; Jain, V K; Ashquin, M; Tandon, S K

    1986-07-01

    The effects of a low protein diet on the body uptake and retention of cadmium, levels of essential trace elements, and cadmium-induced biochemical alterations in liver and kidneys of the rat were investigated. Low dietary protein disturbs cadmium induced alterations in carbohydrate metabolism, essential trace elements metabolism and offsets the hepatic and renal process of cadmium detoxification. Protein malnutrition enhances the susceptibility to cadmium intoxication.

  1. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

    Directory of Open Access Journals (Sweden)

    McCooke John K

    2012-08-01

    Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

  2. Effect of dental materials on gluconeogenesis in rat kidney tubules

    NARCIS (Netherlands)

    Reichl, F.X.; Durner, J.; Mückter, H.; Elsenhans, B.; Forth, W.; Kunzelmann, K.H.; Hickel, R.; Spahl, W.; Hume, W.R.; Moes, G.W.

    1999-01-01

    The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl2) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were

  3. Morphological characteristics of renal artery and kidney in rats.

    Science.gov (United States)

    Yoldas, Atilla; Dayan, Mustafa Orhun

    2014-01-01

    The gross anatomy and morphometry of the kidney and renal arteries were studied in the strains of laboratory rat: Sprague-Dawley (Sp) and Wistar (W) rats. Total of 106 three-dimensional endocasts of the intrarenal arteries of kidney that were prepared using standard injection-corrosion techniques were examined. A single renal artery was observed in 100% of the cases. The renal arteries were divided into a dorsal and a ventral branch. The dorsal and ventral branches were divided into two branches, the cranial and caudal branch. Renal arteries were classified into types I and II, depending on the cranial and caudal branches and their made of branching. The present study also showed that the right kidney was slightly heavier than the left one and that the kidney of the male was generally larger than that of the female. The mean live weights of the Sprague-Dawley and Wistar rats were found to be 258.26 ± 5.9 and 182.4 ± 19.05 g, respectively. The kidney weights were significantly correlated (P kidney weights were not found significantly correlated (P > 0.01) with the length of renal arteries.

  4. Neptunium 237 behaviour in subcellular fractions of rat kidneys

    International Nuclear Information System (INIS)

    Kreslov, V.V.; Maksutova, A.Ya.; Mushkacheva, G.S.

    1978-01-01

    Subcellular distribution of intravenously injected (1 and 0.5 μCi/rat) neptunium nitrate (5- and 6-valent) in kidneys of rat males and females has been investigated. It has been shown that the radionuclide was unevenly distributed within the cell. As early as 24 hours after administration, about 50 per cent of neptunium were concentrated in the mitochondrial fraction. The data are presented on variations in neptunium behaviour within subcellular fractions of rat kidneys depending on the sex of animals, valency and dose of the isotope

  5. Short-term treatment with diminazene aceturate ameliorates the reduction in kidney ACE2 activity in rats with subtotal nephrectomy.

    Directory of Open Access Journals (Sweden)

    Elena Velkoska

    Full Text Available Angiotensin converting enzyme (ACE 2 is an important modulator of the renin angiotensin system (RAS through its role to degrade angiotensin (Ang II. Depletion of kidney ACE2 occurs following kidney injury due to renal mass reduction and may contribute to progressive kidney disease. This study assessed the effect of diminazine aceturate (DIZE, which has been described as an ACE2 activator, on kidney ACE2 mRNA and activity in rats with kidney injury due to subtotal nephrectomy (STNx. Sprague Dawley rats were divided into Control groups or underwent STNx; rats then received vehicle or the DIZE (s.c. 15 mg/kg/day for 2 weeks. STNx led to hypertension (P<0.01, kidney hypertrophy (P<0.001 and impaired kidney function (P<0.001 compared to Control rats. STNx was associated with increased kidney cortical ACE activity, and reduced ACE2 mRNA in the cortex (P<0.01, with reduced cortical and medullary ACE2 activity (P<0.05, and increased urinary ACE2 excretion (P<0.05 compared to Control rats. Urinary ACE2 activity correlated positively with urinary protein excretion (P<0.001, and negatively with creatinine clearance (P=0.04. In STNx rats, DIZE had no effect on blood pressure or kidney function, but was associated with reduced cortical ACE activity (P<0.01, increased cortical ACE2 mRNA (P<0.05 and increased cortical and medullary ACE2 activity (P<0.05. The precise in vivo mechanism of action of DIZE is not clear, and its effects to increase ACE2 activity may be secondary to an increase in ACE2 mRNA abundance. In ex vivo studies, DIZE did not increase ACE2 activity in either Control or STNx kidney cortical membranes. It is not yet known if chronic administration of DIZE has long-term benefits to slow the progression of kidney disease.

  6. CA V is present in rat kidney mitochondria

    International Nuclear Information System (INIS)

    Dodgson, S.J.; Contino, L.C.

    1987-01-01

    Guinea pig liver mitochondria contain the unique carbonic anhydrase isozyme, CA V. Prior to sacrifice, 15 rats and 15 guinea pigs were either fed normal lab chow (group 1), starved 48 hours (group 2) or fed normal lab chow and given to drink only water with added HCl, pH 2.5 (group 3). Mitochondria were prepared from excised livers and kidneys. CA V activity of disrupted mitochondria was measured by 18 O-mass spectrometric technique at pH 7.4, 37 0 C, 25 mM NaHCO 3 . Mass spectrometric CA assays with intact kidney mitochondria localize CA V activity to the matrix, as was found for liver mitochondria. It has been shown in hepatocytes prepared from starved guinea pigs and rats that inhibition of CA V results in decreased rate of gluconeogenesis from pyruvate. These present results are in line with the published observation that rat kidneys are much more gluconeogenic than guinea pig, and that this is increased by starvation and acidosis

  7. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

    Science.gov (United States)

    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

  8. Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Xiao Wei

    2018-01-01

    Full Text Available Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA, and matrix Gla protein (MGP in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r=0.929; P<0.01 and serum BMP-4 (r=0.702; P<0.01 levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

  9. Study of histopathological and molecular changes of rat kidney under simulated weightlessness and resistance training protective effect.

    Directory of Open Access Journals (Sweden)

    Ye Ding

    Full Text Available To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78, one of the endoplasmic reticulum (ER chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration.

  10. Study of Histopathological and Molecular Changes of Rat Kidney under Simulated Weightlessness and Resistance Training Protective Effect

    Science.gov (United States)

    Li, Zhili; Tian, Jijing; Abdelalim, Saed; Du, Fang; She, Ruiping; Wang, Desheng; Tan, Cheng; Wang, Huijuan; Chen, Wenjuan; Lv, Dongqiang; Chang, Lingling

    2011-01-01

    To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration. PMID:21625440

  11. Degradation of Kidney and Psoas Muscle Proteins as Indicators of Post-Mortem Interval in a Rat Model, with Use of Lateral Flow Technology.

    Directory of Open Access Journals (Sweden)

    Dong-Gi Lee

    Full Text Available We investigated potential protein markers of post-mortem interval (PMI using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS and glycogen synthase kinase-3β were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase α, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and β-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA. The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene.

  12. Kidney gene expression analysis in a rat model of intrauterine growth restriction reveals massive alterations of coagulation genes.

    Science.gov (United States)

    Buffat, Christophe; Boubred, Farid; Mondon, Françoise; Chelbi, Sonia T; Feuerstein, Jean-Marc; Lelièvre-Pégorier, Martine; Vaiman, Daniel; Simeoni, Umberto

    2007-11-01

    In this study, low birth weight was induced in rats by feeding the dams with a low-protein diet during pregnancy. Kidneys from the fetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated with a reduction in nephrons number. To better understand the molecular basis of this observation, a transcriptome analysis contrasting kidneys from control and protein-deprived rats was performed, using a platform based upon long isothermic oligonucleotides, strengthening the robustness of the results. We could identify over 1800 transcripts modified more than twice (772 induced and 1040 repressed). Genes of either category were automatically classified according to functional criteria, making it possible to bring to light a large cluster of genes involved in coagulation and complement cascades. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites, suggesting an overrepresentation of the AP1R binding site, together with the transcription induction of factors actually binding to this site in the set of induced genes. The induction of coagulation cascades in the kidney of low-birth-weight rats provides a putative rationale for explaining thrombo-endothelial disorders also observed in intrauterine growth-restricted human newborns. These alterations in the kidneys have been reported as a probable cause for cardiovascular diseases in the adult.

  13. Structural transition of kidney cystatin in dimethylnitrosamine-induced renal cancer in rats: identification as a novel biomarker for kidney cancer and prognosis.

    Science.gov (United States)

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

    2017-04-01

    In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.

  14. The membrane fraction of homogenized rat kidney contains an enzyme that releases epidermal growth factor from the kidney membranes

    DEFF Research Database (Denmark)

    Nexø, Ebba; Poulsen, Steen Seier

    1991-01-01

    shows that the membrane fraction of homogenized rat kidney contains an enzyme that releases immuno and receptor reactive EGF from the kidney membranes when incubated at 37 degrees C. Gel filtration shows that the EGF reactivity released from the membranes is similar to the EGF reactivity in rat urine......High levels of epidermal growth factor (EGF) are excreted in the urine and high levels of mRNA for the EGF-precursor have been demonstrated in the kidney. The EGF-precursor is a membrane bound peptide in the kidney, but little is known about the renal processing of the precursor. The present study...

  15. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    International Nuclear Information System (INIS)

    Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

    2006-01-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

  16. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

    2006-12-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

  17. Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC-α, β and γ in the kidney of orchidectomized adult male Sprague–Dawley rats

    Directory of Open Access Journals (Sweden)

    Su Yi Loh

    2016-06-01

    Full Text Available Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of α, β and γ-epithelial sodium channel (ENaC proteins and messenger RNAs (mRNAs in kidneys, the channel known to be involved in Na+ reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague–Dawley (SD rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 µg/kg/day or 250 µg/kg/day with or without flutamide (androgen receptor blocker or finasteride (5α-reductase inhibitor. Following sacrifice, the kidneys were removed and were subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR respectively. The distribution of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Results. The α, β and γ-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, α, β and γ-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of α, β and γ-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in α, β and γ-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na+ reabsorption which subsequently might cause an increase in blood pressure.

  18. Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage.

    Science.gov (United States)

    Oyagbemi, Ademola A; Odetola, Adebimpe A

    2013-10-01

    This study was designed to evaluate the ameliorative and hypocholesterolemic effects of dietary supplementation of Cnidoscolus aconitifolius leaf meal (CALM) on hepatic injury and kidney injury associated with protein energy malnutrition (PEM). In this study, PEM was induced in weaning male Wistar albino rats by feeding them with low protein diet for 2 weeks. The effects of several recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed were assessed in PEM rats. Plasma biochemical parameters were assessed as well. After the induction of PEM, results obtained showed significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (T.P), total bilirubin (T.Bil), triglycerides, total cholesterol, low density lipoproteins (LDL), blood urea nitrogen (BUN), and creatinine with significant reduction in plasma high density lipoproteins (HDL), albumin, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)), bicarbonate (HC03(-)), and phosphate (P04(2-)) in PEM rats. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks caused significant (P protein deficient diets has a protective role against hepatic injury and renal damage associated with PEM.

  19. Curative effect of sesame oil in a rat model of chronic kidney disease.

    Science.gov (United States)

    Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

    2015-12-01

    Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

  20. Gene expression and enzyme activities of carbonic anhydrase and glutaminase in rat kidneys induced by chronic systemic hypoxia

    Directory of Open Access Journals (Sweden)

    Andi N.K. Syarifin

    2015-11-01

    Full Text Available Background: Hypoxia can cause acidosis. Kidney plays an essential role in maintaining acid-base balance, which involves the activities of carbonic anhydrase (CA and glutaminase (GLS. This study is aimed to determine the expression and activities of the CA9 and GLS1 enzymes in relation to hypoxia inducible factor-1α (HIF-1α, a transcription factor protein which is a marker of hypoxia.Methods: This study was an in vivo experimental study with coupled paralel design. used 25 male Sprague-Dawley rats weighing 150-200 g. Rats were divided into 5 groups: the control group (normoxic condition and 4 treatment groups. The latter were kept in a hypoxic chamber (10% O2: 90% N2 for 1, 3, 5 and 7 days. All rats were euthanized after treatment, kidneys excised, tissues homogenized and investigated for gene expression of CA9, GLS1 and HIF-1α. On protein level, total enzymatic activities of CA and GLS and protein of HIF-1α were also investigated. Data were analyzed statistically using ANOVA for significance, and as its alternative, used Mann-Whitney and Kruskal-Wallis test.Results: Results showed that HIF-1α mRNA increased during hypoxia, but not HIF-1α protein. It seemed that acidosis occurs in kidney tissue, indicated by increased CA9 and GLS1 mRNA expression and specific activity of total CA and GLS1. Expression of CA9 and GLS1 mRNA both showed strong positive correlation with HIF-1α mRNA, but not with HIF-1α protein.Conclusion: It is suggested that during chronic systemic hypoxia, gene expression of CA9 and GLS1 and their enzyme activities were increased as a response to acidosis and related with the expression of HIF-1α mRNA.

  1. Optical cryoimaging for assessment of radiation-induced injury to rat kidney metabolic state

    Science.gov (United States)

    Mehrvar, Shima; Funding la Cour, Mette; Medhora, Meetha; Camara, Amadou K. S.; Ranji, Mahsa

    2018-02-01

    Objective: This study utilizes fluorescence cryoimaging to quantitatively assess the effect of a high dose of irradiation on rat renal metabolism through redox state. Introduction: Exposure to high doses of irradiation could lead to death, in part, due to renal dysfunction. The kidney is one of the most sensitive organs that exhibit delayed injuries in survivors of acute radiation syndrome. In this study, optical cryoimaging was utilized to examine the potential for renal mitochondrial dysfunction after partial-body irradiation (PBI) and the mitigating effect of lisinopril-treatment, an angiotensin converting enzyme inhibitor that is FDA-approved for other indications. Materials and methods: Rats were exposed to a single dose of 13 Gy leg-out partial body irradiation (PBI, by X-rays). Rats (n = 5/group) received no further treatment, or lisinopril started one week after irradiation and continued at 24 mg/m2 /day. The non-irradiated siblings were used as controls. After 150 days, the rats were sacrificed, and their kidneys harvested and snap frozen in liquid nitrogen for later cryoimaging. The 3D images of metabolic indices (NADH and FAD) were captured, and the redox ratio i.e. NADH/FAD was calculated. The mitochondrial redox state of three groups of rat kidneys were quantified by calculating the volumetric mean of redox ratio images (RR). Results: 3D cryoimaging revealed that in PBI only kidneys, the metabolic marker (RR) decreased significantly by 78% compared to non-irradiated controls. Treatment with lisinopril significantly improved the RR by 93% in groups exposed to PBI. Conclusion: This study aimed at quantifying the level of the mitochondrial redox state of irradiated rat kidneys compared to non-irradiated kidneys (controls) and the efficacy of lisinopril to preserve kidney metabolism after irradiation. PBI oxidized the metabolic state of kidneys and lisinopril mitigated the radiation-induced injury on renal mitochondria.

  2. Characterization with 3H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

    International Nuclear Information System (INIS)

    Nakajima, Tohru; Kuruma, Isami

    1980-01-01

    The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of 3 H-haloperidol binding. Binding of 3 H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the 3 H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum. (author)

  3. Activity of cAMP-dependent protein kinases and cAMP-binding proteins of rat kidney cytosol during dehydration

    International Nuclear Information System (INIS)

    Zelenina, M.N.; Solenov, E.I.; Ivanova, L.N.

    1985-01-01

    The activity of cAMP-dependent protein kinases, the binding of cAMP, and the spectrum of cAMP-binding proteins in the cytosol of the renal papilla was studied in intact rats and in rats after 24 h on a water-deprived diet. It was found that the activation of protein kinases by 10 -6 M cAMP is significantly higher in the experimental animals than in the intact animals. In chromatography on DEAE-cellulose, the positions of the peaks of specific reception of cAMP corresponded to the peaks of the regulatory subunits of cAMP-dependent protein kinases of types I and II. In this case, in intact animals more than 80% of the binding activity was detected in peaks II, whereas in rats subjected to water deprivation, more than 60% of the binding was observed in peak I. The general regulatory activity of the cytosol was unchanged in the experimental animals in comparison with intact animals. It is suggested that during dehydration there is an induction of the synthesis of the regulatory subunit of type I cAMP-dependent protein kinase in the renal papilla

  4. Volume effect on the radiation injury of rat kidney

    International Nuclear Information System (INIS)

    Lo, Y.-C.; Kutcher, Gerald J.; Ling, Clifton C.

    1996-01-01

    Purpose: To minimize the likelihood of radiation-induced kidney injury in treating tumors, the relationship of tolerance dose and irradiated volume of kidney should be known. We have used a rat model to determine the dose-response relationship when various volumes of the kidney are irradiated. Methods and Materials: Anesthetized adult male rats (CD, 10-12 week old) were irradiated with 250 KV x-rays. The kidney was exteriorized and placed in a jig designed to shield all other tissues. Graded single doses were delivered to each of four volumes: 1/4V (half of one kidney), 1/2V (one whole kidney, or half of each kidney), 3/4V (one and a half kidneys) and 1V, where V is the volume of both kidneys. In addition, to compare radiation injury and surgery, partial nephrectomy was performed for 1/4V, 1/2V and 3/4V. Four to sixteen rats were used for each dose-volume point. The rats have been followed up for 540 days. The endpoints for the damage were: lethality, anemia, glomerular filtration rate, effective renal flow, and histology. Results: We found that: (1) There was a threshold volume for radiation damage; injury did not occur if the volume irradiated was ≤ 1/2V, depending on the endpoints. (2) Median survival times did not depend on the dose when a small volume (i.e., 1/4V or 1/2V) was irradiated. (3) The LD 50 (and the 95% confidence limits) at 450 days were 11.35 (8.08 to 12.13) Gy for 1V, 12.38 (11.08 to 13.40) Gy for 3/4V, 21.16 (17.21 to 26.56) Gy for 1/2V, and 28.80 (21.11 to 65.00) Gy for 1/4V. (4) The ED 50 for animals with hematocrit level ≤0.36 at 365 days was 10.98 (4.96 to 13.67) Gy for 1.0V, and 13.82 (6.16 to 17.97) Gy for 3/4V. For 1/2V, only the 80% confidence limits could be derived, giving ED 50 +40.14 (27.98 to ∞) Gy. (5) The results for all other endpoints were similar to those for hematocrit. (6) The dose response was the same whether to half of each kidney or one whole kidney was irradiated. (7) While the threshold volume for radiation injury

  5. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2016-01-01

    Full Text Available Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ-induced diabetic rat kidney. At the end of the experimental period (28 days, we found that lycopene markedly decreased the malondialdehide (MDA levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

  6. Insulin degradation products from perfused rat kidney

    International Nuclear Information System (INIS)

    Duckworth, W.C.; Hamel, F.G.; Liepnieks, J.; Peavy, D.; Frank, B.; Rabkin, R.

    1989-01-01

    The kidney is a major site for insulin metabolism, but the enzymes involved and the products generated have not been established. To examine the products, we have perfused rat kidneys with insulin specifically iodinated on either the A14 or the B26 tyrosine. Labeled material from both the perfusate and kidney extract was examined by Sephadex G50 and high-performance liquid chromatography (HPLC). In perfusate from a filtering kidney, 22% of the insulin-sized material was not intact insulin on HPLC. With the nonfiltering kidney, 10.6% was not intact insulin. Labeled material from HPLC was sulfitolyzed and reinjected on HPLC. By use of 125 I-iodo(A14)-insulin, almost all the degradation products contained an intact A-chain. By use of 125 I-iodo(B26)-insulin, several different B-chain-cleaved products were obtained. The material extracted from the perfused kidney was different from perfusate products but similar to intracellular products from hepatocytes, suggesting that cellular metabolism by kidney and liver are similar. The major intracellular product had characteristics consistent with a cleavage between the B16 and B17 amino acids. This product and several of the perfusate products are also produced by insulin protease suggesting that this enzyme is involved in the degradation of insulin by kidney

  7. Autoradiographic localization of benzodiazepine receptors in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Beaumont, K.; Healy, D.P.; Fanestil, D.D.

    1984-11-01

    The localization of benzodiazepine (BZD) receptors in the rat kidney was studied by autoradiography after in vitro labeling of kidney slices with flunitrazepam. The affinity, density, and rank order of displacement of (/sup 3/H)-flunitrazepam by several BZDs (RO 5-4864 > diazepam > clonazepam) demonstrated that binding was to BZD receptors of the peripheral type. In autoradiograms obtained with tritium-sensitive film, a high density of silver grains was obtained in the outer medulla, with lower densities in the cortex. Binding was absent from the inner medulla (papilla). In higher resolution autoradiograms obtained with an emulsion-coated cover slip procedure, silver grains were seen to be concentrated over a tubular element in both outer medulla and cortex, identifiable by morphology and distribution as the thick ascending limb of the loop of Henle and the distal convoluted tubule. The identity of the labeled tubules was confirmed by immunofluorescent localization in adjacent slices of Tamm-Horsfall protein, a specific marker for these segments of tubules. Investigation of the effects of peripherally specific BZDs such as RO 5-4864 on distal tubule function is indicated.

  8. Effect of rifampicin on the kidney of albino rats | Peters | Journal of ...

    African Journals Online (AJOL)

    The study was designed to investigate the effect of rifampicin on the kidney biomarkers and histopathology of kidney of albino rats. 42 albino rats were used and rifampicin was administered at 1.10mg/120gBW and 0.55mg/120gBW for intervals of 20, 40 and 60days.Animals were sacrificed 24 hours after the last day of ...

  9. Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

    Science.gov (United States)

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2018-03-01

    Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

  10. The impact of gallic acid on the methotrexate-induced kidney damage in rats

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    Halil Asci

    2017-10-01

    Full Text Available Prolonged use of an antineoplastic agent methotrexate (MTX, can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA. Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA, tumor necrosis factor alpha (TNF-α, prostaglandin E2 (PGE-2 and C-reactive protein (CRP in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities.

  11. Protein-Based Urine Test Predicts Kidney Transplant Outcomes

    Science.gov (United States)

    ... News Releases News Release Thursday, August 22, 2013 Protein-based urine test predicts kidney transplant outcomes NIH- ... supporting development of noninvasive tests. Levels of a protein in the urine of kidney transplant recipients can ...

  12. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  13. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  14. Characterization with /sup 3/H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, T; Kuruma, I [Nippon Roche Research Center, Kanagawa (Japan)

    1980-12-01

    The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of /sup 3/H-haloperidol binding. Binding of /sup 3/H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the /sup 3/H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum.

  15. Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

    Science.gov (United States)

    Yang, Ming; Liu, Changjin; Jiang, Jian; Zuo, Guowei; Lin, Xuemei; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-05-27

    The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. The present results

  16. Epidermal growth factor receptor-induced activato protein 1 activity controls density-dependent growht inhibition in normal rat kidney fibroblasts.

    NARCIS (Netherlands)

    Hornberg, J.J.; Dekker, H.; Peters, P.H.J.; Langerak, P.; Westerhoff, H.V.; Lankelma, J.; Zoelen, E.J.J.

    2006-01-01

    Density-dependent growth inhibition secures tissue homeostasis. Dysfunction of the mechanisms, which regulate this type of growth control is a major cause of neoplasia. In confluent normal rat kidney (NRK) fibroblasts, epidermal growth factor (EGF) receptor levels decline, ultimately rendering these

  17. The Obesogenic Potency of Various High-Caloric Diet Compositions in Male Rats, and Their Effects on Expression of Liver and Kidney Proteins Involved in Drug Elimination.

    Science.gov (United States)

    Abdussalam, Ali; Elshenawy, Osama H; Bin Jardan, Yousef A; El-Kadi, Ayman O S; Brocks, Dion R

    2017-06-01

    Obesity is caused by a number of factors including heredity, lack of exercise, and poor diet. Diets rich in fats and carbohydrates are the common culprits leading to obesity. Here we studied the effects of these components on proteins involved in drug disposition. Male rats were given a normal diet (lean controls) or one rich in fats, carbohydrates (as high-fructose corn syrup equivalent) or in combination. After 14 weeks, plasma biochemistry, liver and kidney mRNA and protein for selected cytochrome P450 (CYP) and transporters were determined. Significant increases in body and perinephric fat weight were noted in each of the high-calorie diet-fed groups, with increases being higher in those given high-fat diets. Increases in the protein of CYP3A1/2 and CYP2C11 were seen in liver in high-fat-fed rats. No changes were seen for CYP1A1 at the level of mRNA or protein. For transporters, decreases in expressions of Oct1/2 and Mate1 were seen, with no change in Mdr1. The results showed similarity to earlier assessments of genetically prone rats and suggested that diet-induced obesity has the potential to lead to decreases in the clearance of drugs acting as substrates for CYP 3A, 2C11, and organic cation transport. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jianmin Ran

    2014-01-01

    Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

  19. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

    Directory of Open Access Journals (Sweden)

    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  20. Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

    Science.gov (United States)

    Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

    2015-09-08

    Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

    Science.gov (United States)

    Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

    2012-08-01

    While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, "omics" methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl2-treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl2. These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

  2. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

    International Nuclear Information System (INIS)

    Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

    2012-01-01

    While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, “omics” methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl 2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl 2 -treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl 2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl 2 . These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

  3. Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

    Science.gov (United States)

    Engbersen, R; Moons, M M; Wouterse, A C; Dijkman, H B; Kramers, C; Smits, P; Russel, F G

    2000-08-01

    Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with glibenclamide (10 microM). In agreement with the effect on functional parameters, ultrastructural analysis of proximal tubules showed increased brush border preservation in tolbutamide treated kidneys compared to untreated hypoxic kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce hypoxic damage to proximal tubules in the isolated perfused rat kidney when applied in the appropriate concentrations.

  4. Thiazide diuretic drug receptors in rat kidney: Identification with [3H]metolazone

    International Nuclear Information System (INIS)

    Beaumont, K.; Vaughn, D.A.; Fanestil, D.D.

    1988-01-01

    Thiazides and related diuretics inhibit NaCl reabsorption in the distal tubule through an unknown mechanism. The authors report here that [ 3 H]metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter. [ 3 H]Metolazone bound with high affinity to a site with a density of 0.717 pmol/mg of protein in kidney membranes. The binding site was localized to the renal cortex, with little or not binding in other kidney regions and 11 other tissues. The affinities of thiazide-type diuretics for this binding site were significantly correlated with their clinical potency. Halide anions specifically inhibited high-affinity binding of [ 3 H]metolazone to this site. [ 3 ]Metolazone also bound with lower affinity to sites present in kidney as well as in liver, testis, lung, brain, heart, and other tissues. Calcium antagonists and certain smooth muscle relaxants had K i values of 0.6-10 μM for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested. Properties of the high-affinity [ 3 H]metolazone binding site are consistent with its identity as the receptor for thiazide-type diuretics

  5. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Anita K. Patlolla

    2016-03-01

    Full Text Available Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications.

  6. Mechanism of petroleum-induced sex-specific protein droplet nephropathy and renal cell proliferation in Fischer-344 rats: relevance to humans

    International Nuclear Information System (INIS)

    Charbonneau, M.; Short, B.G.; Lock, E.A.; Swenberg, J.A.

    1987-01-01

    Acute inhalation exposure of male rats to vaporized unleaded gasoline causes a protein droplet-nephropathy syndrome, whereas chronic exposure produces a significant increase renal tumor incidence. The renal lesions produced by chronic or acute exposure to UG have not been observed in kidneys of female rats, or either sex of mice. The assessment of the genotoxic properties of unleaded gasoline by a battery of tests has shown that unleaded gasoline is non-genotoxic. A 21-day histoautoradiographic study in male rats exposed to inhaled unleaded gasoline or gavaged with 2,2,4-trimethylpentane (TMP), a nephrotoxic component of unleaded gasoline selected as a model compound, has shown a dose-dependent increase in cell proliferation specifically in the proximal tubule, segments that have an increased protein droplet formation. A disposition study in male and female rats showed that after a single dose of [ 14 C]-TMP, TMP-derived radiolabel was retained in kidneys of male rats. An increase in the renal α2u-globulin concentration was concomitantly observed in male but not female rats

  7. Dopamine1 receptors in rat kidneys identified with 125I-Sch 23982

    International Nuclear Information System (INIS)

    Felder, R.A.; Jose, P.A.

    1988-01-01

    Dopamine1 receptors were studied in rat kidney using the selective dopamine1 antagonist 125I-labeled Sch 23982. The specific binding of 125I-Sch 23982 (defined by 5 microM Sch 23390) to renal cortical homogenates incubated at room temperature was rapid, saturable with time and ligand concentration, and reversible. Analysis of Rosenthal plots revealed a single class of receptors with an apparent dissociation constant of 12.2 +/- 1.9 nM and maximum receptor density of 1.03 +/- 0.15 pmol/mg protein (n = 6). However, competition experiments with the dopamine1 antagonist Sch 23390 revealed a low- and high-affinity binding site with inhibition constants of 1 x 10(-6) and 1 x 10(-8) M, respectively. The competition experiments were also indicative of dopamine1 receptors with stereoselectivity noted for dopamine1 but not for dopamine2 antagonists. The inhibition constants for dopamine1 antagonists and agonists were two orders of magnitude greater in renal cortical than striatal homogenates. Different buffers affected striatal but not renal cortical binding. Autoradiographic studies revealed 125I-Sch 23982 binding in renal cortical but not medullary tissue. These studies confirm the presence of dopamine1 receptors in the cortex of the rat kidney

  8. Dietary management of chronic kidney disease: protein restriction and beyond.

    Science.gov (United States)

    Goraya, Nimrit; Wesson, Donald E

    2012-11-01

    More kidney protective strategies are needed to reduce the burden of complete kidney failure from chronic kidney disease (CKD). Clinicians sometimes use protein restriction as kidney protection despite its demonstrated lack of effectiveness in the only large-scale study. Small-scale studies support that dietary acid reduction is kidney-protective, including when done with base-inducing foods like fruits and vegetables. We review these studies in light of current kidney-protective recommendations. Animal models of CKD show that acid-inducing dietary protein exacerbates and base-inducing protein ameliorates nephropathy progression, and that increased intake of acid-inducing but not base-inducing dietary protein exacerbates progression. Clinical studies show that dietary acid reduction with Na-based alkali reduces kidney injury and slows nephropathy progression in patients with CKD and reduced glomerular filtration rate (GFR); base-inducing fruits and vegetables reduce kidney injury in patients with reduced GFR; and base-inducing fruits and vegetables improve metabolic acidosis in CKD. Protein type rather than amount might more importantly affect nephropathy progression. Base-inducing foods might be another way to reduce dietary acid, a strategy shown in small studies to slow nephropathy progression. Further studies will determine if CKD patients should be given base-inducing food as part of their management.

  9. Biochemical changes in the liver, kidney and serum of rat following ...

    African Journals Online (AJOL)

    The effect of repeated administration of cimetidine, an antiulcer agent, twice daily for 7days on the phosphatase (acid and alkaline) and some function indices of rat liver and kidney was investigated. Sixty-four white albino rats were randomly grouped into two, A and B. Group A which consisted of 32 rats served as the ...

  10. The beneficial effect of cynodon dactylon fractions on ethylene glycol-induced kidney calculi in rats.

    Science.gov (United States)

    Khajavi Rad, Abolfazl; Hadjzadeh, Mousa-Al-Reza; Rajaei, Ziba; Mohammadian, Nema; Valiollahi, Saleh; Sonei, Mehdi

    2011-01-01

    To assess the beneficial effect of different fractions of Cynodon dactylon (C. dactylon) on ethylene glycol-induced kidney calculi in rats. Male Wistar rats were randomly divided into control, ethylene glycol, curative, and preventive groups. The control group received tap drinking water for 35 days. Ethylene glycol, curative, and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation. Preventive and curative subjects also received different fractions of C. dactylon extract in drinking water at 12.8 mg/kg, since day 0 and day 14, respectively. After 35 days, the kidneys were removed and examined for histopathological findings and counting the CaOx deposits in 50 microscopic fields. In curative protocol, treatment of rats with C. dactylon N-butanol fraction and N-butanol phase remnant significantly reduced the number of the kidney CaOx deposits compared to ethylene glycol group. In preventive protocol, treatment of rats with C. dactylon ethyl acetate fraction significantly decreased the number of CaOx deposits compared to ethylene glycol group. Fractions of C. dactylon showed a beneficial effect on preventing and eliminating CaOx deposition in the rat kidney. These results provide a scientific rational for preventive and treatment roles of C. dactylon in human kidney stone disease.

  11. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Dinesh Babu Jestadi

    2014-01-01

    Full Text Available The present study evaluates the effects of short term (15 days exposure of low dose (300 μg kg−1 of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine on antioxidant status and markers of liver and kidney damage in normal (nondiabetic and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.

  12. The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

    Science.gov (United States)

    Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

    2015-06-01

    This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

  13. Simultaneous analysis of proteome, phospho- and glycoproteome of rat kidney tissue with electrostatic repulsion hydrophilic interaction chromatography.

    Directory of Open Access Journals (Sweden)

    Piliang Hao

    Full Text Available Protein post-translational modifications (PTMs are regulated separately from protein expression levels. Thus, simultaneous characterization of the proteome and its PTMs is pivotal to an understanding of protein regulation, function and activity. However, concurrent analysis of the proteome and its PTMs by mass spectrometry is a challenging task because the peptides bearing PTMs are present in sub-stoichiometric amounts and their ionization is often suppressed by unmodified peptides of high abundance. We describe here a method for concurrent analysis of phosphopeptides, glycopeptides and unmodified peptides in a tryptic digest of rat kidney tissue with a sequence of ERLIC and RP-LC-MS/MS in a single experimental run, thereby avoiding inter-experimental variation. Optimization of loading solvents and elution gradients permitted ERLIC to be performed with totally volatile solvents. Two SCX and four ERLIC gradients were compared in details, and one ERLIC gradient was found to perform the best, which identified 2929 proteins, 583 phosphorylation sites in 338 phosphoproteins and 722 N-glycosylation sites in 387 glycoproteins from rat kidney tissue. Two hundred low-abundance proteins with important functions were identified only from the glyco- or phospho-subproteomes, reflecting the importance of the enrichment and separation of modified peptides by ERLIC. In addition, this strategy enables identification of unmodified and corresponding modified peptides (partial phosphorylation and N-glycosylation from the same protein. Interestingly, partially modified proteins tend to occur on proteins involved in transport. Moreover, some membrane or extracellular proteins, such as versican core protein and fibronectin, were found to have both phosphorylation and N-glycosylation, which may permit an assessment of the potential for cross talk between these two vital PTMs and their roles in regulation.

  14. High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney

    Directory of Open Access Journals (Sweden)

    Kerstin Stemmer

    2012-09-01

    Obesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens or partially resistant (DIOres to DIO to investigate the impact of body adiposity versus dietary nutrient overload in the development of renal preneoplasia and activation of tumor-promoting signaling pathways. Our data clearly show a correlation between body adiposity, the severity of nephropathy, and the total number and incidence of preneoplastic renal lesions. However, similar plasma triglyceride, plasma free fatty acid and renal triglyceride levels were found in chow-fed, DIOres and DIOsens rats, suggesting that lipotoxicity is not a critical contributor to the renal pathology. Obesity-related nephropathy was further associated with regenerative cell proliferation, monocyte infiltration and higher renal expression of monocyte chemotactic protein-1 (MCP-1, interleukin (IL-6, IL-6 receptor and leptin receptor. Accordingly, we observed increased signal transducer and activator of transcription 3 (STAT3 and mammalian target of rapamycin (mTOR phosphorylation in tubules with preneoplastic phenotypes. In summary, our results demonstrate that high body adiposity induces an inflammatory and proliferative microenvironment in rat kidneys that promotes the development of preneoplastic lesions, potentially via activation of the STAT3 and mTOR signaling pathways.

  15. Genistein attenuates ischemia/reperfusion injury in rat kidneys via ...

    African Journals Online (AJOL)

    kidneys via enhancement of antioxidant defense mechanisms: Activation ... Renal function, total oxidant capacity and total antioxidant status in serum were evaluated in the rats. ..... Erel O. Novel automated method to measure total antioxidant ...

  16. Evaluation of selected parameters of rat liver and kidney function ...

    African Journals Online (AJOL)

    The effects of administration of yohimbine, an aphrodisiac on some functional parameters of rat liver and kidney were investigated. White male albino rats weighing between 200-250g were grouped into two such that one group was orally administered with 14mg/kg body weight on daily basis for 15days while the control ...

  17. Muscle and liver protein synthesis in growing rats fed diets containing raw legumes as the main source of protein

    International Nuclear Information System (INIS)

    Goena, M.; Santidrian, S.; Cuevillas, F.; Larralde, J.

    1986-01-01

    Although legumes are widely used as protein sources, their effects on protein metabolism remain quite unexplored. The authors have measured the rates of gastrocnemius muscle and liver protein synthesis in growing rats fed ad libitum over periods of 12 days on diets containing raw field bean (Vicia faba L.), raw kidney bean (Phaseolus vulgaris L.), and raw bitter vetch (Vicia ervilia L.) as the major sources of protein. Diets were isocaloric and contained about 12% protein. Protein synthesis was evaluated by the constant-intravenous-infusion method, using L-/ 14 C/-tyrosine, as well as by the determination of the RNA-activity (g of newly synthesized protein/day/g RNA). Results showed that, as compared to well-fed control animals, those fed the raw legume diets exhibited a marked reduction in the rate of growth with no changes in the amount of food intake (per 100 g b.wt.). These changes were accompanied by a significant reduction in the rate of muscle protein synthesis in all legume-treated rats, being this reduction greater in the animals fed the Ph. vulgaris and V. ervilia diets. Liver protein synthesis was slightly higher in the rats fed the V. faba and V. ervilia diets, and smaller in the Ph. vulgaris-fed rats. It is suggested that both sulfur amino acid deficiency and the presence of different anti-nutritive factors in raw legumes may account for these effects

  18. Dynamic computed tomography (CT) in the rat kidney and application to acute renal failure models

    International Nuclear Information System (INIS)

    Ishikawa, Isao; Saito, Tadashi; Ishii, Hirofumi; Bansho, Junichi; Koyama, Yukinori; Tobita, Akira

    1995-01-01

    Renal dynamic CT scanning is suitable for determining the excretion of contrast medium in the cortex and medulla of the kidney, which is valuable for understanding the pathogenesis of disease processes in various conditions. This form of scanning would be convenient for use, if a method of application to the rat kidney were available. Therefore, we developed a method of applying renal dynamic CT to rats and evaluated the cortical and medullary curves, e.g., the corticomedullary junction time which is correlated to creatinine clearance, in various rat models of acute renal failure. The rat was placed in a 10deg oblique position and a bilateral hilar slice was obtained before and 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160 and 180 sec after administering 0.5 ml of contrast medium using Somatom DR. The width of the slice was 4 mm and the scan time was 3 sec. The corticomedullary junction time in normal rats was 23.0±10.5 sec, the peak value of the cortical curve was 286.3±76.7 Hounsfield Unit (HU) and the peak value of the medullary curve was 390.1±66.2 HU. Corticomedullary junction time after exposure of the kidney was prolonged compared to that of the unexposed kidney. In rats with acute renal failure, the excretion pattern of contrast medium was similar in both the glycerol- and HgCl2-induced acute renal failure models. The peak values of the cortical curve were maintained three hours after a clamp was placed at the hilar region of the kidney for one hour, and the peak values of the medullary curve were maintained during the administration of 10μg/kg/min of angiotensin II. Dynamic CT curves in the acute renal failure models examined were slightly different from those in human acute renal failure. These results suggest that rats do not provide an ideal model for human acute renal failure. However, the application of dynamic CT to the rat kidney models was valuable for estimating the pathogenesis of various human kidney diseases. (author)

  19. Single Silver Nanoparticle Instillation Induced Early and Persisting Moderate Cortical Damage in Rat Kidneys

    Directory of Open Access Journals (Sweden)

    Elisa Roda

    2017-10-01

    Full Text Available The potential toxic effects of silver nanoparticles (AgNPs, administered by a single intratracheal instillation (i.t, was assessed in a rat model using commercial physico-chemical characterized nanosilver. Histopathological changes, overall toxic response and oxidative stress (kidney and plasma protein carbonylation, paralleled by ultrastructural observations (TEM, were evaluated to examine renal responses 7 and 28 days after i.t. application of a low AgNP dose (50 µg/rat, compared to an equivalent dose of ionic silver (7 µg AgNO3/rat. The AgNPs caused moderate renal histopathological and ultrastructural alteration, in a region-specific manner, being the cortex the most affected area. Notably, the bulk AgNO3, caused similar adverse effects with a slightly more marked extent, also triggering apoptotic phenomena. Specifically, 7 days after exposure to both AgNPs and AgNO3, dilatation of the intercapillary and peripheral Bowman’s space was observed, together with glomerular shrinkage. At day 28, these effects still persisted after both treatments, accompanied by an additional injury involving the vascular component of the mesangium, with interstitial micro-hemorrhages. Neither AgNPs nor AgNO3 induced oxidative stress effects in kidneys and plasma, at either time point. The AgNP-induced moderate renal effects indicate that, despite their benefits, novel AgNPs employed in consumer products need exhaustive investigation to ensure public health safety.

  20. Comparison of 3 kidney injury multiplex panels in rats.

    Science.gov (United States)

    John-Baptiste, Annette; Vitsky, Allison; Sace, Frederick; Zong, Qing; Ko, Mira; Yafawi, Rolla; Liu, Ling

    2012-01-01

    Kidney injury biomarkers have been utilized by pharmaceutical companies as a means to assess the potential of candidate drugs to induce nephrotoxicity. Multiple platforms and assay methods exist, but the comparison of these methods has not been described. Millipore's Kidney Toxicity panel, EMD/Novagen's Widescreen Kidney Toxicity panel, and Meso Scales Kidney Injury panel were selected based on published information. Kidney injury molecule 1, cystatin C, clusterin, and osteopontin were the 4 biomarkers common among all kits tested and the focus of this study. Rats were treated with a low and high dose of para-aminophenol, a known nephrotoxicant, and urine samples were collected and analyzed on the Bio-Plex 200 or MSD's Sector Imager 6000, according to manufacturers specifications. Comparatively, of the 3 kits, Millipore was the most consistent in detecting elevations of 3 out of the 4 biomarkers at both dose levels and indicated time points.

  1. Histopathological effects of doxorubicin on kidneys in rats

    Directory of Open Access Journals (Sweden)

    I.A. Ali

    2014-06-01

    Full Text Available The aim of this study was to investigate the histolopathological effect of doxorubicin on rat kidney tissue. The drug was administrated by rats at the dose of (1, 2, 3, 4, 5 mg/kg intrapertonial every (84 hr for the three weeks and the doses of (1, 2, 3 mg/kg intrapertonial every 84 hrs for six weeks. The animals were scarified after 48 hr. of last injection. The study revealed congestion, thrombus, blood vessels hemorrhage, vaculation in the cells of glomerular tuft and tubular, tubuo-interstitial degeneration, tubular casts. The injury score revealed significantly increasing in the degree of injury in glomerules in the animals that received 5 mg/kg of doxorubicin for three weeks and also significantly increasing in the degree of injury in glomerules of the animals that received 3 mg/kg of doxorubicin for six weeks as compared with control animals. We concluded that the doxorubicin has histopathological effect on kidney.

  2. Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Masakazu Yamaoka

    Full Text Available Free heme, a pro-oxidant released from myoglobin, is thought to contribute to the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI, because renal overexpression of heme oxygenase-1 (HO-1, the rate-limiting enzyme in heme catabolism, confers protection against RM-AKI. BTB and CNC homology 1 (Bach1 is a heme-responsive transcription factor that represses HO-1. Here, we examined the changes with time in the gene expression of Bach1, HO-1, and δ-aminolevulinate synthase (ALAS1, a heme biosynthetic enzyme in the rat kidney using an RM-AKI model induced by the injection of 50% glycerol (10 mL/kg body weight into bilateral limbs. We also examined the protein expression of Bach1 in the nucleus and cytosol, and HO-1 in the rat kidney. Glycerol treatment induced significant elevation of serum creatinine kinase and aspartate aminotransferase levels followed by the marked elevation of serum blood urea nitrogen and creatinine levels, which caused serious damage to renal tubules. Following glycerol treatment, HO-1 mRNA and protein levels were significantly up-regulated, while ALAS1 mRNA expression was down-regulated, suggesting an increase in the free renal heme concentration. The Bach1 mRNA level was drastically increased 3 h after glycerol treatment, and the increased level was maintained for 12 h. Nuclear Bach1 protein levels were significantly decreased 3 h after treatment. Conversely, cytosolic Bach1 protein levels abruptly increased after 6 h. In conclusion, we demonstrate the dynamic changes in Bach1 expression in a rat model of RM-AKI. Our findings suggest that the increase in Bach1 mRNA and cytosolic Bach1 protein expression may reflect de novo Bach1 protein synthesis to compensate for the depletion of nuclear Bach1 protein caused by the induction of HO-1 by free heme.

  3. Effects of ultraviolet radiation on mole rats kidney: A histopathologic and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Hüseyin Türker

    2014-04-01

    Full Text Available The purpose of this study was to realize the ultrastructural effects of ultraviolet radiation on the kidney tissue cells of mole rats (Spalax leucodon. The mole rats of 180–200 g body weight were divided into the control and radiation-trial groups. The control group was not given any radiation. The other groups were irradiated with artificially produced UVC radiation for 14, 28 and 60 days. The kidney tissue samples were prepared at the end of experiments and analyzed by the light and electron microscope. Several effects were observed in the kidney tissues cells analyzed in accordance with the dose magnitude of radiation. These results clearly show the detrimental effects of UVC radiation on kidney tissue cells in exposure periods dependent on radiation dose and exposure time.

  4. d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

    International Nuclear Information System (INIS)

    Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.; Caudill, D.; Fey, M.L.

    1989-01-01

    d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of [ 14 C]d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in female rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction

  5. Uranium XAFS analysis of kidney from rats exposed to uranium.

    Science.gov (United States)

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Shimada, Yoshiya; Homma-Takeda, Shino

    2017-03-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III -edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.

  6. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    Science.gov (United States)

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  7. Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

    DEFF Research Database (Denmark)

    Faarup, Poul; von Holstein-Rathlou, Niels-Henrik; Nørgaard, Tove

    2011-01-01

    To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the pr......To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure...... segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries....

  8. Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

    Science.gov (United States)

    Karakose, M; Pinarli, F A; Arslan, M S; Boyuk, G; Boztok, B; Albayrak, A; Ulus, A T; Cakal, E; Delibasi, T

    2016-01-01

    Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. [Intervention effects of Zuoguiwan containing serum on osteoblast through ERK1/2 and Wnt/β-catenin signaling pathway in models with kidney-Yang-deficiency, kidney-Yin-deficiency osteoporosis syndromes].

    Science.gov (United States)

    Zhang, Jian-Hua; Xin, Jing; Fan, Lian-Xia; Yin, Hua

    2017-10-01

    To clarify the effects of Zuoguiwan containing serum on osteoblast proliferation and alkaline phosphatase(ALP) expression and its effects on the expression of β-catenin, ERK1, ERK2 mRNA and protein of osteoblast through ERK1/2, Wnt/β-catenin signaling pathway in models with osteoporosis(OP) kidney-Yang-deficiency, osteoporosis(OP) kidney-Yin-deficiency syndrome. Rat osteoporosis models were established by ovariectomy surgery, and 10 weeks after surgery, hydrocortisone was injected and thyroxine was administered by intragastric administration to establish OP kidney-Yang-deficiency rat model, and OP kidney-Yin-deficiency rat model. Osteoblasts were obtained from 24 h newborn rat skull and were identified by alkaline phosphatase and alizarin red staining. Zuoguiwan containing serum of OP, OP kidney-Yang-deficiency, and OP kidney-Yin-deficiency, as well as the blank serum were used to intervene the osteoblast, and the cells proliferation was detected by MTS. ELISA assay was used to detect ALP expression. RT-PCR assay was used to detect the mRNA expression of ERK1, ERK2, β-catenin and protein expression levels were detected by Western blot. The results showed that Zuoguiwan containing serum in OP kidney-Yin-deficiency model had stronger effect than OP kidney-Yang-deficiency in promoting osteoblast proliferation, ALP expression, osteoblast ERK1/2, Wnt/β-catenin signaling pathway related factors β-catenin, ERK1, ERK2 mRNA and protein expression levels. This was consistent with the TCM theory of "Zuoguiwan nourishes kidney Yin", providing a scientific basis for the clinical and dialectical treatment of osteoporosis. Zuoguiwan could regulate the proliferation and differentiation of bone cells by ERK1/2 and Wnt/β-catenin signaling pathway, which may be one of the mechanisms of Zuoguiwan for the prevention of osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

  10. Visceral organ mass and hepatic protein synthetic capacity in fed and fasted rats

    International Nuclear Information System (INIS)

    Burrin, D.G.; Britton, R.A.; Ferrell, C.L.

    1986-01-01

    Forty-two male rats (avg wt. = 320 g) were used to assess the effect of severe nutrient restriction (72 h fast) on visceral organ mass and hepatic protein synthetic capacity as measured by in vitro incorporation of U- 14 -C-VALINE ( 14 C-VAL) into isolated hepatocytes. Organ weights expressed as a percent of empty body weight for fed vs. fasted rats were; liver (5.21 +/- .54 vs 3.82 +/- .46), kidney (.87 +/- 0.6 vs .89 +/- .05), stomach (.60 +/- .06 vs .61 +/- .06), intestines (3.70 +/- .44 vs 3.41 +/- .37). No differences were observed in in vitro oxygen consumption (15.7 +/- 3.1 vs 16.1 +/- 3.3, umole min -1 g -1 dry tissue) or 14 -C VAL incorporation (4.93 +/- 1.28 vs 4.31 +/- 1.48, dpm min -1 mg -1 dry tissue) for hepatocytes from fed vs. fasted rats. Analysis of perfused liver tissue indicated fed rats had higher protein (152.1 +/- 16.3 vs 136.6 +/- 29.6, mg/g tissue) and RNA (8.81 +/- 1.66 vs 5.97 +/- 1.87, mg/g tissue) with lower DNA (2.19 +/- .31 vs 3.19 +/- .54, mg/g tissue) compared to fasted rats. Protein-nucleic acid ratios suggest liver tissue from fed rats had a greater capacity for protein synthesis compared to fasted rats, however, this was not evident from in vitro hepatocyte 14 -C VAL incorporation estimates. These data indicate that severe nutrient restriction (72 h fast) affects visceral organ mass largely by reduced liver and gut size as well as decreased hepatic protein synthetic capacity

  11. Comparative Study of Experimentally Induced Cancer of the Kidney in Mice and Rats with X-Rays

    Energy Technology Data Exchange (ETDEWEB)

    Maldague, P. [Cancer Institute, University of Louvain (Belgium)

    1969-11-15

    Local irradiation of a kidney in rats and mice results in the development of radiation- induced cancers in the irradiated kidney. The production of these cancers is considerably greater in rats than in mice, and their frequency depends on: (1) The X-ray dose absorbed by the kidney; (2) The latency period which is longer for carcinomas than for sarcomas; and (3) The degree and extent of renal radiation- induced lesions. A study of the relationship between dose and carcinogenic effect has enabled us to define three types of X-ray dose: (a) An ineffective dose of 570 rads at which the inducement of cancer is zero; (b) An optimum dose of 1700 rads at which the frequency of renal tumours is maximal (85%); and (c) Excessive doses between 7000 and 14 000 rads after which the frequency of radiation-induced cancers of the kidney approaches zero. Studies of the latent period have shown that radiation-induced cancers of the kidney in mice do not appear until 790 days after irradiation, whereas in rats the first cancers appear after 280 days. As regards the mechanism of the inducement of renal cancer by radiation, we have been able to establish that cancers of the kidney only develop from visible renal lesions. Radiation-induced cancers have not been observed in rats or mice whose kidneys were morphologically and functionally normal. (author)

  12. The kidneys play an important role in the clearance of rFVIIa in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Appa, Rupa S.; Lykkesfeldt, Jens

    2014-01-01

    study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model. MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance...... of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats. RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared...

  13. Does prolonged pneumoperitoneum affect the kidney? Oxidative stress, stereological and electron microscopy study in a rat model

    Directory of Open Access Journals (Sweden)

    Diogo B. de Souza

    2013-01-01

    Full Text Available Purpose: Pneumoperitoneum (Pp at 12 to 15 mmHg in rats is associated with kidney damage. However, Pp at 8 mmHg is now known to best correlate to working pressures used in humans. Thus the aim of this work was to study the kidney of rats submitted to prolonged Pp at 8 mmHg. Materials and Methods: Rats were divided into a Sham group (n = 14, submitted to anesthesia, and a Pp group (n = 14, submitted to Pp at 8 mmHg, followed by deflation. In both groups, 7 animals were immediately killed and their kidneys were used for oxidative stress analyses. The remaining 7 rats in each group were evaluated after 6 weeks for the number of glomeruli and podocyte morphology. Results: For all analyzed parameters Sham and Pp groups presented no statistical difference. Conclusion: When submitted to adequate Pp pressures (8 mmHg, no kidney damage occurs in rats.

  14. Dynamic renal scintigraphic estimation of deceased donor kidneys in a rat model

    Directory of Open Access Journals (Sweden)

    Huseyin Aydin Mitil

    2017-01-01

    Full Text Available At present a large number of the renal transplantations are being performed from the deceased donors. The success of these transplantations depends on the viability of the deceased donor kidneys. The aim of this study was to investigate the reliability of scintigraphic estimation of function of deceased donor kidneys by comparing the histopathologic and scintigraphic findings. Ten rats were included in the study (2–3 months old, 250–300 g, all male. Control scintigraphy was performed to all the rats by injection of 37 MBq Tc-99m DTPA from the tail vein in a dynamic manner. Brain death of the rats was achieved by inflation of a Fogartys catheter in the cranial cavity. Immediately, after brain death confirmation, dynamic renal scintigraphy was performed with the same parameters of control scintigraphy. In the comparison of scintigraphies obtained in the before and just after brain death period, there was impairment of tubular functions, concentration and excretion functions in the postbrain death period. In the immediate postbrain death period, there was a significant elevation in the glomerular filtration rate and time to maximum concentration values. In the histopathological evaluation of the kidney samples in the postbrain death period, there were definitive findings of tubular impairment. Dynamic renal scintigraphy also demonstrated definite impairment of tubular system and tubular functions in the deceased donor kidneys. This could explain the reason of the increased frequency of acute tubular necrosis seen among deceased donor kidneys.

  15. Metabolism of cysteine and cysteinesulfinate in rat kidney tubules

    International Nuclear Information System (INIS)

    De La Rosa, J.; Stipanuk, M.H.

    1986-01-01

    In studies with rat hepatocytes, hypotaurine plus taurine production accounted for less than 5% of the total amount of cysteine (CYS) catabolized, whereas more than 90% of the metabolized cysteinesulfinate (CSA) was converted to taurine plus hypotaurine. Similar studies have been carried out with kidney tubules isolated from fed rats and incubated with 2 mM [1- 14 C]CYS or 25 mM [1- 14 C]CSA at 37 0 C for up to 40 min. The production of 14 CO 2 from CSA (3.1 +/- 1.3 nmol/sup ./ min -1 /sup ./ mg dry wt -1 ) was equivalent to the accumulation of N in NH 4 + plus glutamate. Substantial oxidation of CYS was observed (16 +/- 11 nmol CO 2 x min -1 x mg dry wt -1 ), but only 12% of the expected amount of N was recovered as NH 4 + plus glutamate. Accumulation of hypotaurine plus taurine was equivalent to 20% of the observed rate of 14 CO 2 production from CSA but accounted for only 2% of the observed rate of 14 CO 2 production from CYS. Addition of unlabeled CSA to incubations with varying levels of CYS had no effect on production of 14 CO 2 . Addition of 2 mM α-ketoglutarate to the incubation mixtures resulted in an increased in 14 CO 2 production from CSA to 290% of the control level but had no effect on CYS oxidation. In agreement with the authors findings for rat hepatocytes, these data suggest that most metabolism of CYS by the rat kidney tubule occurs by a CSA-independent pathway. However, in contrast to the metabolism of CSA almost entirely to taurine in the hepatocyte, kidney tubules appeared to metabolize CSA primarily by the transamination pathway

  16. Leucine and protein metabolism in obese Zucker rats.

    Directory of Open Access Journals (Sweden)

    Pengxiang She

    Full Text Available Branched-chain amino acids (BCAAs are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA dehydrogenase complex (BCKDC activities. Male obese Zucker rats (11-weeks old had increased body weight (BW, 53%, liver (107% and fat (∼300%, but lower plantaris and gastrocnemius masses (-21-24%. Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%, leucine (Leu turnover and proteolysis [35% per g fat free mass (FFM, urinary markers of proteolysis: 3-methylhistidine (183% and 4-hydroxyproline (766%] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%. A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected, gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418% than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein

  17. Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein

    International Nuclear Information System (INIS)

    Johnson, W.T.; Canfield, W.K.

    1985-01-01

    65 Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65 Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats

  18. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats.

    Science.gov (United States)

    Ohno, Kouhei; Kuno, Atsushi; Murase, Hiromichi; Muratsubaki, Shingo; Miki, Takayuki; Tanno, Masaya; Yano, Toshiyuki; Ishikawa, Satoko; Yamashita, Tomohisa; Miura, Tetsuji

    2017-12-01

    Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3- and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-α, chemokine (C-C motif) ligand 2, and transforming growth factor-β 1 and also with activation of p38 MAPK, JNK, and NF-κB. Cu-CPT22, a TLR1/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-κB, whereas NGAL levels and IL-6 and TNF-α expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1/TLR2-mediated signaling mediates KIM-1 upregulation after MI. NEW & NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1/TLR2

  19. Expression of phosphorylated extracellular signal-regulated kinase in rat kidneys exposed to high +Gz

    Directory of Open Access Journals (Sweden)

    Hyun-Soo Kim

    2012-11-01

    Full Text Available Exposure to high gravitational acceleration forces acting along the body axis from the head to the feet (+Gz severely reduces blood flow to the visceral organs, including the kidneys. Extracellular signal-regulated kinase (ERK figures predominantly in mediating kidney cell responses to a wide variety of stress-related stimuli. Though previous studies have shown the activation of ERK in some experimental models, the regulation of ERK associated with +Gz exposure has not yet been investigated. The aim of this study was to examine the effect of high +Gz exposure on ERK activation in the kidneys. Using a small animal centrifuge, eight male Sprague-Dawley rats were exposed to +10Gz or +13Gz three times for 3 minutes each. The bilateral kidneys were obtained from each rat, and the expression levels of phosphorylated ERK (p-ERK were evaluated using immunohistochemistry. In the control group, the collecting duct epithelium displayed faint cytoplasmic staining with no nuclear staining of p-ERK. By contrast, rats exposed to +10Gz showed strong nuclear staining intensity for p-ERK. In the renal papilla, the epithelial cells of collecting ducts and thin segments of the loop of Henle exhibited strong nuclear immunoreactivity for p-ERK. Rats exposed to +13Gz also showed the same staining intensity and distribution of p-ERK expression as that of rats exposed to +10Gz. This study is the first to describe +Gz exposure-induced alteration in the expression of p-ERK in the kidneys. Our finding suggests that high +Gz exposure leads to the activation of ERK in the renal papilla.

  20. Metallothionein metabolism in the streptozotocin-diabetic rat

    International Nuclear Information System (INIS)

    Chen, M.L.; Failla, M.L.

    1986-01-01

    Earlier reports from their laboratory showed the induction of the insulin-deficient diabetic state in adult rats was associated with an accumulation of zinc, copper, and a metallothionein-like zinc and copper binding protein in the soluble fraction of liver and kidney. Based upon chromatographic and electrophoretic properties, -SH to metal ratio and amino acid composition, they now report that elevated concentrations of metallothioneins (MT)-I and -II are indeed present in diabetic rat liver and kidney cytosol. The relative rates of MT synthesis in tissues from diabetic and control rats were measured by comparing incorporation of 35 S-cysteine into MT vs. total cytoplasmic proteins at 5 h after injection of the precursor. The relative rates of MT synthesis in livers from rats diabetic for 10 d and fed either chow or purified diet containing 13 or 35 ppm copper were 1.4, 2.3 and 2.8 times greater, respectively, than control rats fed the same diets. Higher relative rates of MT synthesis were also observed in kidneys from diabetic rats fed purified diets compared to controls. Maximal relative rates of MT synthesis in diabetic liver and kidney were observed at 4 and 10 d, respectively, after onset of diabetes. The half-lives of cytoplasmic MT in liver and kidney from diabetic (10 d) rats were 1.3 and 2.6 days, respectively; half-lives of MT in control liver and kidney were 5.0 and 2.1 days, respectively

  1. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

    Science.gov (United States)

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-01-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  2. Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study.

    Science.gov (United States)

    Khoshvakhti, Habib; Yurt, K Kübra; Altunkaynak, B Zuhal; Türkmen, Aysın P; Elibol, Ebru; Aydın, Işınsu; Kıvrak, Elfide G; Önger, M Emin; Kaplan, Süleyman

    2015-01-01

    In this study, we aimed to investigate the effect of diclofenac sodium (DS) and melatonin (MEL) on kidney of the prenatally administered rats. Pregnant rats were divided into the control, physiological saline, DS, and DS + MEL groups. All injections were given beginning from the 5th day after mating to the 15th day of the pregnancy. Physical dissector and Cavalieri principle were used to estimate the numerical density and total number of glomeruli and the volumetric parameters of kidney, respectively. Our stereological results indicated that DS application during the pregnancy lead to decrease in the mean volume, numerical density, and total number of the glomeruli (p  0.05). Light microscopic investigation showed congestion in blood vessels and shrinkage of the Bowman's space in the DS group. Moreover, there was degeneration in nephrons including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys of the DS-treated group. However, usage of the MEL with the DS caused preventing of these pathological alterations in the kidney. We suggested that DS might lead to adverse effects in the kidneys of the rats that are prenatally subjected to this drug. Fortunately, these adverse effects can be prevented by the melatonin supplementation.

  3. Regulation of N-nitrosodimethylamine demethylase in rat liver and kidney.

    Science.gov (United States)

    Hong, J Y; Pan, J M; Dong, Z G; Ning, S M; Yang, C S

    1987-11-15

    In previous work, the low Km form of N-nitrosodimethylamine (NDMA) demethylase has been demonstrated to be due to a specific form of cytochrome P-450 (designated as P-450ac) and to be the enzyme required for the metabolic activation of NDMA. The present work deals with the regulation of P-450ac in rat liver during development as well as the mechanism of induction of P-450ac in rat liver and kidney by inducers. NDMA demethylase activity was almost undetectable in the liver of newborn rats, increased after day 4, and remained elevated throughout the first 17 days of the neonatal period. The enhancement of NDMA demethylase activity during development was accompanied by corresponding increases of P-450ac content and P-450ac mRNA levels as determined by Western and slot blot analyses, respectively. No sex differences with respect to this enzyme were observed in the developing rats. Acetone treatment on late-term pregnant rats for 2 days resulted in transplacental inductions of P-450ac and P-450ac mRNA in the newborn rats. Pretreatment of young male rats and adult female rats with acetone or isopropyl alcohol caused increases of NDMA demethylase activity and P-450ac content in the liver but no significant change in the P-450ac mRNA level. These facts suggest the possible existence of a posttranscription regulatory mechanism under these induction conditions. The presence of P-450ac in rat kidney was demonstrated by Western and Northern blot analyses. The renal form of P-450ac seemed to be regulated in a fashion similar to the hepatic P-450ac regarding its response to inducing factors such as fasting and acetone treatment.

  4. Life cycle analysis of kidney gene expression in male F344 rats.

    Directory of Open Access Journals (Sweden)

    Joshua C Kwekel

    Full Text Available Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs. Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

  5. Effects of high-protein diet containing isolated whey protein in rats submitted to resistance training of aquatic jumps.

    Science.gov (United States)

    Avila, Eudes Thiago Pereira; da Rosa Lima, Thiago; Tibana, Ramires Alsamir; de Almeida, Paula Caroline; Fraga, Géssica Alves; de Souza Sena, Mariana; Corona, Luiz Felipe Petusk; Navalta, James Wilfred; Rezaei, Sajjad; Ghayomzadeh, Morteza; Damazo, Amílcar Sabino; Prestes, Jonato; Voltarelli, Fabrício Azevedo

    2018-02-13

    Isolated whey protein (IWP) can decrease body fat compared with other protein sources. The present study verified the effects of high protein diet (HD) containing IWP on several parameters of rats subjected to resistance training (RT). Thirty-two male Wistar rats (60 days of age) were separated into four groups (n = 8/group): sedentary normoproteic (IWP 14%; SN); sedentary hyperproteic (IWP 35%; SH); trained normoproteic (IWP 14%; TN), and trained hyperproteic (WPI 35%; TH). Relative tissue/organ weight (g): perirenal and retroperitoneal adipose tissues were lower in SH and TH compared with SN (no difference to TN); omental and subcutaneous adipose tissues were higher in SN compared with SH. Epididymal adipose tissue was higher in SN compared with other groups. Heart weight was higher in TH compared with TN and SN, but not SH; kidney and liver higher in TH and SH compared with SN and TN; gastrocnemius lower in SN compared with other groups; soleus higher in SH in relation to other groups. The triglycerides levels (mg/dL) was reduced in the TH groups compared with SH, TN, and SN. There were no changes both in the concentrations of adiponectin and leptin and in the protein expression of GLUT-4 and p70 s6k . HD containing WPI improved body composition, increased the weight of the heart, kidneys, liver and gastrocnemius and soleus muscles; however, this diet maintained the normal histomorphology of muscle and liver and, when associated with RT, reduced the serum levels of triglycerides. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

    Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

  7. Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol.

    Science.gov (United States)

    Gomez-Sanchez, Elise P; Ganjam, Venkataseshu; Chen, Yuan Jian; Liu, Ying; Zhou, Ming Yi; Toroslu, Cigdem; Romero, Damian G; Hughson, Michael D; de Rodriguez, Angela; Gomez-Sanchez, Celso E

    2003-08-01

    The 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 (11betaHSD1) enzyme is an NADP+-dependent oxidoreductase, usually reductase, of major glucocorticoids. The NAD+-dependent type 2 (11betaHSD2) enzyme is an oxidase that inactivates cortisol and corticosterone, conferring extrinsic specificity of the mineralocorticoid receptor for aldosterone. We reported that addition of a reducing agent to renal homogenates results in the monomerization of 11betaHSD2 dimers and a significant increase in NAD+-dependent corticosterone conversion. Estrogenic effects on expression, dimerization, and activity of the kidney 11betaHSD1 and -2 enzymes are described herein. Renal 11betaHSD1 mRNA and protein expressions were decreased to very low levels by estradiol (E2) treatment of both intact and castrated male rats; testosterone had no effect. NADP+-dependent enzymatic activity of renal homogenates from E2-treated rats measured under nonreducing conditions was less than that of homogenates from intact animals. Addition of 10 mM DTT to aliquots from these same homogenates abrogated the difference in NADP+-dependent activity between E2-treated and control rats. In contrast, 11betaHSD2 mRNA and protein expressions were significantly increased by E2 treatment. There was a marked increase in the number of juxtamedullary proximal tubules stained by the antibody against 11betaHSD2 after the administration of E2. Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone excreted in the urine nor their ratio differed between E2- and vehicle-treated rats. NAD+-dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11betaHSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers.

  8. Zidovudine therapy: Effect(s) on histology of the kidney of wister rats ...

    African Journals Online (AJOL)

    This study investigated the histo-morphological effect(s) of Zidovudine therapy on the kidney of Wister rats. Fifteen Wistar rats obtained from the Animal house of the College of Medicine, Ambrose Alli University, Ekpoma, Edo State, Nigeria, were used for this study. A three week period of acclimatisation was allowed.

  9. Effect of short-term vs. long-term elevation of dietary protein intake on responsiveness of rat thick ascending limbs to peptide hormones.

    Science.gov (United States)

    Goldstein, David L; Plaga, Kimberly

    2002-10-01

    We compared the renal responses of rats on three diet regimens. Rats received either 8% protein food (low-protein, LP) for 10 weeks following weaning, 8% protein for 9 weeks followed by 1 week on 30% protein (short-term high-protein, SHP), or 30% protein for 10 weeks (high-protein, HP). Kidneys from HP rats were enlarged by approximately 50%, or 20% when corrected for body mass. Most of this hypertrophy resulted from enlargement of the inner stripe of the outer medulla, site of the thick ascending limbs (TAL), and TAL from HP rats were larger in diameter. SHP rats had TAL diameters similar to HP rats, but changes in renal mass or height of renal zones did not reach statistical significance. The activity of adenylyl cyclase (AC) in TAL, measured from the accumulation of cAMP in isolated tubules, increased with dose of both arginine vasopressin (AVP) and glucagon in all rats. However, HP rats had significantly higher hormone-induced AC activity than LP or SHP rats, which were not different from each other. Our results suggest that tubule hypertrophy may precede up-regulation of hormone-sensitive AC activity during the progression of renal response to elevated dietary protein.

  10. Acute effects of organotins on brain, liver and kidney in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

    1985-01-01

    Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

  11. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015

  12. A Study of the Modulating Action of Quercetin on Biochemical and Histological Alterations Induced by Lead Exposure in the Liver and Kidney of Rats.

    Science.gov (United States)

    Mohammed, Ghena M.; Sedky, Azza; Elsawy, Hany

    2017-06-30

    Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i.p. quercetin (50 mg/kg b.w.); (iv) lead and quercetin group received i.p. lead acetate (20 mg/kg b.w.) followed by i.p. quercetin (50 mg/kg b.w.) for 4 weeks. The lead concentrations were determined in the liver and kidney tissues. Liver marker enzymes, bilirubin, albumin, total protein, creatinine, uric acid and urea, were assessed in the serum and light microscopic studies were performed. The results showed that lead acetate administration was associated with an increase in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, total bilirubin, creatinine, uric acid, urea levels. Lead accumulation in kidneys and liver tissues was also found, but were associated with decrease in albumin and total protein in comparison with the respective mean values of the control. Lead acetate caused numerous histological alterations in the liver, including chronic inflammation, bilary hyperplasia, edema, congestion, Kupffer cells hyperplasia and hemosiderosis, and in the kidney, including tubular dilation, atrophy of glomerular tuft, widening of urinary space and mild fibroblast. In contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values and improved structure of liver and kidney with significant decreases in the severity of histopathological changes when compared with the lead acetate group. In conclusion, treatment with quercetin may provide a

  13. Biochemical and histological changes in liver and kidney in male Wistar albino rats following exposure to Solignum®: a permethrincontaining wood preservative

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    Kingsley C. Patrick-Iwuanyanwu

    2014-12-01

    Full Text Available The present investigation was aimed to determine the effect of sub-chronic exposure to Solignum®, a permethrin-containing wood preservative on biochemical and histological changes in liver and kidneys of male Wistar albino rats. Thirty-two male rats were randomly divided into four groups: control and three treatment concentrations containing 8 rats each. The treatment groups were exposed to Solignum® at dose rates of 100, 200 and 400 mg/kg body weight (BW respectively per day orally for four weeks. Data obtained from the study showed a progressive increase in the body weight of rats in control whereas, rats treated with different concentrations (100, 200 and 400 mg/kg BW of Solignum® decreased significantly (≤0.05 especially at the end of the second and fourth week when compared with control. On the other hand, there was a significant decrease in the relative liver weights of rats treated with 100 and 200 mg/kg BW Solignum® while rats treated with 400 mg/kg BW showed a significant increase when compared with control. The relative weight of kidneys in experimental groups increased significantly when compared with control. Biochemical analysis results illustrated that there was a significant increase in marker enzymes namely alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity at the end of the fourth week. Similarly, total bilirubin, serum urea, creatinine and electrolytes (Na+, K+ and Cl- levels increased in a dose dependent manner in treated rats when compared with untreated control group. Serum total protein decreased significantly in experimental rats when compared with control. However, cholesterol and triglycerides showed no significant difference when compared with control. Histopathological examination of hepatocytes in treated rats was characterized by mild periportal inflammatory cells and cytoplasmic degeneration. Furthermore, histopathological examination of rat kidneys revealed inflammatory

  14. Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.

    Science.gov (United States)

    Sun, Yan; Peng, Ping-An; Ma, Yue; Liu, Xiao-Li; Yu, Yi; Jia, Shuo; Xu, Xiao-Han; Wu, Si-Jing; Zhou, Yu-Jie

    2017-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (Pvalsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (PValsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Lycopene Usage as a Treatment for Kidney Dysfunctions Induced by Adriamycin in Rats

    International Nuclear Information System (INIS)

    Mekawy, H.M.S.

    2012-01-01

    Adriamycin is chemically synthesized antibiotic anthracycline and due to the successful action of it as a chemotherapy agent, several strategies have been tried to prevent or attenuate the side effects of adriamycin. Lycopene, a carotenoid naturally occurring in tomatoes, has attracted considerable attention as an antioxidant. Rats were divided into 4 groups; control group, ravaged and injected with vehicles, lycopene group, received lycopene (5 mg/kg body weight/day by gavages) and injected intra peritoneum (ip) with 0.5 ml of vehicle for 7 weeks. Adriamycin group injected with adriamycin (4 doses of ip 4 mg/kg body weight at 3, 4, 5 and 6 weeks) or adriamycin and lycopene group received both lycopen and adriamycin dosage. In adriamycin groups, plasma creatinine, urea and malondialdeyde (MDA) levels were increased significantly, total proteins level was decreased and serum nitric oxide (NO) level was increased significantly. Moreover, blood level of reduced glutathione (GSH) and levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) were reduced significantly. Furthermore, renal MDA and NO concentrations were increased significantly and levels of GSH, SOD, CAT and GSHPx were reduced significantly. Protracted treatment of adriamycin-treated rats with lycopene resulted in a significant modulation in all plasma, serum, blood and renal tested parameters. These results have suggested that lycopene modulated the kidney damage induced by the adriamycin nephrotoxicant in male rats. The mechanisms of lycopene overcome against adriamycin-induced toxicity were proved to be due to inhibition of lipid per oxidation (LP) and GSH depletion. The present study demonstrated a beneficial effect of lycopene treatment against adriamycin-induced kidney disorders by reversing the oxidative stress

  16. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  17. Lithium Impairs Kidney Development and Inhibits Glycogen Synthase Kinase-3β in Collecting Duct Principal Cells

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    level significantly whereas total GSK-3β abundance was unaltered. Li+ treatment increased α-Smooth Muscle Actin (α-SMA) protein level significantly whereas E-cadherin expression was unaltered. In summary, Li+ treatment impairs postnatal development of the kidney cortex and outer medulla and increases pGSK......The postnatal rat kidney is highly susceptible to Lithium (Li+), which leads to significant tissue injury. We hypothesized that Li+ impairs development of the kidney through entry into epithelial cells of the distal nephron, inhibition of Glycogen Synthase Kinase-3β (GSK-3β) through phosphorylation...... on serine9 (pGSK-3β)and subsequent epithelial to mesenchymal dedifferentiation (EMT). GSK-3β immunoreactive protein was associated with collecting ducts in developing and adult human and rat kidney. Total GSK-3β protein abundance was stable in medulla while it decreased in cortex in the postnatal period...

  18. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

    Science.gov (United States)

    Awodele, Olufunsho; Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-12-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (pMangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

  19. Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

    Directory of Open Access Journals (Sweden)

    Wu S

    2014-12-01

    Full Text Available Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC therapy has been considered a promising strategy to cure diabetic nephropathy (DN. However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1 plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1 via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with

  20. Selective Activation of AMPK β1-Containing Isoforms Improves Kidney Function in a Rat Model of Diabetic Nephropathy.

    Science.gov (United States)

    Salatto, Christopher T; Miller, Russell A; Cameron, Kimberly O; Cokorinos, Emily; Reyes, Allan; Ward, Jessica; Calabrese, Matthew F; Kurumbail, Ravi G; Rajamohan, Francis; Kalgutkar, Amit S; Tess, David A; Shavnya, Andre; Genung, Nathan E; Edmonds, David J; Jatkar, Aditi; Maciejewski, Benjamin S; Amaro, Marina; Gandhok, Harmeet; Monetti, Mara; Cialdea, Katherine; Bollinger, Eliza; Kreeger, John M; Coskran, Timothy M; Opsahl, Alan C; Boucher, Germaine G; Birnbaum, Morris J; DaSilva-Jardine, Paul; Rolph, Tim

    2017-05-01

    Diabetic nephropathy remains an area of high unmet medical need, with current therapies that slow down, but do not prevent, the progression of disease. A reduced phosphorylation state of adenosine monophosphate-activated protein kinase (AMPK) has been correlated with diminished kidney function in both humans and animal models of renal disease. Here, we describe the identification of novel, potent, small molecule activators of AMPK that selectively activate AMPK heterotrimers containing the β 1 subunit. After confirming that human and rodent kidney predominately express AMPK β 1, we explore the effects of pharmacological activation of AMPK in the ZSF1 rat model of diabetic nephropathy. Chronic administration of these direct activators elevates the phosphorylation of AMPK in the kidney, without impacting blood glucose levels, and reduces the progression of proteinuria to a greater degree than the current standard of care, angiotensin-converting enzyme inhibitor ramipril. Further analyses of urine biomarkers and kidney tissue gene expression reveal AMPK activation leads to the modulation of multiple pathways implicated in kidney injury, including cellular hypertrophy, fibrosis, and oxidative stress. These results support the need for further investigation into the potential beneficial effects of AMPK activation in kidney disease. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Teng; Tian, Wulin; Liu, Fangning; Xie, Guanghong, E-mail: xiegh@jlu.edu.cn

    2014-05-16

    Highlights: • β-Hydroxybutyrate inhibits paraquat-induced toxicity in rat kidney. • β-Hydroxybutyrate inhibits lipid peroxidation and caspase-mediated apoptosis. • β-Hydroxybutyrate increases the activities of SOD and CAT. • The study describes a novel finding for the renoprotective ability of β-hydroxybutyrate. - Abstract: In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, β-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). β-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury.

  2. Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

    Science.gov (United States)

    Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

    2017-02-01

    Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

  3. Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

    Directory of Open Access Journals (Sweden)

    Xin Wan

    Full Text Available BACKGROUND AND OBJECTIVES: Impaired renal function in atherosclerotic renovascular disease (ARD may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation. METHODS: Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively. RESULTS: Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ. CONCLUSIONS: We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating

  4. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    Directory of Open Access Journals (Sweden)

    Danijela Karanovic

    Full Text Available Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD. Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger or losartan (angiotensin II type 1 receptor blocker treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS, erythrocyte antioxidant enzymes activities and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities, kidney function and structure in spontaneously hypertensive rats (SHR with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v. twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day, tempol (T,100 mg/kg/day or combined T+L treatment (by gavage during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1 protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4 protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2 protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria, pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  5. Increased albumin permeation in eyes, aorta, and kidney of hypertensive rats fed galactose

    International Nuclear Information System (INIS)

    Tilton, R.G.; LaRose, L.; Chang, K.; Weigel, C.J.; Williamson, J.R.

    1986-01-01

    These experiments were undertaken to determine whether ingestion of galactose increases albumin permeation in the vasculature of hypertensive rats. 50% dextrin (control) or 50% galactose diets were fed to unilaterally nephrectomized, male Sprague-Dawley rats weighing 200 g. Hypertension (systolic pressure >175 mmHg) was induced by weekly IM injections of 25 mg/kg DOCA and 1% saline drinking water; 3 months later 125 I-albumin permeation was assessed in whole eyes, aorta and kidneys. 125 I-albumin permeation was significantly increased in all 3 tissues of hypertensive rats (n = 9) vs controls (n = 9): aorta (3.30 +/- 0.19 (SD) vs 2.87 +/- 0.14), eye (3.15 +/- 0.14 vs 2.59 +/- 0.11), and kidney (6.58 +/- 0.63 vs 3.85 +/- 0.50). Albumin permeation was increased still further in hypertensive rats fed the galactose diet (n = 8): aorta (3.75 +/- 0.38), eye (3.82 +/- 0.17), and kidney (10.74 +/- 3.13). Hypertension +/- galactose feeding had no effect on albumin permeation in lung, skin, or brain. These findings indicate that: (1) hypertension increases albumin permeation in vessels affected by diabetic vascular diseases, and 2) hypertension-induced increases in albumin permeation are increased still further by galactose ingestion, presumably mediated by imbalances in polyol/insitol metabolism (analogous to those induced by diabetes) independent of hyperglycemia and/or insulinopenia

  6. Determination of metallic traces in kidneys, livers, lungs and spleens of rats with metallic implants after a long implantation time.

    Science.gov (United States)

    Rubio, Juan Carlos; Garcia-Alonso, Maria Cristina; Alonso, Concepcion; Alobera, Miguel Angel; Clemente, Celia; Munuera, Luis; Escudero, Maria Lorenza

    2008-01-01

    Metallic transfer from implants does not stop at surrounding tissues, and metallic elements may be transferred by proteins to become lodged in organs far from the implant. This work presents an in vivo study of metallic implant corrosion to measure metallic element accumulation in organs located far from the implant, such as kidneys, livers, lungs and spleens. The studied metallic implant materials were CoCr alloy, Ti, and the experimental alloy MA956 coated with alpha-alumina. The implants were inserted in the hind legs of Wistar rats. Analysis for Co, Cr, Ti and Al metallic traces was performed after a long exposure time of 12 months by Inductively Coupled Plasma (ICP) with Mass Spectrometry (MS). According to the results, the highest Cr and Ti concentrations were detected in spleens. Co is mainly found in kidneys, since this element is eliminated via urine. Cr and Ti traces increased significantly in rat organs after the long implantation time. The organs of rats implanted with the alpha-alumina coated experimental MA956 did not present any variation in Al content after 12 months, which means there was no degradation of the alumina layer surface.

  7. The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

    Directory of Open Access Journals (Sweden)

    Benjamin Nnamdi Okolonkwo

    2014-11-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

  8. A β Damages Learning and Memory in Alzheimer's Disease Rats with Kidney-Yang Deficiency

    OpenAIRE

    Qi, Dongmei; Qiao, Yongfa; Zhang, Xin; Yu, Huijuan; Cheng, Bin; Qiao, Haifa

    2012-01-01

    Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal A β 40 and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synapti...

  9. Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

    Science.gov (United States)

    Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

    2015-01-01

    The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P GABA decreased these parameters in female significantly (P GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

  10. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    Uğur Koca

    2013-01-01

    Full Text Available In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis.

  11. Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

    International Nuclear Information System (INIS)

    Mueller-Suur, R.M.; Mueller-Suur, C.

    1989-01-01

    Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

  12. [Glomerular changes in the contralateral kidney in the rat with experimental hydronephrosis].

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    Castillo Bernabéu, R; Gázquez Ortiz, A; Bonillo Morales, A; Sierra Planas, M A; Ocaña Losa, J M; Romanos Lezcano, A

    1985-10-31

    We have studied under optic and electronmicroscopes the alterations of glomeruli in contralateral kidneys of rats with experimental hydronephrosis. Forty-eight Wistar rats, divided into two groups (control and experimental) were used. They were sacrificed 3, 6, 9 and 12 days after ureteral obstruction. There was a slight hypertrophy of glomeruli and hiperplasia of other components accompanied by a increased development of podocytes.

  13. Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats--a stereological study.

    Science.gov (United States)

    Golalipour, Mohammad Jafar; Gharravi, Anneh Mohammad; Ghafari, Sorya; Afshar, Mohammad

    2007-11-01

    The aim of the present study was to investigate the effect of Urtica dioica on Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar rats of 125-175 g divided into control, diabetic and Urtica dioica treatment groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the animals had been sacrified, the kidneys were removed and fixed by formaldehyde, cut horizontally into 1 mm slices and processed, Stained with H and E. Stereological study performed using light microscope and the image projected on a table of olysa software. Cavalieri principle was used to estimate the volume of cortex, medulla and whole kidney. All the grouped data statistically evaluated using Student's t-test, expressed as the Mean +/- SE. Ration of kidney weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were higher then control group (0.42). Ratio of kidney volume/body weight in diabetes (350) and diabetes-extract group (348) were higher then control group (323). Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then control (1.34) and diabetes group (1.33). Glomerular area and diameter and proximal tubule diameter in diabetes-Extract group was higher than control and diabetes groups. This study revealed that Urtica dioica has no effect on renal morphometric indices in induced diabetic rats.

  14. Correlation of diffusion-weighted MRI and gross anatomy of rat kidneys

    International Nuclear Information System (INIS)

    Chen Rongfeng; Wu Xiaomei; Chen Xiaoyan; Deng Yu; Li Xinchun; He Jianxun; Li Huiming

    2011-01-01

    Objective: To investigate the feasibility and accuracy of diffusion-weighted MRI in differentiating the cortico-medullary layers of rat kidneys. Methods: Twelve rats underwent MRI using a 1.5 Tesla system including DWI of various b-values, T1WI and T 2 WI sequences. The MR characteristics and thickness of renal cortico-medullary layers compared to those of the gross anatomical layers. Results: On the longitudinal anatomical sections of the kidneys, four parenchymal layers of cortex (CO), the outer (OS) and inner (IS) stripes of the outer medulla (OM), the inner medulla (IM) and renal pelvis could be clearly recognized. The numbers of layers visible on MRI varied with different pulse sequences. Single layers of cortex and medulla were visible on T 1 WI. CO, OM and IM were delineated on T 2 WI. CO, OS, IS and IM were clearly identified on DWI and ADC maps. DWI was significantly superior to T 1 WI and T 2 WI for displaying the renal parenchymal layers (P 0.05) from the measurements on DWI (CO: 1.39±0.15 mm, OS: 1.01±0.17 mm, IS: 1.11±0.19 mm, IM: 1.06±0.10 mm). Different b-values of DWI did not show significant difference in depiction of the parenchyma (P>0.05). Conclusion: Four parenchymal layers shown on DWI correlated well with gross anatomical structure and may be used in imaging study of rat kidneys. (authors)

  15. Effects of Chronic Exposure to Sodium Arsenate on Kidney of Rats

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    Namdar Yousofvand

    2015-09-01

    Full Text Available Background: In the present study, histopathological effects of chronic exposure to sodium arsenate in drinkable water were studied on a quantity of organs of rat. Methods: Rats were divided into two groups, group I; served as control group, were main-tained on deionized drinkable water for 2 months, and group II; the study group were given 60 g/ml of sodium arsenate in deionized drinkable water for 2 months. Blood and urine samples from two groups of animals were collected under anesthesia and the animals were sacrificed under deep anesthesia (a-chloralose, 100 mg/kg, I.P. Their kidney, liver, aorta, and heart were dissected out and cleaned of surrounding connective tissue. The organs were kept in formaldehyde (10% for histopathologic examination. Serum and urine samples from two groups were collected and analyzed for arsenic level. Total quantity of arsenic in serum and urine of animal was measured through graphic furnace atomic absorption spectrometry (GF-AAS. Results:Examination with light microscopy did not show any visible structural changes in the aorta, myocardium, and liver of chronic arsenic treated animals.However, a significant effect was observed in the kidneys of chronic arsenic treated rats showing distinct changes in proxi-mal tubular cells. There was high concentration of arsenic in serum and urine of arsenic ex-posed animals (group II significantly (P<0.001. Conclusion:Swollen tubular cells in histopathologic study of kidney may suggest toxic effects of arsenic in the body.

  16. Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats

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    Salwa M. K. Almomen

    2017-03-01

    Full Text Available Individuals living with metabolic syndrome (MetS such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD. This study investigated the beneficial effect of whole grape powder (WGP diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4 and downregulation of Txnip (for ROS production in the kidneys. Furthermore, addition of grape extract reduced H2O2-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.

  17. Increased formic acid excretion and the development of kidney toxicity in rats following chronic dosing with trichloroethanol, a major metabolite of trichloroethylene

    International Nuclear Information System (INIS)

    Green, Trevor; Dow, Jacky; Foster, John

    2003-01-01

    The chronic toxicity of trichloroethanol, a major metabolite of trichloroethylene, has been assessed in male Fischer rats (60 per group) given trichloroethanol in drinking water at concentrations of 0, 0.5 and 1.0 g/l for 52 weeks. The rats excreted large amounts of formic acid in urine reaching a maximum after 12 weeks (∼65 mg/24 h at 1 g/l) and thereafter declining to reach an apparent steady state at 40 weeks (15-20 mg/24 h). Urine from treated rats was more acidic throughout the study and urinary methylmalonic acid and plasma N-methyltetrahydrofolate concentrations were increased, indicating an acidosis, vitamin B12 deficiency and impaired folate metabolism, respectively. The rats treated with trichloroethanol developed kidney damage over the duration of the study which was characterised by increased urinary NAG activity, protein excretion (from 4 weeks), increased basophilia, protein accumulation and tubular damage (from 12 to 40 weeks), increased cell replication (at week 28) and evidence in some rats of focal proliferation of abnormal tubules at 52 weeks. It was concluded that trichloroethanol, the major metabolite of trichloroethylene, induced nephrotoxicity in rats as a result of formic acid excretion and acidosis

  18. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

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    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  19. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

    NARCIS (Netherlands)

    Bueters, Ruud R. G.; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P.; Schreuder, Michiel F.

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal

  20. Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

    Science.gov (United States)

    Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

    2011-02-28

    3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis.

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    Xia, Qiang; Liu, Chunxiao; Zheng, Xia

    2018-02-01

    The aim of the present study was to investigate the protective effects of N‑acetylcysteine (NAC) on contrast‑induced acute kidney injury in rats with unilateral hyronephrosis. Eighty‑two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase‑associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl‑2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all Pmodeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl‑2/Bax (all Prelief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl‑2 mRNA and higher ratio of Bcl‑2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl‑2/Bax mRNA.

  2. Effects of Hominis Placenta Aqua-acupuncture on Kidney and Liver Intoxicated by HgCI2 in Rats

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    Lee, Sang-Keel

    2000-12-01

    Full Text Available Objective: This study was perfomled to examine the therapeutic effect of aqua-acupuncture solution of Hominis Placenta(HP on kidney and liver intoxicated by HgCl2 in rats. Methods: 10% and 25% HP aqua-acupuncture were carried out everyday for 8 days on corresponding bilateral loci of Shinsu(BL23 and Kansu(BL18, respectively, after mercuric chloride intoxication in rats. Thereafter BUN, creatinine, GOT, GPT, ALP, -GT, albumin and total bilirubin were measured before intoxication, and at the 4th and the 8th experimental day. Histopathological and immunochemical observation were also carried out. Results: 1. It showed significant decreases of BUN in the group of 10% HP aqua-acupuncture into Shinsu on the 4th experimental day as compared with the control group. 2. It showed significant decreases of creatinine in the group of 10% HP aqua-acupuncture into Shinsu on the 4th and the 8th experimental days as compared with the control group. 3. There were not any significant changes of GOT, GPT, ALP, γ-GT, albumin and total bilirubin in the HP aqua-acupuncture groups compared with the control group. 4. By the histopathological observations on kidney under a light microscope, all the 10% and 25% HP aqua-acupuncture into Shinsu showed the preventive effect on tubulo-interstitial necrosis and muItifocal calcification in tubular lumen respectively compared with the control group. 5. By the histopathological observations on liver under a light mIcroscope, the groups 10% and 25% HP aqua-acupuncture into Kansu did not show any significant changes in the liver compared with the control group. 6. By the immunochemical analysis of heat shock protein(hsp and glucose-regulated protein(grp in rat renal cortex, the expressions of hsp70 and grp78 were decreased in the and HP aqua-acupuncture into Shinsu respectively compared with the control group. Conclusion: These results suggest that Hominis Placenta aqua-acupuncture have an effect on prevention and protection of

  3. Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration

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    Michał Biernacki

    2018-05-01

    In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted.

  4. The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

    Science.gov (United States)

    Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

    2015-01-01

    The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

  5. Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

    Science.gov (United States)

    Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

    2013-10-01

    Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

  6. Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

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    Maryam Salehi

    2016-02-01

    Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

  7. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

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    Yanling Zhang

    Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

  8. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  9. Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate-induced toxicity in rat kidney.

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    Sawada, Stefanie; Oberemm, Axel; Buhrke, Thorsten; Merschenz, Julia; Braeuning, Albert; Lampen, Alfonso

    2016-06-01

    3-Chloropropane-1,2-diol (3-MCPD) and its fatty acid esters are formed during thermal treatment of fat-containing foodstuff in the presence of salt. Toxicological studies indicate a carcinogenic potential of 3-MCPD, pointing to the kidney as the main target organ. It is assumed that the toxicological property of 3-MCPD esters is constituted by the release of 3-MCPD during digestion. In a repeated-dose 28-day oral toxicity study using Wistar rats, animals were treated with equimolar doses of either 3-MCPD (10 mg/kg body weight) or 3-MCPD dipalmitate (53 mg/kg body weight). A lower dose of 3-MCPD dipalmitate (13.3 mg/kg body weight) was also applied. No histopathologically visible toxicity was observed in the study. To address molecular mechanisms leading to toxicity of 3-MCPD and its esters, kidney samples were analyzed by a comparative, two-dimensional gel electrophoresis/mass spectrometry proteomic approach. After either 3-MCPD or 3-MCPD dipalmitate treatment, alterations in proteins related to various metabolic pathways, including carbohydrate, amino acid, and fatty acid metabolism, were detected. These findings confirm and complement previous data on the inhibition of glucose metabolism by 3-MCPD. Altogether, broad overlap of 3-MCPD- and 3-MCPD dipalmitate-induced proteomic changes was observed. Further analyses revealed that the observed induction of glutathione S-transferase pi 1 (Gstp1) occurred at the transcriptional level and was not related to nuclear factor (erythroid-derived 2)-like 2 activation. Overall, the results indicate common mechanisms of toxicity for 3-MCPD and its dipalmitate ester. Furthermore, data suggest Gstp1 as a sensitive marker for early 3-MCPD-induced effects in rat kidney.

  10. CYTOCHROME P450-DEPENDENT METABOLISM OF TRICHLOROETHYLENE IN THE RAT KIDNEY

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    The metabolism of trichloroethylene (Tri) by cytochrome P450 (P450) was studied in microsomes from liver and kidney homogenates and from isolated renal proximal tubular (PT) and distal tubular (DT) cells from male Fischer 344 rats. Chloral hydrate (CH) was the only metabolite con...

  11. Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition.

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    Rehab Hegazy

    Full Text Available Hexavalent chromium (CrVI is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf against potassium dichromate (PDC-induced acute kidney injury (AKI in rats. Beside, because previous studies suggest that interlukin-18 (IL-18 and insulin-like growth factor-1 (IGF-1 play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o. or (300 mg/kg/day, p.o.; the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.. PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB, IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1 levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA, Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through

  12. Effects of 15 Gy 137Cs γ-rays radiation of rat kidneys on bone metabolism

    International Nuclear Information System (INIS)

    Gao Linfeng; Wang Hongfu; Xu Peikang; Xu Aihong; Zhu Feipeng

    2003-01-01

    The work was to observe the effects of γ-rays radiation of rat kidneys on rat bone metabolism. Ten male SD rats aged 6 months were irradiated at their kidneys with 15 Gy 137 Cs γ-rays (0.91 Gy/min) and were raised for 3 months after the radiation. On collecting 24h urine of rats they were sacrificed for serum, kidney, spine, femur and tibia exams. Results show that the γ-ray irradiation could induce the pathological injuries of renal glomeruli, tubules and mesenchyme. Comparing to the control group, significant changes were found in the irradiated group in terms of their blood urea, nitrogen creatinine, urinal β-2 microglobulin, serum Ca and P, urine Ca and P, activity of serum alkaline phosphatase, 1,25 (OH) 2 D 3 , serum PTH, urine PYD/creatinine, bone mineral density (BMD) of lumbar vertebras, mineral mass of No.4 lumbar vertebra, BMD, dehydrated weight and ash weight of right femur. Marked changes were also found in bone trabecula volume, average bone trabecula thick and the ratio of nodes/points, and rate of mineralization deposition. It was concluded that renal dysfunction and metabolic bone disease might occur with the character of accelerated bone turnover and decreased bone mass

  13. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

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    Arianne van Koppen

    Full Text Available Chronic kidney disease (CKD is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance and effective renal plasma flow (PAH clearance were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  14. Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

    International Nuclear Information System (INIS)

    Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

    2016-01-01

    Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

  15. Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis

    Science.gov (United States)

    Sabiu, S.; O'Neill, F. H.

    2016-01-01

    This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction's ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms. PMID:27579048

  16. Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae, Stigma maydis

    Directory of Open Access Journals (Sweden)

    S. Sabiu

    2016-01-01

    Full Text Available This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction’s ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms.

  17. Nephroprotective effects of Colpomenia sinuosa (Derbes & Solier against carbon tetrachloride induced kidney injury in Wistar rats

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    Lekameera Ramarajan

    2012-05-01

    Full Text Available Objective: To establish the protective effect of seaweed Colpomenia sinuosa against carbon tetra chloride (CCl4 induced oxidative stress and resultant dysfunction of rat kidney. Methods: Seven to eight weeks old male Wistar rats (150-220g were exposed to CCl4 (1.5 ml/kg injection then treated with seaweed Colpomenia sinuosa (100 mg/kg body weight in 0.3% CMC solution. Blood was collected at the 5th day of experimental period to estimate the Total count (TC, Hemoglobin (HB, Total protein (TP, Glucose, Albumin, Cholesterol, TGL and Urea. Results: The results shows significantly decreased (P<0.01 level of TC, the cholesterol and urea levels shows significantly increased (P<0.05 in CCl4 treated groups when compared to control groups. These levels were found to be normalized by oral feeding of C. sinuosa. Then the rats were sacrificed and kidneys taken for enzyme analyses and histological examination. In the CCl4 treated group significantly increased activities in TBARS, SOD, CAT, GPX, GSH (P<0.05 when compared to control group. These increased activities were found to near normal in the CCl 4 + C. sinuosa treated group and Seaweed C. sinuosa treated alone group did not change any enzyme activity. Exposure to CCl4 resulted hydrobhic changes in epithelium and Hypercellulartity of glomerulus was seen in the CCl 4 + drug treated group. Conclusions: These results suggest that the nephroprotective effect of C. sinuosa can be attributed to its enhancing effects on antioxidant defense system and lead to prevent the damage by exposure of CCl4 toxicity.

  18. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage

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    Shahrzad Havakhah

    2015-12-01

    Full Text Available Objective(s:There are a few previously reported studies about the effect of Nigella sativa oil on renal ischemia-reperfusion injury (IRI. The aim of the present study was to test the hypothesis whether pre- or post-treatment with N. sativa hydroalcoholic extract (NSE would reduce tissue injury and oxidative damages in a clinically relevant rat model of renal IRI.    Materials and Methods: IRI was induced by clamping of bilateral renal arteries for 40 min fallowed by reperfusion for 180 min. NSE was prepared in a Soxhlet extractor and administrated with doses of 150 mg/kg or 300 mg/kg at 1 hr before ischemia induction (P-150 and 300 or at the beginning of reperfusion phase (T-150 and 300, via jugular catheter intravenously. The kidneys were then removed and subjected to biochemical analysis, comet assay or histopathological examination. Results: The kidneys of untreated IRI rats had a higher histopathological score (P

  19. Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling.

    Science.gov (United States)

    Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I

    2015-08-03

    In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na(+)/Ca(2+) exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.

  20. Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex

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    Mei-Ling Hou

    2016-03-01

    Full Text Available Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively. The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively, indicating that greater accumulation of maleic acid occurred in the rat kidney.

  1. Determination of boron distribution in rat's brain, kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Pazirandeh, Ali [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Science and Technology Research Center, AEOI, Tehran (Iran, Islamic Republic of)], E-mail: paziran@khayam.ut.ac.ir; Jameie, Behnam [Neuroscience Lab, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Zargar, Maysam [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2009-07-15

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  2. The study regarding effect of paraoxon on oxidative stress index in kidney tissue of rats

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    Maryam Abbasnezhad1

    2009-01-01

    Full Text Available (Received 14 July, 2009 ; Accepted 23 December, 2009AbstractBackground and purpose: Paraoxon is the active form of parathion, which is an organophosphate pesticide (OP. The toxic effects of some OPs are not limited to inhibition of cholinesterase, they are capable to produce free radicals and induce disturbance in body antioxidant systems. The purpose of this study was to evaluate the effect of paraoxon on oxidative stress index in the kidney of rat.Materials and methods: Wistar male rats were randomly divided in four groups including: control (corn oil as paraoxon solvent and three paraoxon groups receiving different doses (0.3, 0.7 and 1mg/kg by intraperitoneal injection. 24 hours after injection, animal was given anesthesia and kidney tissue removed. After kidney tissue hemogenation, superoxide dismutase (SOD and catalase (CAT, lactate dehydrogenase (LDH and glutathione S- transferase (GST activities, glutathione (GSH and malondialdehyde (MDA levels were determined by biochemical methods.Results: At doses higher than 0.3 mg/kg paraoxon, kidney SOD and CAT activities were significantly increased, comparing with the control, while GSH level was significantly decreased. There were no significant changes observed in GST, LDH activities and MDA levels.Conclusion: The results suggest that paraoxon induces the production of free radicals and oxidative stress. The enhanced activity of antioxidant enzymes in kidney of rats probably was a function of the increased detoxification capacity. Depletion of tissue GSH is a prime factor, which can impair the cell’s defense against the toxic actions of free radicals.J Mazand Univ Med Sci 2009; 19(73: 17-26 (Persian.

  3. Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats

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    Toedebusch Ryan G

    2012-06-01

    Full Text Available Abstract The purpose of this study was: aim 1 compare insulin and leucine serum responses after feeding a novel hydrolyzed whey protein (WPH-based supplement versus a whey protein isolate (WPI in rats during the post-absorptive state, and aim 2 to perform a thorough toxicological analysis on rats that consume different doses of the novel WPH-based supplement over a 30-day period. In male Wistar rats (~250 g, n = 40, serum insulin and leucine concentrations were quantified up to 120 min after one human equivalent dose of a WPI or the WPH-based supplement. In a second cohort of rats (~250 g, n = 20, we examined serum/blood and liver/kidney histopathological markers after 30 days of feeding low (1human equivalent dose, medium (3 doses and high (6 doses amounts of the WPH-based supplement. In aim 1, higher leucine levels existed at 15 min after WPH vs. WPI ingestion (p = 0.04 followed by higher insulin concentrations at 60 min (p = 0.002. In aim 2, liver and kidney histopathology/toxicology markers were not different 30 days after feeding with low, medium, high dose WPH-based supplementation or water only. There were no between-condition differences in body fat or lean mass or circulating clinical chemistry markers following the 30-day feeding intervention in aim 2. In comparison to WPI, acute ingestion of a novel WPH-based supplement resulted in a higher transient leucine response with a sequential increase in insulin. Furthermore, chronic ingestion of the tested whey protein hydrolysate supplement appears safe.

  4. Eleven reasons to control the protein intake of patients with chronic kidney disease.

    Science.gov (United States)

    Fouque, Denis; Aparicio, Michel

    2007-07-01

    For many years patients with chronic kidney disease have been advised to control the protein content of their diet. This advice has been given on the basis of a number of reported metabolic effects of lowering protein intake, such as lowering serum urea nitrogen levels, improving phosphocalcic metabolism and insulin resistance and, more recently, ameliorating proteinuria (independent of antiproteinuric medications). The effects on the progression of kidney disease, although spectacular in experimental studies, have been less convincing in humans. It is possible that flawed design of clinical trials is responsible for this discrepancy. In this Review, we comment on experimental findings that indicate that limiting protein intake protects the kidney and ameliorates uremic symptoms, outline how the body adapts to a reduction in protein intake, and describe the metabolic benefits to the patient. We then review the evidence from randomized controlled trials and meta-analyses that pertains to the effects of low-protein diets in adults with chronic kidney disease.

  5. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

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    Atefeh Mahmoudi

    2013-11-01

    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

  6. Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

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    Martina eSeifert

    2012-07-01

    Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

  7. Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

    International Nuclear Information System (INIS)

    Cheung, W.K.

    1985-01-01

    The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model was able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C 14 -warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible

  8. Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein-substituted mucuna flour and derived protein rich product.

    Science.gov (United States)

    Ngatchic, Josiane Therese Metsagang; Sokeng, Selestion Dongmo; Njintang, Nicolas Yanou; Maoundombaye, Theophile; Oben, Julius; Mbofung, Carl Moses F

    2013-07-01

    This comparative study reports the nutritional and toxicological characteristics of Mucuna pruriens flour and a protein-rich product developed from it. The protein-rich mucuna product (PRMP) was obtained by the three steps procedure: protein solubilization, heat-coagulation and sieving. Three weeks rats (n=6 per group) were fed for 28 days on standard protein-substituted rat feed with mucuna flour or PRMP. The experimental design was a factorial design with three mucuna accessions (Velvet, Black and White) and two treatments (flour and PRMP). The protein content ranged 27.2-31.5 g/100 g for flour and 58.8-61.1% for PRMP. Processing flour into PRMP led to a significant (pmucuna flour lost weight. The levels of total cholesterol, HDL-cholesterol and LDL-cholesterol observed in animals groups fed mucuna flour and PRMP were significantly lower (pmucuna flour were significantly (pmucuna flour. PRMP then represents a good alternative of using mucuna proteins for human nutrition. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  9. Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.

    Science.gov (United States)

    Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying

    2018-05-01

    Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.

  10. Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Kumar, Gurusiddaiah Suresh; Salimath, Paramahans Veerayya

    2014-01-01

    Curcumin known to have number of medicinal use and masked the fiber containing ukonan like active polysaccharide in turmeric and its pharmacological effect will be addressed on diabetic nephropathy particularly the glycoconjugates of extracellular components viz., glycoproteins and glycosaminoglycans - heparan sulfate (HS). Male Wistar rats were maintained on AIN-76 diet containing 10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC and SFD/TFD, respectively. Diabetic status was monitored using blood and urine, and at the end, harvested kidneys were used to study the amelioration of glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric, hydroxyproline and agarose electrophoretic methods. In the present study spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate (50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney. Increased collagen content in diabetic group was observed by hydroxyproline estimation (24%) and periodic acid-Schiff's (PAS) staining. Furthermore, elevated activities of enzymes involved in the synthesis and degradation of glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed diabetic group. Improvement in total GAGs (43%) and sulfate content (18%) followed by fractionation of GAGs using specific enzymes led to HS (28%) in the spent turmeric fed diabetic group, when compared to starch fed diabetic group and was further confirmed by electrophoresis of GAG. These results clearly indicate beneficial role of spent turmeric in controlling glycoconjugates such as glycoproteins and heparan sulfate related kidney complications during diabetes.

  11. Elemental imaging of kidneys of adult rats exposed to uranium acetate

    Energy Technology Data Exchange (ETDEWEB)

    Homma-Takeda, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: shino_ht@nirs.go.jp; Terada, Y. [Japan Synchrotron Radiation Research Institute, Mikazuki, Hyogo 679-5198 (Japan); Nakata, A.; Sahoo, S.K.; Yoshida, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Ueno, S. [School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628 (Japan); Inoue, M. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Iso, H.; Ishikawa, T.; Konishi, T.; Imaseki, H. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Y. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2009-06-15

    Concern about the toxicity of depleted uranium for military use has increased recently. Renal toxicity is the hallmark effect of uranium exposure. However, the dynamics and distribution of uranium in the kidney are not well understood. Here, we determined the precise distribution of uranium and essential elements in the rat kidney using microbeam scanning particle-induced X-ray emission (micro-PIXE) and synchrotron radiation X-ray fluorescence (SR-XRF). Uranium accumulation in the rat kidney reached a maximum at 1 day after the subcutaneous (s.c.) administration of 2 mg U/kg of uranium acetate and then gradually decreased. At 3 h after administration, uranium was distributed mainly in the proximal tubules of the inner zone of the cortex and in the outer stripe of the outer medulla, and absorbed by the proximal tubule epithelium. Iron was localized more in the inside of the outer medulla than uranium, while phosphorus, potassium, sulfur and zinc were equally distributed in the cortex and the outer stripe of the outer medulla. At 3 days after administration, the number of apoptotic cells increased and cells were lost from the proximal tubules. Uranium was detectable mainly in the outer stripe of the outer medulla at 15 days, suggesting that the renal distribution of uranium is site-selective and causes site-specific renal lesions.

  12. Phosphorylation of rat kidney Na-K pump at Ser938 is required for rapid angiotensin II-dependent stimulation of activity and trafficking in proximal tubule cells.

    Science.gov (United States)

    Massey, Katherine J; Li, Quanwen; Rossi, Noreen F; Keezer, Susan M; Mattingly, Raymond R; Yingst, Douglas R

    2016-02-01

    How angiotensin (ANG) II acutely stimulates the Na-K pump in proximal tubules is only partially understood, limiting insight into how ANG II increases blood pressure. First, we tested whether ANG II increases the number of pumps in plasma membranes of native rat proximal tubules under conditions of rapid activation. We found that exposure to 100 pM ANG II for 2 min, which was previously shown to increase affinity of the Na-K pump for Na and stimulate activity threefold, increased the amount of the Na-K pump in plasma membranes of native tubules by 33%. Second, we tested whether previously observed increases in phosphorylation of the Na-K pump at Ser(938) were part of the stimulatory mechanism. These experiments were carried out in opossum kidney cells, cultured proximal tubules stably coexpressing the ANG type 1 (AT1) receptor, and either wild-type or a S938A mutant of rat kidney Na-K pump under conditions found by others to stimulate activity. We found that 10 min of incubation in 10 pM ANG II stimulated activity of wild-type pumps from 2.3 to 3.5 nmol K · mg protein(-1) · min(-1) and increased the amount of the pump in the plasma membrane by 80% but had no effect on cells expressing the S938A mutant. We conclude that acute stimulation of Na-K pump activity in native rat proximal tubules includes increased trafficking to the plasma membrane and that phosphorylation at Ser(938) is part of the mechanism by which ANG II directly stimulates activity and trafficking of the rat kidney Na-K pump in opossum kidney cells.

  13. Morphological aspects of the rat kidney preserved by cold storage. III. Ultrastructural aspects.

    Science.gov (United States)

    Neagu, S; Gabrielescu, E; Codorean, E; Chirculescu, A R

    1983-01-01

    The ultrastructural changes of the white Wistar rat kidney, preserved by cold storage into two preservation media (Sacks and Plasmagel) are reported. For each medium two groups of kidney were used; for one of them the medium was used without additives and for the other stabilizing additives were added. The results showed the favourable effects of additives on the maintenance of the cellular ultrastructure during preservation, and more important the damages incurred when Plasmagel was used.

  14. Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure.

    Science.gov (United States)

    Mesquita, Flávia Fernandes; Gontijo, José Antonio Rocha; Boer, Patrícia Aline

    2010-02-01

    Intrauterine growth restriction due to low maternal dietary protein during pregnancy is associated with retardation of foetal growth, renal alterations and adult hypertension. The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the control of cardiovascular, renal and adrenal function that governs body fluid and electrolyte balance, as well as arterial pressure. In the kidney, all the components of the renin-angiotensin system including angiotensin II type 1 (AT1) and type 2 (AT2) receptors are expressed locally during nephrogenesis. Hence, we investigated whether low protein diet intake during pregnancy altered kidney and adrenal expression of AT1(R) and AT2(R) receptors, their pathways and if the modified expression of the RAS compounds occurs associated with changes in urinary sodium and in arterial blood pressure in sixteen-week-old males' offspring of the underfed group. The pregnancy dams were divided in two groups: with normal protein diet (pups named NP) (17% protein) or low protein diet (pups LP) (6% protein) during all pregnancy. The present data confirm a significant enhancement in arterial pressure in the LP group. Furthermore, the study showed a significantly decreased expression of RAS pathway protein and Ang II receptors in the kidney and an increased expression in the adrenal of LP rats. The detailed immunohistochemical analysis of RAS signalling proteins in the kidney confirm the immunoblotting results for both groups. The present investigation also showed a pronounced decrease in fractional urinary sodium excretion in maternal protein-restricted offspring, compared with the NP age-matched group. This occurred despite unchanged creatinine clearance. The current data led us to hypothesize that foetal undernutrition could be associated with decreased kidney expression of AT(R) resulting in the inability of renal tubules to handle the hydro-electrolyte balance, consequently causing arterial hypertension.

  15. Tissue injury after lithium treatment in human and rat postnatal kidney involves glycogen synthase kinase 3β-positive epithelium

    DEFF Research Database (Denmark)

    Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2012-01-01

    plasma lithium concentration of 1.0 mmol/L. Kidneys from lithium-treated rat pups exhibited dilated distal nephron segments with microcysts. Stereological analysis showed reduced cortex and outer medullary volumes. Lithium increased pGSK-3β and the proliferation marker PCNA protein abundances in cortex...... concentration capacity and diminished outer medullary volume. Histological sections of nephrectomy samples and a biopsy from 3 long-term lithium-treated patients showed multiple cortical microcysts that originated from normally appearing tubules. Microcysts were lined by a cuboidal PCNA-, GSK-3β- and pGSK-3β......It was hypothesized that lithium causes accelerated and permanent injury to the postnatally developing kidney through entry into epithelial cells of the distal nephron and inhibition of glycogen synthase kinase-3β (GSK-3β). GSK-3β immunoreactivity was associated with glomeruli, thick ascending limb...

  16. 9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

    Science.gov (United States)

    Asciak, C P; Domazet, Z

    1975-02-20

    1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

  17. Effect of dimethylaminoethanol, an inhibitor of betaine production, on the disposition of choline in the rat kidney

    International Nuclear Information System (INIS)

    Lohr, J.; Acara, M.

    1990-01-01

    The choline metabolite betaine has been shown to be an important organic osmoregulatory solute in the kidney. The isolated perfused rat kidney and kidney slice incubations were used to investigate the effect of 2-dimethylaminoethanol (DMAE), a choline oxidase inhibitor, on the renal excretion and metabolism of choline. In the isolated perfused kidney, [ 14 C]choline, at an initial perfusate concentration of 300 microM, was effectively removed from the perfusate over 25 min, with nearly all the 14 C in the perfusate accounted for by betaine during the remainder of the 90-min perfusion. DMAE at concentrations of 3.0 or 5.0 mM significantly decreased the rate of removal of [ 14 C]choline from the perfusate and the rate of addition of [ 14 C]betaine to the perfusate, yet [14C]betaine remained the only metabolite of choline in perfusate and urine. In kidney tissue slice experiments, conversion of [ 14 C]choline to [ 14 C]betaine was found in cortical, outer medullary and inner medullary regions of rat kidney. DMAE at 5.0 mM significantly inhibited [ 14 C]betaine production in each of the three regions studied. These data show that DMAE is an effective inhibitor of betaine production by the kidney and, as such, may be an important agent for the study of osmoregulation by the kidney

  18. Ultrastructural changes in the isolated rat kidney induced by conjugated bilirubin and bile acids.

    Science.gov (United States)

    Gollan, J L; Billing, B H; Huang, S N

    1976-10-01

    The effects of bilirubin and bile acids on the ultrastructure of proximal renal tubules have been studied using an isolated rat kidney preparation, perfused with a protein-free dextran medium. Control kidneys perfused for 1 h had a normal glomerular filtration rate and effective renal plasma flow; the ultrastructure of proximal tubular cells was well preserved, with normal mitochondria, nuclear and plasma membranes, and microvilli of the brush border. When conjugated bilirubin, prepared from human hepatic bile, was added to the perfusion medium (5-0-7-5 mg/100 ml), marked alterations were observed in some cells, particularly with regard to the mitochondria and plasma membranes. These changes were greatly diminished by the inclusion of bovine albumin in the medium, indicating that the unbound fraction was primarily responsible for the tubular damage. The addition of taurocholate (450 muM), taurochenodeoxycholate (550 muM) or taurolithocholate (250 muM, bound to albumin) also produced plasma membrane changes, but only slight abnormalities were seen in the mitochondria and other structures. These ultrastructural observations support the concept that the elevated plasma levels of conjugated bilirubin and to a lesser extent bile acids are related to the renal failure associated with obstructive jaundice.

  19. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat

    Directory of Open Access Journals (Sweden)

    Sumaira Sahreen

    2015-09-01

    Full Text Available Background: Carbon tetrachloride (CCl4 is a potent nephrotoxin, as it causes acute as well as chronic toxicity in kidneys. Therefore, this study was carried out to assess the pharmacological potential of different fractions of Carissa opaca fruits on CCl4-induced oxidative trauma in the kidney. Methods: The parameters studied in this respect were the kidney function tests viz, serum profile, urine profile, genotoxicity, characteristic morphological findings, and antioxidant enzymatic level of kidneys. Result: The protective effects of various fractions of C. opaca fruits against CCl4 administration were reviewed by rat renal function alterations. Chronic toxicity caused by 8-week treatment of CCl4 to the rats significantly decreased the pH level, activities of antioxidant enzymes, and glutathione contents, whereas a significant increase was found in the case of specific gravity, red blood cells, white blood cells, level of urea, and lipid peroxidation in comparison to control group. Administration of various fractions of C. opaca fruit with CCl4 showed protective ability against CCl4 intoxication by restoring the urine profile, activities of antioxidant enzymes, and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and glomerular atrophy by means of dilation, disappearance of Bowmen's space, congestion in the capillary loops, dilation in renal tubules, and foamy look of epithelial cells of tubular region, which were restored by co-admiration of various fractions of C. opaca. Conclusion: Results revealed that the methanolic fractions of C. opaca are the most potent and helpful in kidney trauma.

  1. First-trimester maternal protein intake and childhood kidney outcomes: the Generation R Study.

    Science.gov (United States)

    Miliku, Kozeta; Voortman, Trudy; van den Hooven, Edith H; Hofman, Albert; Franco, Oscar H; Jaddoe, Vincent W V

    2015-07-01

    Nutritional exposures during in utero development may have long-lasting consequences for postnatal renal health. Animal studies suggest that specifically maternal dietary protein intake during pregnancy influences childhood kidney function. We examined the associations of total, animal, and vegetable maternal protein intake during pregnancy with kidney volume and function in school-aged children. This study was conducted in 3650 pregnant women and their children who were participating in a population-based cohort study from early life onward. First-trimester energy-adjusted maternal protein intake was assessed with a food-frequency questionnaire. At the child's age of 6 y, we assessed kidney volume, estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C concentrations, and microalbuminuria using urine albumin:creatinine ratios. First-trimester maternal total protein intake was associated with a higher childhood creatinine-based eGFR (difference: 0.06 mL × min(-1) × 1.73 m(-2); 95% CI: 0.01, 0.12 mL · min(-1) · 1.73 m(-2) per gram of protein intake). This association was mainly driven by vegetable protein intake (0.22 mL × min(-1) × 1.73 m(-2); 95% CI: 0.10, 0.35 mL · min(-1) · 1.73 m(-2) per gram of vegetable protein intake). These associations were not explained by protein intake in early childhood. First-trimester maternal protein intake was not significantly associated with childhood kidney volume, cystatin C-based eGFR, or the risk of microalbuminuria. Our findings suggest that higher total and vegetable, but not animal, maternal protein intake during the first trimester of pregnancy is associated with a higher eGFR in childhood. Further follow-up studies are needed to investigate whether maternal protein intake in early pregnancy also affects the risk of kidney diseases in later life. © 2015 American Society for Nutrition.

  2. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

    Science.gov (United States)

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

  3. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Science.gov (United States)

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  4. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheila Marques Fernandes

    2016-01-01

    Full Text Available Iodinated contrast (IC is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI. Chronic kidney disease (CKD and chronic hyperglycemia (CH are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH; Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  5. Protein-Energy Wasting and Mortality in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ezio Gianetta

    2011-05-01

    Full Text Available Protein-energy wasting (PEW is common in patients with chronic kidney disease (CKD and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome.

  6. Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys.

    Science.gov (United States)

    Wang, Kun; Wu, Yong-Gui; Su, Jing; Zhang, Jing-Jing; Zhang, Pei; Qi, Xiang-Ming

    2012-01-01

    Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall., which has shown renoprotection in experimental diabetic nephropathy. Activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage. Macrophages also play an essential role in the pathogenesis of diabetic nephropathy. Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. TGP (50, 100, and 200 mg/kg) was administered orally once a day for eight weeks. Levels of p-JAK2 and p-STAT3 were determined by Western blot analysis. Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. The elevated 24-h urinary albumin excretion rate was markedly attenuated by treatment with 50, 100, and 200 mg/kg TGP. Western blot analysis showed that the significantly increased levels of p-JAK2, p-STAT3 proteins in the kidneys of diabetic rats were significantly inhibited by 50, 100, and 200 mg/kg TGP treatment. The marked accumulation and proliferation of macrophages in diabetic kidneys were significantly inhibited by TGP treatment. ED-1+/p-STAT3+ cells were significantly increased in the kidneys from the model group but were significantly inhibited by TGP treatment. These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action.

  7. The kidneys play a central role in the clearance of rhGH in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads

    2016-01-01

    at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...... that renal clearance plays a pivotal role in the elimination of rhGH in rats....

  8. Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Kim, Yun-Bae; Kim, Jong-Choon

    2017-11-01

    This study investigated the dose-response effects of pine bark extract (PBE, pycnogenol ® ) on oxidative stress-mediated apoptotic changes induced by cisplatin (Csp) in rats. The ameliorating potential of PBE was evaluated after orally administering PBE at doses of 10 or 20 mg/kg for 10 days. Acute kidney injury was induced by a single intraperitoneal injection of Csp at 7 mg/kg on test day 5. Csp treatment caused acute kidney injury manifested by elevated levels of serum blood urea nitrogen (BUN) and creatinine (CRE) with corresponding histopathological changes, including degeneration of tubular epithelial cells, hyaline casts in the tubular lumen, and inflammatory cell infiltration (interstitial nephritis). Csp also induced significant apoptotic changes in renal tubular cells. In addition, Csp treatment induced high levels of oxidative stress, as evidenced by an increased level of malondialdehyde, depletion of the reduced glutathione (GSH) content, and decreased activities of glutathione S-transferase, superoxide dismutase, and catalase in kidney tissues. On the contrary, PBE treatment lowered BUN and CRE levels and effectively attenuated histopathological alterations and apoptotic changes induced by Csp. Additionally, treatment with PBE suppressed lipid peroxidation, prevented depletion of GSH, and enhanced activities of the antioxidant enzymes in kidney tissue. These results indicate that PBE has a cytoprotective effect against oxidative stress-mediated apoptotic changes caused by Csp in the rat kidney, which may be attributed to both increase of antioxidant enzyme activities and inhibition of lipid peroxidation.

  9. Effect of diet protein quality on growth and protein synthesis in rats

    International Nuclear Information System (INIS)

    Chinchalkar, D.V.; Mehta, S.L.

    1978-01-01

    The effect of diet protein quality on albino rats was studied by feeding normal and opaque-2 maize. The weight gain in rats was 60 percent higher on opaque-2 maize as compared to those fed on normal maize. Rats converted 1.0 g of dietary opaque-2 maize to 0.226 g weight gain as compared to 0.131 g for normal maize. The protein content per liver was higher with opaque-2 maize diet suggesting a higher net protein synthesis in opaque-2 maize fed rat livers. In vitro 14 C-phenylalanine incorporation showed that polysomes from opaque-2 maize fed rat livers were more efficient in protein synthesis than those from normal maize fed rat livers. Addition of poly-U resulted in more enhanced amino acid incorporation with polysomes from normal maize fed rats as compared to other group indicating greater limitation of mRNA in polysomes from normal maize fed rats. The total yield of liver polysomes from opaque-2 maize fed rats was substantially higher. (author)

  10. Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

    Science.gov (United States)

    Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

    2016-11-01

    Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

    Science.gov (United States)

    Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

    2016-01-01

    Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

  12. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

    Directory of Open Access Journals (Sweden)

    José Sereno

    2014-01-01

    Full Text Available Protocols of conversion from cyclosporin A (CsA to sirolimus (SRL have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n=6 were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks. Classical and emergent serum, urinary, and kidney tissue (gene and protein expression markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions, while NGAL (serum versus urine seems to be a feasible biomarker of CsA replacement to SRL.

  13. Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

    Science.gov (United States)

    Burukoglu, Dilek; Baycu, Cengiz; Taplamacioglu, Fulya; Sahin, Erhan; Bektur, Ezgi

    2016-06-01

    Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration. © The Author(s) 2014.

  14. Possible participation of oxidative stress in causation of cell proliferation and in vivo mutagenicity in kidneys of gpt delta rats treated with potassium bromate

    International Nuclear Information System (INIS)

    Umemura, Takashi; Tasaki, Masako; Kijima, Aki; Okamura, Toshiya; Inoue, Tomoki; Ishii, Yuji; Suzuki, Yuta; Masui, Norio; Nohmi, Takehiko; Nishikawa, Akiyoshi

    2009-01-01

    Clarifying the participation of oxidative stress among possible contributing factors in potassium bromate (KBrO 3 )-induced carcinogenesis is of importance from the perspective of human health protection. In the present study, utilizing the antioxidative effects of α-tocopherol (α-TP) or sodium ascorbic acid (SAA) to attenuate oxidative stress, alterations in bromodeoxyuridine labeling indices (BrdU-LIs) and reporter gene mutations in kidneys of male and female gpt delta rats given KBrO 3 were examined. Five male and female gpt delta rats in each group were given KBrO 3 at a concentration of 500 ppm in the drinking water for 9 weeks, with 1% of α-TP or SAA administered in the diet from 1 week prior to the KBrO 3 treatment until the end of the experiment. Increases in 8-hydroxydeoxyguanosine levels in kidney DNA of both sexes of rats given KBrO 3 were significantly inhibited by SAA, but not α-TP. While BrdU-LIs in the proximal tubules of female rats were also significantly reduced by SAA, those in the males and gpt mutant frequencies in kidney DNA of both sexes were not affected by SAA or α-TP. Immunohistochemical and Western blot analyses for α 2u -globulin strongly suggested that induction of cell proliferation observed in the males might primarily result from accumulation of this protein, independent of oxidative stress. The overall data indicated that while oxidative stress well correlates with induction of cell proliferation in females, its role in males and in generation of in vivo mutagenicity by KBrO 3 in both sexes is limited

  15. Determination of reference values of elements in kidney of the wistar rats using NAA

    International Nuclear Information System (INIS)

    Oliveira, Laura C.; Zamboni, Cibele B.

    2013-01-01

    The aim of the present study is to establish Reference Value for elements in kidney of Wistar rats using the Neutron Activation Analysis technique. The quantitative knowledge of these elements in this biological material allows researchers to optimize their studies, both in terms of cost and time, selecting the species that fits to the experimental model as a clinical reference, as well as the realization of biochemical investigation in kidney. In this study, the reference values (mg/kg) for kidney were determined for: Cr (0.0276 - 0.0384), Fe (110.23 - 212.87), Rb (2.8 - 6.8) and Zn (78.40 - 84.56). (author)

  16. Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Stubbe, Jane; Skøtt, Ole

    2004-01-01

    COX-2 in these cells. Thus low plasma concentrations of corticosterone allowed for cortical and medullary COX-2 induction during postnatal kidney development. Increased circulating glucocorticoid in the postnatal period may damage late renal development through inhibition of COX-2.......In postnatal weeks 2-4, cyclooxygenase-2 (COX-2) is induced in the rat kidney cortex where it is critically involved in final stages of kidney development. We examined whether changes in circulating gluco- or mineralocorticosteroids or in their renal receptors regulate postnatal COX-2 induction....... Plasma corticosterone concentration peaked at birth, decreased to low levels at days 3-13, and increased to adult levels from day 22. Aldosterone peaked at birth and then stabilized at adult levels. Gluco- and mineralocorticoid receptor (GR and MR) mRNAs were expressed stably in kidney before, during...

  17. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  18. Nuclear factor κB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney.

    Science.gov (United States)

    Kowalczyk, Agata; Kołodziejczyk, Michał; Gorąca, Anna

    2015-12-31

    The aim of the study was to evaluate the effect of BAY 11-7082, an NF-κB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-α and p65 protein in rat kidney. The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 μg/kg body weight (b.w.) or 12.5 μg/kg b.w.; 4) BAY 11-7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 μg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-α, p65 protein and GSH/GSSG ratio were determined. ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 μg/kg resulted in a decrease (PET-1 groups. The level of TNF-α was increased (PET-1, while BAY 11-7082 reduced the TNF-α level (PET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-κB signaling pathways. Inhibition of the NF-κB pathway may be a promising strategy for preventing the progression of kidney damage.

  19. [A study on the relationship between postmortem interval and the changes of DNA content in the kidney cellule of rat].

    Science.gov (United States)

    Liu, L; Peng, D B; Liu, Y; Deng, W N; Liu, Y L; Li, J J

    2001-05-01

    To study changes of DNA content in the kidney cellule of rats and relationship with the postmortem interval. This experiment chose seven parameter of cell nuclear, including the area and integral optical density, determined the changes of DNA content in the kidney cellule of 15 rats at different intervals between 0 and 48 h postmortem with auto-TV-image system. The degradation rate of DNA in nuclear has a certainty relationship to early PMI(in 48 h) of rat, and get binomial regress equation. Determining the quantity of DNA in nuclear should be an objective and exact way to estimate the PMI.

  20. Effect of alpha-calciferol on bone mineral density, bone histomorphometry and bone biomechanics in rats by radiative injury to kidney

    International Nuclear Information System (INIS)

    Zhu Feipeng; Wang Hongfu; Gao Linfeng; Jin Weifang

    2003-01-01

    The work is to study the effects of alpha-calciferol on bone mineral density, histomorphometry and biomechanics in rats with osteoporosis induced by irradiation of the rat kidney. 32 male SD rats of six months in age were randomly divided into 4 groups (8 rats per group), i.e. the model group, the sham group, the bone one group and the fosamax group. Osteoporosis was developed in the rats by irradiating the kidney. Then the rats were administrated orally as follows in a 90 days, 0.1 g·kg -1 BW.d of alpha-calciferol for the bone one group, 10 mg·kg -1 BW.d of alendronate sodium in 1 mL CMC for the fosamax group, and 1 mL CMC for both the model group and sham group. BMD of L1-4, bone histomorphometry and the bone biomechanical properties were measured. Compared with the model group, both the bone one group and the fosamax group were characterized with significantly higher BMD of L1-4 (p<0.01), significantly larger volume and width of bone trabecula, smaller space of bone trabecula (p<0.05, p<0.01), and significantly larger maximal stress of femur and lumbar vertebra (p<0.05, p<0.01). It is concluded that Alpha-calciferol can improve BMD, bone histomorphometry and bone biomechanical properties in rat osteoporosis induced by kidney irradiation

  1. In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues

    International Nuclear Information System (INIS)

    Thompson, W.L.; Wannemacher, R.W. Jr.

    1990-01-01

    Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies

  2. Water and exchangeable sodium in Goldblatt two-kidney, two-clip hypertensive rats

    International Nuclear Information System (INIS)

    Mac Cormack, W.P.; Roson, M.I.; Maquieira, M.K.; Mendez, M.A.; Santoro, F.M.; Morera, S.; de la Riva, I.J.

    1986-01-01

    Exchangeable 22 Na (ExNa), total body water (TBW) and the inulin space (InSp) were determined in two-kidney, two-clip (2K-2C) hypertensive and sham operated (normotensive) control rats 6-8 weeks after surgery. TBW (ml/kg lean body weight) was the same in hypertensive and sham rats. In contrast, ExNa (mEq/kglbw) and InSp (ml/kglbw) significantly increased (p less than 0.01) in rats whose hypertension did not exceed 170 mmHg. Consequently, sham, moderate hypertensive (less than 170 mmHg) and severe hypertensive (less than 170 mmHg) animals showed equal TBW but differed in body water distribution in that moderately hypertensive animals displayed a redistribution of water in favor of the extracellular space

  3. Comparative toxicology of carfene in male and female rats

    International Nuclear Information System (INIS)

    Hassanin, M.M.; Tawfik, S.M.F.

    2005-01-01

    The objective of this study was to determine the potential toxicity associated with daily oral administrations of carfene (2.5 mg/kg body weight) for 15 consecutive days on protein level in liver, kidney, brain and spleen tissues of male and female rats after 1, 5, 10 and 15 days of treatment. Evaluation of the trace elements, zinc and copper in serum, revealed that zinc level was decreased significantly while that of copper was increased in both male and female rats compared to controls. The incorporation rate of 14 C-isoleucine for synthesis of protein tended to decrease in liver tissues and increase in brain tissues of rats. Kidney and spleen tissues showed fluctuated changes. It was noticed in the present investigation that the incorporation rate of I4 C-radioactivity in different selected tissues under estimation was more pronounced in male than in female rats

  4. Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney.

    Science.gov (United States)

    Mariappan, Meenalakshmi M; DeSilva, Kristin; Sorice, Gian Pio; Muscogiuri, Giovanna; Jimenez, Fabio; Ahuja, Seema; Barnes, Jefferey L; Choudhury, Goutam Ghosh; Musi, Nicolas; DeFronzo, Ralph; Kasinath, Balakuntalam S

    2014-02-01

    Increase in matrix protein content in the kidney is a cardinal feature of diabetic kidney disease. While renal matrix protein content is increased by chronic hyperglycemia, whether it is regulated by acute elevation of glucose and insulin has not been addressed. In this study, we aimed to evaluate whether short duration of combined hyperglycemia and hyperinsulinemia, mimicking the metabolic environment of prediabetes and early type 2 diabetes, induces kidney injury. Normal rats were subjected to either saline infusion (control, n = 4) or 7 h of combined hyperglycemic-hyperinsulinemic clamp (HG+HI clamp; n = 6). During the clamp, plasma glucose and plasma insulin were maintained at about 350 mg/dl and 16 ng/ml, respectively. HG+HI clamp increased the expression of renal cortical transforming growth factor-β (TGF-β) and renal matrix proteins, laminin and fibronectin. This was associated with the activation of SMAD3, Akt, mammalian target of rapamycin (mTOR) complexes, and ERK signaling pathways and their downstream target events in the initiation and elongation phases of mRNA translation, an important step in protein synthesis. Additionally, HG+HI clamp provoked renal inflammation as shown by the activation of Toll-like receptor 4 (TLR4) and infiltration of CD68-positive monocytes. Urinary F2t isoprostane excretion, an index of renal oxidant stress, was increased in the HG+HI clamp rats. We conclude that even a short duration of hyperglycemia and hyperinsulinemia contributes to activation of pathways that regulate matrix protein synthesis, inflammation, and oxidative stress in the kidney. This finding could have implications for the control of short-term rises in blood glucose in diabetic individuals at risk of developing kidney disease.

  5. The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity

    International Nuclear Information System (INIS)

    Stiborova, Marie; Dracinska, Helena; Mizerovska, Jana; Frei, Eva; Schmeiser, Heinz H.; Hudecek, Jiri; Hodek, Petr; Phillips, David H.; Arlt, Volker M.

    2008-01-01

    3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air pollution. Using the 32 P-postlabelling method, we found that 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical five DNA adducts. We have demonstrated the importance of pulmonary and renal NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP) 1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When cytosols from rats treated i.p. with 40 mg/kg bw of 3-NBA were incubated with 3-NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. Incubations of 3-ABA with microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct formation relative to controls. The stimulation of DNA adduct formation correlated with the potential of 3-NBA to induce protein expression and activity of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential

  6. Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Sato, Masao [Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical College, Fukushima (Japan); Konno, Nobuhiro [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Fukushima, Masaaki [Department of Public Health, Fukushima Medical College, Fukushima (Japan)

    1996-11-01

    Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. (orig.). With 4 figs., 4 tabs.

  7. An attempt to understand kidney's protein handling function by comparing plasma and urine proteomes.

    Directory of Open Access Journals (Sweden)

    Lulu Jia

    Full Text Available BACKGROUND: With the help of proteomics technology, the human plasma and urine proteomes, which closely represent the protein compositions of the input and output of the kidney, respectively, have been profiled in much greater detail by different research teams. Many datasets have been accumulated to form "reference profiles" of the plasma and urine proteomes. Comparing these two proteomes may help us understand the protein handling aspect of kidney function in a way, however, which has been unavailable until the recent advances in proteomics technology. METHODOLOGY/PRINCIPAL FINDINGS: After removing secreted proteins downstream of the kidney, 2611 proteins in plasma and 1522 in urine were identified with high confidence and compared based on available proteomic data to generate three subproteomes, the plasma-only subproteome, the plasma-and-urine subproteome, and the urine-only subproteome, and they correspond to three groups of proteins that are handled in three different ways by the kidney. The available experimental molecular weights of the proteins in the three subproteomes were collected and analyzed. Since the functions of the overrepresented proteins in the plasma-and-urine subproteome are probably the major functions that can be routinely regulated by excretion from the kidney in physiological conditions, Gene Ontology term enrichment in the plasma-and-urine subproteome versus the whole plasma proteome was analyzed. Protease activity, calcium and growth factor binding proteins, and coagulation and immune response-related proteins were found to be enriched. CONCLUSION/SIGNIFICANCE: The comparison method described in this paper provides an illustration of a new approach for studying organ functions with a proteomics methodology. Because of its distinctive input (plasma and output (urine, it is reasonable to predict that the kidney will be the first organ whose functions are further elucidated by proteomic methods in the near future. It

  8. Selective affinity labeling of a 27-kDa integral membrane protein in rat liver and kidney with N-bromoacetyl derivatives of L-thyroxine and 3,5,3'-triiodo-L-thyronine

    International Nuclear Information System (INIS)

    Koehrle, J.R.; Rasmussen, U.B.; Rokos, H.; Leonard, J.L.; Hesch, R.D.

    1990-01-01

    125I-Labeled N-bromoacetyl derivatives of L-thyroxine and L-triiodothyronine were used as alkylating affinity labels to identify rat liver and kidney microsomal membrane proteins which specifically bind thyroid hormones. Affinity label incorporation was analyzed by ethanol precipitation and individual affinity labeled proteins were identified by autoradiography after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Six to eight membrane proteins ranging in size from 17 to 84 kDa were affinity labeled by both bromoacetyl-L-thyroxine (BrAcT4) and bromoacetyl-L-triiodothyronine (BrAcT3). Affinity labeling was time- and temperature-dependent, and both reduced dithiols and detergents increased affinity labeling, predominantly in a 27-kDa protein(s). Up to 80% of the affinity label was associated with a 27-kDa protein (p27) under optimal conditions. Affinity labeling of p27 by 0.4 nM BrAc[125I]L-T4 was blocked by 0.1 microM of the alkylating ligands BrAcT4, BrAcT3, or 100 microM iodoacetate, by 10 microM concentrations of the non-alkylating, reversible ligands N-acetyl-L-thyroxine, 3,3',5'-triiodothyronine, 3,5-diiodosalicylate, and EMD 21388, a T4-antagonistic flavonoid. Neither 10 microM L-T4, nor 10 microM N-acetyltriiodothyronine or 10 microM L-triiodothyronine blocked affinity labeling of p27 or other affinity labeled bands. Affinity labeling of a 17-kDa band was partially inhibited by excess of the alkylating ligands BrAcT4, BrAcT3, and iodoacetate, but labeling of other minor bands was not blocked by excess of the competitors. BrAc[125I]T4 yielded higher affinity label incorporation than BrAc[125I]T3, although similar banding patterns were observed, except that BrAcT3 affinity labeled more intensely a 58,000-Da band in liver and a 53,000-55,000-Da band in kidney

  9. Effect of vitamin D status on chick kidney proteins: detection of a 45-kilodalton mitochondrial protein suppressed by vitamin D

    International Nuclear Information System (INIS)

    Kain, S.R.; Kamrath, K.S.; Henry, H.L.

    1988-01-01

    Two-dimensional polyacrylamide gel electrophoresis along with L-[ 35 S]methionine radiolabeling studies were used to examine the effect of chronic vitamin D status on the composition and relative abundance of chick kidney proteins. Comparison of silver-stained gels revealed no extensive differences in either the electrophoretic mobility or the amounts of kidney proteins present in the mitochondrial fraction from vitamin D-replete and vitamin D-deficient chicks. A similar result was obtained in studies with L-[ 35 S]methionine-labeled proteins. Vitamin D deficiency specifically elevated levels of a 45-kilodalton mitochondrial protein (pI 5.0 to 5.5) by approximately 5- to 12-fold relative to amounts present in vitamin D-replete tissue. This protein could not be detected in postmitochondrial supernatant fractions and was only faintly visible in crude kidney homogenates. The specificity of the observed suppression of this 45-kilodalton protein by vitamin D suggests that it may play an important role in renal functions influenced by the vitamin D endocrine system

  10. Utilization of alpha-ketoisocaproate for protein synthesis in uremic rats

    International Nuclear Information System (INIS)

    Tungsanga, K.; Kang, C.W.; Walser, M.

    1986-01-01

    We have recently shown that the nutritional efficiency, R, of alpha-ketoisocaproate (KIC) as a substitute for leucine, defined as the ratio of the dose of leucine to the dose of KIC (on a leucine-free diet) for equal growth, can be evaluated isotopically: 14 C-KIC and 3 H-leucine are administered p.o.; six hours later, 14 C/ 3 H in the leucine of whole body protein, divided by 14 C/ 3 H in the injectate, gives a value distinguishable from R assessed in the same animals by growth experiments. To see how chronic uremia affects R, 11/12 nephrectomized rats and sham-operated controls were fed a regular diet for 15 days and then given these isotopes p.o. Six hours later, R, measured in whole body protein, and in the protein of brain, heart, muscle, salivary gland, liver, and the kidney remnant was significantly greater than in sham-operated controls. The greatest difference (39%) was seen in liver protein and the smallest difference (19%) in muscle. Thus, chronic uremia increases the efficiency, relative to leucine, with which KIC is utilized for protein synthesis in all of these organs and in the body as a whole. Possible explanations are discussed

  11. Utilization of alpha-ketoisocaproate for protein synthesis in uremic rats

    Energy Technology Data Exchange (ETDEWEB)

    Tungsanga, K.; Kang, C.W.; Walser, M.

    1986-12-01

    We have recently shown that the nutritional efficiency, R, of alpha-ketoisocaproate (KIC) as a substitute for leucine, defined as the ratio of the dose of leucine to the dose of KIC (on a leucine-free diet) for equal growth, can be evaluated isotopically: /sup 14/C-KIC and /sup 3/H-leucine are administered p.o.; six hours later, /sup 14/C//sup 3/H in the leucine of whole body protein, divided by /sup 14/C//sup 3/H in the injectate, gives a value distinguishable from R assessed in the same animals by growth experiments. To see how chronic uremia affects R, 11/12 nephrectomized rats and sham-operated controls were fed a regular diet for 15 days and then given these isotopes p.o. Six hours later, R, measured in whole body protein, and in the protein of brain, heart, muscle, salivary gland, liver, and the kidney remnant was significantly greater than in sham-operated controls. The greatest difference (39%) was seen in liver protein and the smallest difference (19%) in muscle. Thus, chronic uremia increases the efficiency, relative to leucine, with which KIC is utilized for protein synthesis in all of these organs and in the body as a whole. Possible explanations are discussed.

  12. Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

    Science.gov (United States)

    Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

    2016-10-01

    Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

    Science.gov (United States)

    Tastekin, Ebru; Palabiyik, Orkide; Ulucam, Enis; Uzgur, Selda; Karaca, Aziz; Vardar, Selma Arzu; Yilmaz, Ali; Aydogdu, Nurettin

    2016-08-01

    Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies.

  14. Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

    Science.gov (United States)

    Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

    2017-05-01

    Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

  15. Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially.

    Science.gov (United States)

    Hsieh, Chiu-Lan; Peng, Chiung-Chi; Chen, Kuan-Chou; Peng, Robert Y

    2013-07-31

    Nutraceutically, much of the literature has indicated that an aglycon and its related glycoside would act similarly. However, controversial reports are accumulating. We hypothesize that rutin (RT) and quercetin (QT) pharmacodynamically could act differently. To confirm this, doxorubicin (DR) (8.5 mg/kg) was used to induce rat chronic kidney disease (CKD) and then treated with QT and RT (each 70 mg/kg body weight per day) for 13 weeks. QT exhibited better body weight gaining effect (420 ± 45) vs RT, 350 ± 57 g/rat (p protein-energy malnutrition". RT stimulated serum creatinine (sCr) production to reach 6.0 ± 0.9 mg/dL (p < 0.001). QT did not alter the sCr level. RT but not QT induced uremia and hypercreatininemia. DR significantly downregulated Bcl-2, but highly upregulated Bax, Bad, and cleaved caspase-3, implicating the intrinsic mitochondrial pathway. DR damaged DNA, but QT completely rescued such an effect and recovered renal amyloidosis and collagen deposition. Conclusively, RT and QT act differently, and RT is inferior to QT with respect to treating CKD.

  16. The Role of Y-Box Binding Protein 1 in Kidney Injury: Friend or Foe?

    Science.gov (United States)

    Ke, Ben; Fan, Chuqiao; Tu, Weiping; Fang, Xiangdong

    2018-01-01

    Y-box-binding protein 1 (YB-1) is a multifunctional protein involved in various cellular processes via the transcriptional and translational regulation of target gene expression. YB-1 promotes acute or chronic kidney injury through multiple molecular pathways; however, accumulating evidence suggests that significantly increased YB-1 levels are of great importance in renoprotection. In addition, YB-1 may contribute to obesity-related kidney disease by promoting adipogenesis. Thus, the role of YB-1 in kidney injury is complicated, and no comprehensive review is currently available. In this review, we summarise recent progress in our understanding of the function of YB-1 in kidney injury and provide an overview of the dual role of YB-1 in kidney disease. Moreover, we propose that YB-1 is a potential therapeutic target to restrict kidney disease. © 2018 The Author(s). Published by S. Karger AG, Basel.

  17. Peroxiredoxin 5 Protects TGF-β Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells.

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    Hoon-In Choi

    Full Text Available Renal fibrosis is a common final pathway of end-stage kidney disease which is induced by aberrant accumulation of myofibroblasts. This process is triggered by reactive oxygen species (ROS and proinflammatory cytokines generated by various source of injured kidney cells. Peroxiredoxin 5 (Prdx5 is a thiol-dependent peroxidase that reduces oxidative stress by catalyzing intramolecular disulfide bonds. Along with its antioxidant effects, expression level of Prdx5 also was involved in inflammatory regulation by immune stimuli. However, the physiological effects and the underlying mechanisms of Prdx5 in renal fibrosis have not been fully characterized. Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO for 1 or 7 days. For the in vitro model, NRK49F cells, a rat kidney interstitial fibroblast cell lines, were treated with transforming growth factor β (TGF-β for 0, 1, 3, or 5 days. To access the involvement of its peroxidase activity in TGF-β induced renal fibrosis, wild type Prdx5 (WT and double mutant Prdx5 (DM, converted two active site cysteines at Cys 48 and Cys 152 residue to serine, were transiently expressed in NRK49F cells. The protein expression of Prdx5 was reduced in UUO kidneys. Upregulation of fibrotic markers, such as fibronectin and alpha-smooth muscle actin (α-SMA, declined at 5 days in time point of higher Prdx5 expression in TGF-β treated NRK49F cells. The overexpression of wild type Prdx5 by transient transfection in NRK49F cells attenuated the TGF-β induced upregulation of fibronectin and α-SMA. On the other hand, the transient transfection of double mutant Prdx5 did not prevent the activation of fibrotic markers. Overexpression of Prdx5 also suppressed the TGF-β induced upregulation of Stat3 phosphorylation, while phosphorylation of Smad 2/3 was unchanged. In conclusion, Prdx5 protects TGF-β induced fibrosis in NRK49F cells by modulating Stat3 activation in a peroxidase activity dependent manner.

  18. Effect of Aerial Parts Extract of Echinophora Platyloba.L on Liver and Kidney Function Tests in Obese Hypercholesterolaemia Rats

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    H Aqababa

    2016-01-01

    Full Text Available Introduction: Obesity and its complications such as hypertension, fatty liver, type 2 diabetes and kidney failure, can be mentioned as the main life-threating elements. Therefore, this study aimed to evaluate the effect of air parts extract of Echinophora platyloba.L (EP on changes in body weight as well as liver and kidney function tests in hypercholesterolaemia obese rats. Methods: In this experimental study, 40 male Wistar rats were divided in to five groups (n =8 including a control group with normal control diet, control hyperlipidemia group with fatty food diet and hypertriglyceridemia treatment groups which recieved the minimum dose (100 mg/kg, average dose (200 mg/kg maximum dose (300 mg/kg of EP extract via a gavage. At the end of this period (42 days, to measure cholesterol, creatinine, blood urea nitrogen, bilirubin, albumin, total protein, alanine Aminotransferase (ALT and aspartate Aminotransferase (AST and alkaline phosphatase (ALP, the blood samples were collected and the study data were analyzed. Results: Cholesterol, ALT, AST and ALP were reported to significantly decrease (in the minimum and maximum dose groups compared to the control group (P≤0.05. Albumin and total protein in the maximum dose extract group significantly increased compared to the control group (P≤0.05. Moreover, body weight in the group receiving the minimum dose of extract showed a significant decrease compared to the control group (P≤0.05. Conclusion: EP extract, specifically in the minimal doses, in addition to protecting liver, could be recommended as a good candidate in regard with the treatment of blood lipids, and body extra weight.

  19. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

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    Nisreen A. Rajeh

    2017-02-01

    Full Text Available exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA and Vitamin E (vit-Eon Acrylamide (ACR induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone. After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E

  20. Effects of dietary level of tannic acid and protein on internal organ weights and biochemical blood parameters of rats.

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    Marcin Barszcz

    Full Text Available Tannic acid (TA is a polyphenolic compound with a health-promoting potential for humans. It is hypothesised that TA effects on the relative weight of internal organs and biochemical blood indices are modified by dietary protein level in rats. The study involved 72 rats divided into 12 groups fed diets with 10 or 18% of crude protein (CP and supplemented with 0, 0.25, 0.5, 1, 1.5 or 2% of TA. After 3 weeks of feeding, the relative weight of the caecum was greater in rats fed TA diets, while feeding diets with 10% of CP increased the relative weight of the stomach, small intestine and caecum, but decreased that of kidneys and spleen. Albumin concentration was higher in rats fed 0.25% and 0.5% TA diets than in rats given the 2% TA diets. The 2% TA diets reduced creatine kinase (CK activity compared to non-supplemented diets and those with 0.5, 1 and 1.5% of TA. Rats fed the 10% CP diets had a higher activity of alkaline phosphatase, amylase, and γ-glutamyltransferase as well as the concentration of iron and cholesterol, but lower that of urea and uric acid. The interaction affected only cholinesterase activity. In conclusion, TA induced caecal hypertrophy and could act as a cardioprotective agent, as demonstrated by reduced CK activity, but these effects were not modified by dietary protein level.

  1. Determination of trace elements in kidneys, livers and brains of rats with sealer implants by ICP-MS

    International Nuclear Information System (INIS)

    Simsek, Neslihan; Akinci, Levent; Alan, Hilal; Gecör, Orhan; Özan, Ülkü

    2017-01-01

    Following root canal treatment, sealers may contact periapical tissue. The purpose of this study was to evaluate the systemic toxic effects of epoxy resin-based sealers (AH Plus and Obtuseal). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure levels of trace elements (beryllium, magnesium, aluminium, calcium, chromium, arsenic and lead) in the brain, kidney and liver of rats. Twenty sterilized polyethylene tubes were then filled with AH Plus and Obtuseal and implanted into the dorsal subcutaneous tissue of 10 rats; three unoperated animals were used as a control group. After 45 days, the rats were sacrificed by cervical dislocation following anaesthesia, and brains, kidneys and livers were removed from all experimental animals. ICP-MS analysis was used to determine levels of trace elements. Data were analysed using Kruskal– Wallis and Connover post hoc tests. No significant differences were found in aluminium and calcium levels, but brains, kidneys and livers showed significantly higher amounts of magnesium and chromium than the corresponding controls. In the kidney and liver samples, arsenic levels were found to be higher than in the control group. Lead was detected at higher levels only in liver samples from the AH Plus group. Beryllium was not detected in any organ. It was concluded that AH Plus and Obtuseal release minimal quantities of trace elements when in contact with subcutaneous tissue, and further studies are needed to understand the systemic effects of these materials

  2. Protein synthesis in the growing rat lung

    International Nuclear Information System (INIS)

    Kelley, J.; Chrin, L.

    1986-01-01

    Developmental control of protein synthesis in the postnatal growth of the lung has not been systematically studied. In male Fischer 344 rats, lung growth continues linearly as a function of body weight (from 75 to 450 g body weight). To study total protein synthesis in lungs of growing rats, we used the technique of constant intravenous infusion of tritiated leucine, an essential amino acid. Lungs of sacrificed animals were used to determine the leucine incorporation rate into newly synthesized protein. The specific radioactivity of the leucine associated with tRNA extracted from the same lungs served as an absolute index of the precursor leucine pool used for lung protein synthesis. On the basis of these measurements, we were able to calculate the fractional synthesis rate (the proportion of total protein destroyed and replaced each day) of pulmonary proteins for each rat. Under the conditions of isotope infusion, leucyl-tRNA very rapidly equilibrates with free leucine of the plasma and of the extracellular space of the lung. Infusions lasting 30 minutes or less yielded linear rates of protein synthesis without evidence of contamination of lung proteins by newly labeled intravascular albumin. The fractional synthesis rate is considerably higher in juvenile animals (55% per day) than in adult rats (20% per day). After approximately 12 weeks of age, the fractional synthesis rate remains extremely constant in spite of continued slow growth of the lung. It is apparent from these data that in both young and adult rats the bulk of total protein synthesis is devoted to rapidly turning over proteins and that less than 4 percent of newly made protein is committed to tissue growth

  3. Reduced protein oxidation in Wistar rats supplemented with marine ω3 PUFAs.

    Science.gov (United States)

    Méndez, Lucía; Pazos, Manuel; Gallardo, José M; Torres, Josep L; Pérez-Jiménez, Jara; Nogués, Rosa; Romeu, Marta; Medina, Isabel

    2013-02-01

    The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on protein redox states from plasma, kidney, skeletal muscle, and liver were investigated in Wistar rats. Dietary fish oil groups were compared with animals fed soybean and linseed oils, vegetable oils enriched in ω6 linoleic acid (LA; 18:2) and ω3 α-linolenic acid (ALA; 18:3), respectively. Fish oil treatments were effective at reducing the level of total fatty acids in plasma and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Albumin was found to be the most carbonylated protein in plasma for all dietary groups, and its oxidation level was significantly modulated by dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed the lowest oxidation score for plasma albumin, followed in increasing order of carbonylation by 1:2 proteins and cytosolic proteins from kidney and liver also indicated a protective effect on proteins for the fish oil treatments, the 1:1 ratio exhibiting the lowest protein oxidation scores. The effect of fish oil treatments at reducing carbonylation on specific proteins from plasma (albumin), skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3-α-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights the efficiency of dietary fish oil at reducing in vivo oxidative damage of proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids ω3 ALA and ω6 LA, and such antioxidant activity may differ among different fish oil sources because of variations in EPA/DHA content. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

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    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  5. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats.

    Science.gov (United States)

    Silici, S; Doğan, Z; Sahin, H; Atayoğlu, T; Yakan, B

    2016-02-01

    The aim of the study is to evaluate the acute biochemical and histological changes in rat kidneys after treatment with grayanotoxin (GTX) of rhododendron honey (RH). A total of 60 Sprague-Dawley female rats were divided into five groups of 12 rats each, one being a control group (group 1) and group 2 was treated with 0.015 mg/kg/bw of GTX standard preparation via intraperitoneal injection. Groups 3, 4, and 5 were given RH at doses of 0.1, 0.5, and 2.5 g/kg/bw, respectively, via oral gavage. Compared to the control group, significant increases were observed in glucose, blood urea nitrogen (BUN), and creatinine levels of the GTX-injected groups after 1 h. However, in low dose RH group, such an increase was not observed and had a normal appearance histologically. Therefore, low dose (1 g/kg/bw) of RH produces no acute adverse effects on renal functions of rats.

  6. Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats

    OpenAIRE

    Stephen P. Chelko; Chad W. Schmiedt; Tristan H. Lewis; Tom P. Robertson; Stephen J. Lewis

    2014-01-01

    This study compared the contractile responses elicited by angiotensin II (AII), arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C) hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery) and distal segments (closer to the nodose ganglion) and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, hea...

  7. Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

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    Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare

    2015-01-01

    Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

  8. Methyl isobutyl ketone (MIBK) induction of α2u-globulin nephropathy in male, but not female rats

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Hard, G.C.; Berdasco, N.M.; Gingell, R.; Green, S.M.; Gulledge, W.

    2009-01-01

    Male F-344 rats were administered corn oil (vehicle control), d-limonene (positive control, 300 mg/kg), or MIBK (1000 mg/kg) and female F-344 rats corn oil (vehicle control) or MIBK for 10 consecutive days by oral gavage. Approximately 24 h after the final dose the kidneys were excised and the left kidney prepared and evaluated for histological changes including protein (hyaline) droplet accumulation, immunohistochemical staining for α2u-globulin (α2u), and proliferating cell nuclear antigen (PCNA) to quantitate renal cell proliferation. The right kidney was prepared for quantitation of total protein and α2u using an ELISA. MIBK elicited an increase in protein droplets, accumulation of α2u, and renal cell proliferation in male, but not female rats, responses characteristic of α2u-mediated nephropathy. MIBK produced identical histopathological changes in the male rat kidney when compared to d-limonene, an acknowledged inducer of α2u-nephropathy except that the grade of severity tended to be slightly lower with MIBK. MIBK did not induce any effects in female rats. Therefore, renal histopathology, along with the other measures of α2u accumulation, provides additional weight of evidence to support the inclusion of MIBK in the category of chemicals exerting renal effects through a α2u-nephropathy-mediated mode-of-action

  9. The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats

    International Nuclear Information System (INIS)

    Korish, Aida A.; Arafah, Maha M.

    2007-01-01

    Objective was to investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx). This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10 mg/kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA) and kidney functions were measured in all rats. Histopathological examination of kidney tissues was also performed. Untreated CRF rats showed significant elevation of plasma CRP, IL-6 and MDA levels and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, MDA levels and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats. Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histological damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease. (author)

  10. Genetic background of nonmutant Piebald-Virol-Glaxo rats does not influence nephronophthisis phenotypes

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    Yengkopiong JP

    2013-02-01

    Full Text Available Jada Pasquale Yengkopiong, Joseph Daniel Wani LakoJohn Garang Memorial University of Science and Technology, Faculty of Science and Technology, Bor, Jonglei State, Republic of South SudanBackground: Nephronophthisis (NPHP, which affects multiple organs, is a hereditary cystic kidney disease (CKD, characterized by interstitial fibrosis and numerous fluid-filled cysts in the kidneys. It is caused by mutations in NPHP genes, which encode for ciliary proteins known as nephrocystins. The disorder affects many people across the world and leads to end-stage renal disease. The aim of this study was to determine if the genetic background of the nonmutant female Piebald-Virol-Glaxo (PVG/Seac-/- rat influences phenotypic inheritance of NPHP from mutant male Lewis polycystic kidney rats.Methods: Mating experiments were performed between mutant Lewis polycystic kidney male rats with CKD and nonmutant PVG and Wistar Kyoto female rats without cystic kidney disease to raise second filial and backcross 1 progeny, respectively. Rats that developed cystic kidneys were identified. Systolic blood pressure was determined in each rat at 12 weeks of age using the tail and cuff method. After euthanasia, blood samples were collected and chemistry was determined. Histological examination of the kidneys, pancreas, and liver of rats with and without cystic kidney disease was performed.Results: It was established that the genetic background of nonmutant female PVG rats did not influence the phenotypic inheritance of the CKD from mutant male Lewis polycystic kidney rats. The disease arose as a result of a recessive mutation in a single gene (second filial generation, CKD = 13, non-CKD = 39, Χ2 = 0.00, P ≥ 0.97; backcross 1 generation, CKD = 67, non-CKD = 72, Χ2 = 0.18, P > 0.05 and inherited as NPHP. The rats with CKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia, but there were no extrarenal cysts and disease did not lead to

  11. The Expression Changes of Inflammasomes in the Aging Rat Kidneys.

    Science.gov (United States)

    Song, Fei; Ma, Yuxiang; Bai, Xue-Yuan; Chen, Xiangmei

    2016-06-01

    The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Inflammasomes are important components of innate immune system in the body. However, the function of inflammasomes and their underlying mechanisms in renal aging remain unclear. In this study, for the first time, we systematically investigated the role of the inflammasomes and the inflammatory responses activated by inflammasomes during kidney aging. We found that during kidney aging, the expression levels of the molecules associated with the activation of inflammasomes, including toll-like receptor-4 and interleukin-1 receptor (IL-1R), were significantly increased; their downstream signaling pathway molecule interleukin-1 receptor-associated kinase-4 (IRAK4) was markedly activated (Phospho-IRAK4 was obviously increased); the nuclear factor-κB (NF-κB) signaling pathway was activated (the activated NF-κB pathway molecules Phospho-IKKβ, Phospho-IκBα, and Phospho-NF-κBp65 were significantly elevated); the levels of the inflammasome components NOD-like receptor P3 (NLRP3), NLRC4, and pro-caspase-1 were prominently upregulated; and the proinflammatory cytokines IL-1β and IL-18 were notably increased in the kidneys of 24-month-old (elderly group) rats. These results showed that inflammasomes are markedly activated during the renal aging process and might induce inflamm-aging by promoting the maturation and secretion of the proinflammatory cytokines IL-1β and IL-18. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.

    Science.gov (United States)

    Kumar, Vikash; Wollner, Clayton; Kurth, Theresa; Bukowy, John D; Cowley, Allen W

    2017-10-01

    The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. We have previously demonstrated that H 2 O 2 is elevated in the kidneys of SS rats. The present study showed a significant upregulation of renal mTORC1 activity in the SS rats fed a 4.0% NaCl for 3 days. In addition, renal interstitial infusion of H 2 O 2 into salt-resistant Sprague Dawley rats for 3 days was also found to stimulate mTORC1 activity independent of a rise of arterial blood pressure. Together, these data indicate that the salt-induced increases of renal H 2 O 2 in SS rats activated the mTORC1 pathway. Daily administration of rapamycin (IP, 1.5 mg/kg per day) for 21 days reduced salt-induced hypertension from 176.0±9.0 to 153.0±12.0 mm Hg in SS rats but had no effect on blood pressure salt sensitivity in Sprague Dawley treated rats. Compared with vehicle, rapamycin reduced albumin excretion rate in SS rats from 190.0±35.0 to 37.0±5.0 mg/d and reduced the renal infiltration of T lymphocytes (CD3 + ) and macrophages (ED1 + ) in the cortex and medulla. Renal hypertrophy and cell proliferation were also reduced in rapamycin-treated SS rats. We conclude that enhancement of intrarenal H 2 O 2 with a 4.0% NaCl diet stimulates the mTORC1 pathway that is necessary for the full development of the salt-induced hypertension and kidney injury in the SS rat. © 2017 American Heart Association, Inc.

  13. Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

    Science.gov (United States)

    Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

    2014-07-01

    This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

  14. Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

    Science.gov (United States)

    Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

    2016-10-17

    Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Hydroxylation of 25-hydroxyvitamin D3 by renal mitochondria from rats of different ages.

    Science.gov (United States)

    Ishida, M; Bulos, B; Takamoto, S; Sacktor, B

    1987-08-01

    The hydroxylation of 25-hydroxyvitamin D3 (25OHD3) in kidney mitochondria from female rats of different ages was studied. The specific activity of 1 alpha-hydroxylase was highest in mitochondria isolated from the 2-month-old rat (0.47 pmol/10 min X mg protein), falling gradually with age to 0.17, 0.10, 0.07, and 0.06 pmol/10 min X mg protein in 6-, 12-, 18-, and 24-month-old rats, respectively. The alteration in 1 alpha-hydroxylase activity with age was due to a change in the V'm of the system; the K'm for 25OHD3 was unchanged (3.9-4.0 microM). The specific activity of 24-hydroxylase was lowest in mitochondria isolated from the 2-month-old rat (8.2 pmol/10 min X mg protein), increasing to 37.8, 37.4, 38.2, and 55.7 pmol/10 min X mg protein in 6-, 12-, 18-, and 24-month-old rats, respectively. The alteration in 24-hydroxylase activity with age was due to a change in the V'm of the system; the K'm value for 25OHD3 was unchanged (1.1-1.2 microM). The age-dependent decrease in 1 alpha-hydroxylase and concomitant increase in 24-hydroxylase activities observed in mitochondria isolated from kidneys of 2-, 6-, 12-, 18-, and 24-month-old rats could not be attributed to changes in the bioenergetic properties, i.e. the respiratory chain, of the mitochondria. The relative mitochondrial content of the kidney, however, probably decreased with age. These findings support the view that the kidneys of aged rats produce less 1,25-dihydroxyvitamin D3 because of lower mitochondrial 1 alpha-hydroxylase specific activity and reduced number of mitochondria. This would be consistent with the lower levels of vitamin D hormone reported in the serum of senescent rats.

  16. Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

    Science.gov (United States)

    Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

    2014-07-01

    The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

  17. Effect of Ethanolic Extract of Emblica officinalis on Histopathology of Kidney and on Biochemical Parameters in Hyperlipidemic Albino Rats

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    Bheemshetty S. Patil

    2015-01-01

    Full Text Available Background: It has been reported that hyperlipidemia plays a central role in the development of atherosclerosis and oxidative stress. Embilica officinalis also known as Amla or Indian Gooseberry acts as antihyperlipidemic and antioxidant. Its active ingredients contains tannins, gallic acid and flavonoids. Aim & Objectives: It was aimed to evaluate the effect of ethanolic extract of Emblica officinalis on histopathology of kidney and on biochemical parameters in hyperlipidemic albino Wistar rats. Material and Methods: Extraction of dried fruits of Emblica officinalis was done by Soxhlet apparatus 0 using 99% ethanol at 60 C for 24 hours and also phytochemical analysis was done. Group I served as normal control. Group II was fed with isocaloric diet. Group III was fed with hyperlipidemic diet. Group IV was fed with isocaloric diet for 21 days + Embilica officinalis for 21 days. Group V was fed with hyperlipidemic diet for 21 days+ Embilica officinalis for 21 days. The dose of ethanolic extract of Emblica officinalis was taken as 100mg/kg body weight daily. Results: Percent body weight gain, kidney weight and nephro-somatic index significantly improved in hyperlipidemic rats treated with Emblica officinalis. There was a significant improvement in serum electrolyte and kidney markers. It was found that there were focal glomerular lesions with thickening of glomerulus in the kidneys of rats on hyperlipidemic diet and normal renal histology of rats on hyperlipidemic diet treated with Emblica officinalis. Conclusion: It can be concluded that Emblica officinalis may be a good, natural therapeutic agent against hyperlipidemic diet induced oxidative damage and nephrotoxicity.

  18. The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

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    Cornock Ruth

    2010-08-01

    Full Text Available Abstract Background Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR and vasopressin-related aquaporins (AQP, hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. Methods Female Wistar rats were mated and fed a control (18% casein or low-protein (9% casein diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. Results As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals

  19. Twist2 Is Upregulated in Early Stages of Repair Following Acute Kidney Injury

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    Elizabeth A. Grunz-Borgmann

    2017-02-01

    Full Text Available The aging kidney is a marked by a number of structural and functional changes, including an increased susceptibility to acute kidney injury (AKI. Previous studies from our laboratory have shown that aging male Fischer 344 rats (24 month are more susceptible to apoptosis-mediated injury than young counterparts. In the current studies, we examined the initial injury and early recovery phases of mercuric chloride-induced AKI. Interestingly, the aging kidney had decreased serum creatinine compared to young controls 1 day following mercuric chloride injury, but by day 4, serum creatinine was significantly elevated, suggesting that the aging kidney did not recover from injury. This conclusion is supported by the findings that serum creatinine and kidney injury molecule-1 (Kim-1 gene expression remain elevated compared to young controls at 10 days post-injury. To begin to elucidate mechanism(s underlying dysrepair in the aging kidney, we examined the expression of Twist2, a helix-loop-helix transcription factor that may mediate renal fibrosis. Interestingly, Twist2 gene expression was elevated following injury in both young and aged rats, and Twist2 protein expression is elevated by mercuric chloride in vitro.

  20. 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim.

    Science.gov (United States)

    Salihu, Mariama; Ajayi, Babajide O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-01-01

    Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.

  1. Lithium induces microcysts and polyuria in adolescent rat kidney independent of cyclooxygenase-2

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2014-01-01

    In patients, chronic treatment with lithium leads to renal microcysts and nephrogenic diabetes insipidus (NDI). It was hypothesized that renal cyclooxygenase-2 (COX-2) activity promotes microcyst formation and NDI. Kidney microcysts were induced in male adolescent rats by feeding dams with lithium......, and inactive pGSK-3β in collecting duct; a blocker of COX-2 does not prevent cell proliferation, cyst formation, or GSK-3β inactivation. It is concluded that COX-2 activity is not the primary cause for microcysts and polyuria in a NaCl-substituted rat model of lithium nephropathy. COX-1 is a relevant candidate...

  2. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

    Science.gov (United States)

    Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

    2018-06-01

    Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

  3. Influence of electromagnetic field (1800 MHz on lipid peroxidation in brain, blood, liver and kidney in rats

    Directory of Open Access Journals (Sweden)

    Paweł Bodera

    2015-08-01

    Full Text Available Objectives: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min exposure to electromagnetic field (EMF of 1800 MHz frequency on tissue lipid peroxidation (LPO both in normal and inflammatory state, combined with analgesic treatment. Material and Methods: The concentration of malondialdehyde (MDA as the end-product of the lipid peroxidation (LPO was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund’s adjuvant (CFA-induced persistent paw inflammation. Results: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF. The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON, the exposed group (EMF, treated with tramadol (TRAM as well as exposed to and treated with tramadol (TRAM/EMF. In the group of animals treated with the complete Freund’s adjuvant (CFA we also observed slightly increased values of the MDA in the case of the control group (CON and the exposed groups (EMF and TRAM/EMF. The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. Conclusions: The electromagnetic field exposure (EMF, applied in the repeated manner together with opioid drug tramadol (TRAM, slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

  4. Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

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    Akira Marine

    2014-01-01

    Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

  5. Protein conjugated with aldehydes derived from lipid peroxidation as an independent parameter of the carbonyl stress in the kidney damage

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    Medina-Navarro Rafael

    2011-11-01

    Full Text Available Abstract Background One of the well-defined and characterized protein modifications usually produced by oxidation is carbonylation, an irreversible non-enzymatic modification of proteins. However, carbonyl groups can be introduced into proteins by non-oxidative mechanisms. Reactive carbonyl compounds have been observed to have increased in patients with renal failure. In the present work we have described a procedure designed as aldehyde capture to calculate the protein carbonyl stress derived solely from lipid peroxidation. Methods Acrolein-albumin adduct was prepared as standard at alkaline pH. Rat liver microsomal membranes and serum samples from patients with diabetic nephropathy were subjected to the aldehyde capture procedure and aldol-protein formation. Before alkalinization and incubation, samples were precipitated and redisolved in 6M guanidine. The absorbances of the samples were read with a spectrophotometer at 266 nm against a blank of guanidine. Results Evidence showed abundance of unsaturated aldehydes derived from lipid peroxidation in rat liver microsomal membranes and in the serum of diabetic patients with advanced chronic kidney disease. Carbonyl protein and aldol-proteins resulted higher in the diabetic nephropathy patients (p Conclusion The aldehyde-protein adduct represents a non oxidative component of carbonyl stress, independent of the direct amino acid oxidation and could constitute a practical and novelty strategy to measure the carbonyl stress derived solely from lipid peroxidation and particularly in diabetic nephropathy patients. In addition, we are in a position to propose an alternative explanation of why alkalinization of urine attenuates rhabdomyolysis-induced renal dysfunction.

  6. Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats

    Science.gov (United States)

    Rajeh, Nisreen A.; Al-Dhaheri, Najlaa M.

    2017-01-01

    Objectives: To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out. Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats. Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E PMID:28133684

  7. Microinjection study on potassium transport of rat kidney

    International Nuclear Information System (INIS)

    Miyamoto, Makoto

    1978-01-01

    Wister rate were divided into the following four groups. (A) control group (B) high-potassium diet group (C) low-potassium diet group (D) nephron population reduction (N.P.R.) group. Microinjection of the artificial solutions containing both 86 Rb and 3 H-inulin were performed into the proximal and distal convoluted tubules as well as cortical peritubular capillaries in rats undergoing mannitol diuresis. Excretory patterns of these substances were analyzed in successive urine samples. 3 H-inulin is entirely recovered in the urine of the experimental kidney following the injection into the proximal and distal tubules. 86 Rb is an adequate tracer for potassium and is absorbed into the potassium pool from either proximal tubular injections or peritubular capillaries. 86 Rb excreted with a time course similar to that of 3 H-inulin is termed as 'direct recovery' and that excreted more slowly, 'delayed recovery'. The 86 Rb recoveries which were obtained after proximal injections were independent of the injection site and averaged 9%. Secretion of 86 Rb into the urine was stimulate during enhanced K secretion and decreased during reduced K secretion along the distal nephron. Distal tubular injections gave 100% direct recovery in control, high-K diet, and N.P.R. rats. It was apparent that the 86 Rb recovery was significantly reduced, although not delayed, in animals deprived of dietary potassium for several weeks. At the collecting duct, the extensive net potassium reabsorption is observed in potassium depleted rats, whereas K absorption might be reduced or even secretion is seemingly taking place in potassium loading rats. In conclution, distal convolution and collecting duct play the major role in the regulation of urinary potassium excretion. (auth.)

  8. Nephrotoxicity of uranyl acetate: effect on rat kidney brush border membrane vesicles

    International Nuclear Information System (INIS)

    Goldman, M.; Yaari, A.; Moran, A.; Doshnitzki, Z.; Cohen-Luria, R.

    2006-01-01

    Since the Gulf war exposure to depleted uranium, a known nephrotoxic agent, there is a renewed interest in the toxic effects of uranium in general and its mechanism of nephrotoxicity which is still largely unknown in particular. In order to investigate the mechanism responsible for uranium nephrotoxicity and the therapeutic effect of urine alkalization, we utilized rat renal brush border membrane vesicles (BBMV). Uranyl acetate (UA) caused a decrease in glucose transport in BBMV. The apparent K i of uranyl was 139±30 μg uranyl/mg protein of BBMV. Uranyl at 140 μg/mg protein of BBMV reduced the maximal capacity of the system to transport glucose [V max 2.2±0.2 and 0.96±0.16 nmol/mg protein for control and uranyl treated BBMV (P m (1.54±0.33 and 1.54±0.51 mM for control, and uranyl treated BBMV, respectively). This reduction in V max is at least partially due to a decrease in the number of sodium-coupled glucose transporters as apparent from the reduction in phlorizin binding to the uranyl treated membranes, V max was reduced from 247±13 pmol/mg protein in control BBMV to 119±3 pmol/mg protein in treated vesicles (P<0.001). The pH of the medium has a profound effect on the toxicity of UA on sodium-coupled glucose transport in BBMV: higher toxicity at neutral pH (around pH 7.0), and practically no toxicity at alkaline pH (7.6). This is the first report showing a direct inhibitory dose and pH dependent effect of uranyl on the glucose transport system in isolated apical membrane from kidney cortex. (orig.)

  9. Physiological effects of some synthetic food colouring additives on rats.

    Science.gov (United States)

    Aboel-Zahab, H; el-Khyat, Z; Sidhom, G; Awadallah, R; Abdel-al, W; Mahdy, K

    1997-11-01

    Three different synthetic chocolate colourant agents (A, B and C) were administered to healthy adult male albino rats for 30 and 60 day periods to evaluate their effects on body weight, blood picture, liver and kidney functions, blood glucose, serum and liver lipids, liver nucleic acids (DNA and RNA), thyroid hormones (T3 and T4) and growth hormone. In addition, histopathological examinations of liver, kidney and stomach sections were studied. These parameters were also investigated 30 days after colourant stoppage (post effect). Ingestion of colourant C (brown HT and indigocarmine) significantly decreased rat body weight, serum cholesterol and HDL-cholesterol fraction, while, T4 hormone, liver RNA content, liver enzymes (S. GOT, S. GPT and alkaline phosphatase), total protein and globulin fractions were significantly elevated. Significant increases were observed in serum total lipids, cholesterol, triglycerides, total protein, globulin and serum transaminases in rats whose diets were supplemented with chocolate colours A and B (sunset yellow, tartrazine, carmoisine and brilliant blue in varying concentrations). Haematological investigations demonstrated selective neutropenia and lymphocytosis with no significant alterations of total white blood cell counts in all rat groups, while haemoglobin concentrations and red blood cell counts were significantly decreased in the rats who were administered food additives A and B. Eosinophilia was noted in rats fed on colourant A only. No changes were recorded for blood glucose, growth hormone and kidney function tests. Histopathological studies showed brown pigment deposition in the portal tracts and Van Küpffer cells of the liver as well as in the interstitial tissue and renal tubular cells of the kidney mainly induced by colourant A. Congested blood vessels and areas of haemorrhage in both liver and renal sections were revealed in those rats who were given colourants B and C. There were no-untoward-effects recorded in the

  10. Effects of Qiangji Jianli Yin on the hypothalamus CRH contents and plasma ACTH, cortisol levels in rat models of kidney-yang deficiency syndrome

    International Nuclear Information System (INIS)

    Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou

    2007-01-01

    Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)

  11. Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.

    Science.gov (United States)

    Yuan, Fang; Liu, Ying-Hong; Liu, Fu-You; Peng, You-Ming; Tian, Jun-Wei

    2014-06-01

    The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

  12. Sweet potato Ipomoea Batatas Modulates Radiation-induced Oxidative damage in Liver and kidney of Male Albino Rats

    International Nuclear Information System (INIS)

    Darwish, M. M.; Farag, M. F. S.; Osman, N. N.

    2010-01-01

    Sweet potato Ipomoea Batatas, one of the major vegetable crops consumed worldwide, is rich in phytochemicals, which displayed antioxidant activities. This work aims at assessing the radio-protective properties of sweet potato tubers on liver and kidney tissues. Male albino rats were whole body exposed to 0.5 Gy day after day for a period of 20 days. Animal received orally prepared aqueous extract of sweet potato tubers (100 mg kg/body weight), one week before irradiation and during the period of radiation exposure. The results demonstrated that irradiation of rats induced a significant increase in lipid peroxides level measured as thiobarbituric acid reactive substances (TBARS) concomitant with a significant decrease in superoxide dismutase (SOD), and catalase (CAT) activity and glutathione (GSH) content in liver and kidney tissues. Administration of a freshly prepared aqueous extract of sweet potato tubers to rats, one week pre-irradiation and during the period of radiation exposure has significantly of ameliorated the oxidative stress in both tissues. The significant amelioration in oxidative stress was substantiated by improvement of liver and kidney enzymes Treatment of rats with sweet potato has significantly reduced the increase in serum alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) activity, serum creatinine and urea levels. Furthermore, hyperglycemia and alteration in lipid profile manifested by a significant increase in triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), and a significant decrease in high density lipoprotein cholesterol (HDL-C), were improved in sweet potato-treated irradiated rats compared to those only irradiated. According to the results obtained in the present study, it could be concluded that sweet potato through its antioxidant activities could protect cellular membrane from radiation induced oxidative damage in animals and preserve the

  13. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

    Directory of Open Access Journals (Sweden)

    Zoran Miloradović

    2014-01-01

    Full Text Available Acute kidney injury (AKI is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance P<0.05 compared to AKI control. It also increased cardiac output and catalase activity P<0.05. Lipid peroxidation and renal vascular resistance were decreased in TEMPOL P<0.05. Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2− scavenging.

  14. Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells.

    Science.gov (United States)

    Liu, Man; Gao, Bo-Yan; Qin, Fang; Wu, Ping-Ping; Shi, Hai-Ming; Luo, Wei; Ma, Ai-Niu; Jiang, Yuan-Rong; Xu, Xue-Bing; Yu, Liang-Li Lucy

    2012-10-01

    The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1-monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined 2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate dose-dependently decreased the mean body weight, and caused significant increase of serum urea nitrogen and creatinine in dead mice compared to the control and survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate were renal tubular necrosis, protein casts and spermatids decrease in the seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50 value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW. Obvious changes were not observed on mean body weight, absolute and relative organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD dipalmitate. However, renal tubular necrosis, protein casts and spermatids decrease were also observed in the dead mice. In addition, MTT and LDH assay results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat kidney cells in a dose-dependent manner. Together, the results indicated a greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats.

    Science.gov (United States)

    Nakata, Hokuto; Nakayama, Shouta M M; Oroszlany, Balazs; Ikenaka, Yoshinori; Mizukawa, Hazuki; Tanaka, Kazuyuki; Harunari, Tsunehito; Tanikawa, Tsutomu; Darwish, Wageh Sobhy; Yohannes, Yared B; Saengtienchai, Aksorn; Ishizuka, Mayumi

    2017-01-10

    Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown ( Rattus norvegicus , n = 43) and black ( R. rattus , n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed.

  16. Tubular kidney injury molecule-1 in protein-overload nephropathy

    NARCIS (Netherlands)

    van Timmeren, Mirjan M.; Bakker, Stephan J. L.; Vaidya, Vishal S.; Bailly, Veronique; Schuurs, Theo A.; Damman, Jeffrey; Stegeman, Coen A.; Bonventre, Joseph V.; van Goor, Harry

    Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and

  17. Ingestion of dug well water from an area with high prevalence of chronic kidney disease of unknown etiology (CKDu) and development of kidney and liver lesions in rats

    Science.gov (United States)

    Thammitiyagodage, M G; Gunatillaka, M M; Ekanayaka, N; Rathnayake, C; Horadagoda, N U; Jayathissa, R; Gunaratne, U K; Kumara, W G; Abeynayake, P

    2017-03-31

    Chronic kidney disease of unknown aetiology (CKDu) is prevalent in the North Central Province (NCP) of Sri Lanka and ingestion of dug well water is considered a potential causative factor. Three CKDu prevalent villages were selected from the NCP based on the number of CKDu patients in the locality. Forty Wistar rats were divided into four groups with 10 rats each. Group No 1, 2 and 3 were given water from selected dug wells. Control group was given tap water from Colombo. Water samples were analysed for fluoride, iron, arsenic, cadmium and calcium. Histopathological examination of liver and kidney tissues were performed. Significant reduction of glomerular filtration rate (GFR) was observed in two test groups compared to the control group (p0.05). In one group hepatocellular carcinoma with elevated serum liver enzymes was observed whilst hepatitis was observed in another test group (p<0.05). But mixed lesions were common in all affected rats. Significantly high renal tubular lesion index was observed in all three experimental groups (p<0.05) and high glomerular lesion index (p=0.017) was observed in one test group. Cadmium, arsenic and iron contents were below detectable levels in the NCP water sources and tap water from Colombo. Different wells may have different concentrations of environmental toxins and depending on the severity of the toxin contents GFR and grade and type of liver and kidney lesions may vary. High fluoride and other undetected toxins in shallow dug wells may be the causative factors for renal and liver lesions in these Wistar rats.

  18. Effect of triiodothyronine on rat liver chromatin protein kinase

    International Nuclear Information System (INIS)

    Kruh, J.; Tichonicky, L.

    1976-01-01

    1) Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2) Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32 P when incubated with [γ- 32 P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32 P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins. (orig.) [de

  19. Effect of omnivorous and vegan diets with different protein and carbohydrate content on growth and metabolism of growing rats.

    Science.gov (United States)

    Giuberti, Gianluca; Morlacchini, Mauro; Crippa, Luca; Capraro, Jessica; Paganini, Beatrice; Gallo, Antonio; Rossi, Filippo

    2018-08-01

    The purpose of this study was to observe, in a rat animal model, the short and medium term effects of vegan (VEG) or omnivorous (OMNI) diets with different energy partition between nutrients (zone or classic). Six different diets were administered, for 72 days to 120 growing male Sprague-Dawley rats: (i) VEG zone diet; (ii) VEG classic diet; (iii) OMNI zone diet; (iv) OMNI classic diet; (v) OMNI zone diet with added fibre and (vi) OMNI classic diet with added fibre. Zone diets (high protein and low carbohydrates), resulted in better growth , feed efficiency, lower blood glucose and insulin responses. VEG diets have lowered cholesterol blood level. Histopathological analysis evidenced no damage to liver and kidney tissue by the intake of any of the diet types. Further longer animal and human duration studies should be performed to exclude detrimental effect of higher protein diet.

  20. Molecular characterization of a rat α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    Zeng, D.; Harrison, J.K.; D'Angelo, D.D.; Barber, C.M.; Tucker, A.L.; Lu, Z.; Lynch, K.R.

    1990-01-01

    α 2 -Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNGα 2 ) encoding a rat α 2 -adrenergic receptor. A rat kidney cDNA library was screened with an oligonucleotide complementary to a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of guanyl nucleotide-binding protein-coupled receptors except it does not have a consensus N-linked glycosylation site near the amino terminus. Membranes prepared from COS cells transfected with pRNGα 2 DNA display high affinity an saturable binding to [ 3 H]rauwolscine. Competition curve data analysis shows that RNGα 2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine ≥ chlorpromazine > prazosin ≥ clonidine > norepinephrine ≥ oxymetazoline. RNGα 2 RNA accumulates in both rat kidney and neonatal rat lung. When a cysteine residue (Cys-169) that is conserved among all members of the seven-transmembrane-region superfamily is changed to phenylalanine, the RNGα 2 protein fails to bind [ 3 H]rauwolscine after expression in COS cells. They conclude that pRNGα 2 likely represents a cDNA for a rat α 2B -adrenergic receptor

  1. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of doxorubicin through intravenous administration in rats.

    Directory of Open Access Journals (Sweden)

    Kishore Golla

    Full Text Available Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC. The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity.Doxorubicin loaded apotransferrin (Apodoxonano and lactoferrin nanoparticles (Lactodoxonano were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers.In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g. Both nanoformulations showed higher localization compared to doxorubicin (Doxo when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g, suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation.Drug delivery through nanoformulations not only minimizes the cardiotoxicity of

  2. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    Science.gov (United States)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  3. Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

    Directory of Open Access Journals (Sweden)

    Sotiria Palimeri

    2016-06-01

    Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen exposure, exert a more profound negative impact on the kidney of an androgenized female rat model that mimics the metabolic characteristics of polycystic ovary syndrome.

  4. [Impacts of the formula of Suoquanwan(SQW) on expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency].

    Science.gov (United States)

    Cao, Hong-Ying; Wu, Qing-He; Huang, Ping; He, Jin-Yang

    2009-06-01

    To observe the impacts of the formula of Suoquanwan (SQW) on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency. The model rats were induced by adenine (250 mg/kg) for 4 weeks, then treated respectively with SQW or dDAVP. The expression of AQP-2 mRNA and AVPR-V2 mRNA in kidney of Yang-deficiency model by realtime fluorescence quantitative PCR method were investigated. In model rats, the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney decreased, dDAVP and SQW high dose could increased the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. The others had no influence on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. SQW can increase the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency.

  5. Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats

    NARCIS (Netherlands)

    Steinmetz, O. M.; Sadaghiani, S.; Panzer, U.; Krebs, C.; Meyer-Schwesinger, C.; Streichert, T.; Fehr, S.; Hamming, I.; van Goor, H.; Stahl, R. A. K.; Wenzel, U.

    The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure

  6. Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.

    Science.gov (United States)

    Zhang, Bo; Tran, Uyen; Wessely, Oliver

    2018-03-22

    The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in polycystic kidney disease (PKD), resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein-coupled signaling in the Xenopus pronephric kidney, we discovered that loss of the G-protein α subunit, Gnas, results in a PKD phenotype. Polycystin 1, one of the genes mutated in human PKD, encodes a protein resembling a G-protein-coupled receptor. Furthermore, deletion of the G-protein-binding domain present in the intracellular C terminus of polycystin 1 impacts functionality. A comprehensive analysis of all the G-protein α subunits expressed in the Xenopus pronephric kidney demonstrates that polycystin 1 recruits a select subset of G-protein α subunits and that their knockdown - as in the case of Gnas - results in a PKD phenotype. Mechanistically, the phenotype is caused by increased endogenous G-protein β/γ signaling and can be reversed by pharmacological inhibitors as well as knocking down Gnb1. Together, our data support the hypothesis that G proteins are recruited to the intracellular domain of PKD1 and that this interaction is crucial for its function in the kidney. © 2018. Published by The Company of Biologists Ltd.

  7. Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59.

    Science.gov (United States)

    Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

    2017-09-01

    To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an

  8. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

    Science.gov (United States)

    Ziamajidi, Nasrin; Nasiri, Abolfazl; Abbasalipourkabir, Roghayeh; Sadeghi Moheb, Somayeh

    2017-12-01

    Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p garlic-treated diabetic rats compared with diabetic rats (p garlic, it was close to the normal level (p garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

  9. Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

    International Nuclear Information System (INIS)

    Barac-Nieto, M.; Lui, S.M.; Spitzer, A.

    1991-01-01

    Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats

  10. Effect of administration of high-protein diet in rats submitted to resistance training.

    Science.gov (United States)

    da Rosa Lima, Thiago; Ávila, Eudes Thiago Pereira; Fraga, Géssica Alves; de Souza Sena, Mariana; de Souza Dias, Arlyson Batista; de Almeida, Paula Caroline; Dos Santos Trombeta, Joice Cristina; Junior, Roberto Carlos Vieira; Damazo, Amílcar Sabino; Navalta, James Wilfred; Prestes, Jonato; Voltarelli, Fabrício Azevedo

    2018-04-01

    Although there is limited evidence regarding the pathophysiological effects of a high-protein diet (HD), it is believed that this type of diet could overload the body and cause damage to the organs directly involved with protein metabolism and excretion. The aim of this study was to verify the effects of HD on biochemical and morphological parameters of rats that completed a resistance training protocol (RT; aquatic jump) for 8 weeks. Thirty-two adult male Wistar rats were divided into four groups (n = 8 for each group): sedentary normal protein diet (SN-14%), sedentary high-protein diet (SH-35%), trained normal protein diet (TN-14%), and trained high-protein diet (TH-35%). Biochemical, tissue, and morphological measurements were made. Kidney (1.91 ± 0.34) and liver weights (12.88 ± 1.42) were higher in the SH. Soleus muscle weight was higher in the SH (0.22 ± 0.03) when compared to all groups. Blood glucose (123.2 ± 1.8), triglycerides (128.5 ± 44.0), and HDL cholesterol levels (65.7 ± 20.9) were also higher in the SH compared with the other experimental groups. Exercise reduced urea levels in the trained groups TN and TH (31.0 ± 4.1 and 36.8 ± 6.6), respectively. Creatinine levels were lower in TH and SH groups (0.68 ± 0.12; 0.54 ± 0.19), respectively. HD negatively altered renal morphology in SH, but when associated with RT, the apparent damage was partially reversed. In addition, the aquatic jump protocol reversed the damage to the gastrocnemius muscle caused by the HD. A high-protein diet promoted negative metabolic and morphological changes, while RT was effective in reversing these deleterious effects.

  11. Effect of dental materials on gluconeogenesis in rat kidney tubules

    Energy Technology Data Exchange (ETDEWEB)

    Reichl, F.X.; Durner, J.; Mueckter, H.; Elsenhans, B.; Forth, W. [Muenchen Univ. (Germany). Walter-Straub-Institut fuer Pharmakologie und Toxikologie; Kunzelmann, K.H.; Hickel, R. [Department of Operative/Restorative Dentistry, Periodontology and Pedodontics, Ludwig-Maximilians-University of Munich (Germany); Spahl, W. [Institute of Organic Chemistry, Ludwig-Maximilians-University of Munich (Germany); Hume, W.R. [Dental Research Institute, Univ. of California, Los Angeles, CA (United States); Moes, G.W. [TNO Prins-Maurits-Laboratorium, Rijswijk (Netherlands)

    1999-09-01

    The effect of dental composite components triethyleneglycoldimethacrylate (TEGDMA) and hydroxyethylmethacrylate (HEMA) as well as mercuric chloride (HgCl{sub 2}) and methylmercury chloride (MeHgCl) on gluconeogenesis was investigated in isolated rat kidney tubules. From starved rats kidney tubules were prepared and isolated by digestion with collagenase. Every 10 min up to 60 min 1-ml samples were drawn from the cell suspension for quantitating the glucose content. Glucose formation in controls was 3.3 {+-} 0.2 nmol/mg . per min (mean {+-} SEM, n=21). Relative rates of glucose formation were obtained by expressing individual rates as a percentage of the corresponding control. X-Y concentration curves (effective concentration, EC) of the substances were calculated by fitting a four-parametric sigmoid function to the relative rates of glucose formation at various test concentrations. At the end of the incubation period cell viability was assessed by trypan blue exclusion. Cell viability decreased within the 60 min interval from 90 to approx. 80% (controls), <25 (HEMA), <20 (TEGDMA), <10 (MeHgCl), and <10% (HgCl{sub 2}). Values of 50% effective concentration (EC{sub 50}) were calculated from fitted curves. EC{sub 50} values were (mmol; mean {+-} SEM; n=4): HEMA, 17.7 {+-} 2.9; TEGDMA, 1.8 {+-} 0.2; MeHgCl, 0.018 {+-} 0.0005; and HgCl{sub 2}, 0.0016 {+-} 0.0005. The toxic effect of HgCl{sub 2} was {proportional{underscore}to}1000 or 10 000 higher than that of the dental composite components TEGDMA or HEMA, respectively. (orig.)

  12. Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

    International Nuclear Information System (INIS)

    Jakobsson, B.; el Hag, I.A.; Andersson, M.; Christensson, P.I.; Stenram, U.

    1990-01-01

    Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes

  13. Ontogeny and nutritional programming of mitochondrial proteins in the ovine kidney, liver and lung.

    Science.gov (United States)

    Yakubu, D P; Mostyn, A; Hyatt, M A; Kurlak, L O; Budge, H; Stephenson, T; Symonds, M E

    2007-12-01

    This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term approximately 147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.

  14. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    International Nuclear Information System (INIS)

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of [ 14 C]valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements

  15. Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.

    Science.gov (United States)

    Prohaska, Joseph R; Broderius, Margaret; Brokate, Bruce

    2003-09-15

    Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.

  16. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-01-01

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into

  17. Protein and energy intake in advanced chronic kidney disease: how much is too much?

    Science.gov (United States)

    Ikizler, T Alp

    2007-01-01

    Uremic wasting is strongly associated with increased risk of death and hospitalization events in patients with advanced chronic kidney disease (CKD). Recent evidence indicates that patients with advanced chronic kidney disease are prone to uremic wasting due to several factors, which include the dialysis procedure and certain comorbid conditions, especially chronic inflammation and insulin resistance or deficiency. While the catabolic effects of dialysis can be readily avoided with intradialytic nutritional supplementation, there are no established alternative strategies to avoid the catabolic consequences of comorbid conditions other than treatment of their primary etiology. To this end, there is no indication that simply increasing dietary protein and energy intake above the required levels based on level of kidney disease is beneficial in patients with advanced chronic kidney disease. However, aside from the potential adverse effects such as uremic toxin production, dietary protein and energy intake in excess of actual needs might be beneficial in maintenance dialysis patients as it may lead to weight gain over time. Clearly, the role of obesity in advanced uremia needs to be examined in detail prior to making any clinically applicable recommendations, both in terms of ''low'' and ''high'' dietary protein and energy intake.

  18. Green asparagus (Asparagus officinalis) prevented hypertension by an inhibitory effect on angiotensin-converting enzyme activity in the kidney of spontaneously hypertensive rats.

    Science.gov (United States)

    Sanae, Matsuda; Yasuo, Aoyagi

    2013-06-12

    Green asparagus (Asparagus officinalis) is known to be rich in functional components. In the present study, spontaneously hypertensive rats (SHR) were used to clarify whether green asparagus prevents hypertension by inhibition of angiotensin-converting enzyme (ACE) activity. Six-week-old male SHR were fed a diet with (AD group) or without (ND group) 5% asparagus for 10 weeks. Systolic blood pressure (SBP) (AD: 159 ± 4.8 mmHg, ND: 192 ± 14.7 mmHg), urinary protein excretion/creatinine excretion, and ACE activity in the kidney were significantly lower in the AD group compared with the ND group. Creatinine clearance was significantly higher in the AD group compared with the ND group. In addition, ACE inhibitory activity was observed in a boiling water extract of asparagus. The ACE inhibitor purified and isolated from asparagus was identified as 2″-hydroxynicotianamine. In conclusion, 2″-hydroxynicotianamine in asparagus may be one of the factors inhibiting ACE activity in the kidney, thus preventing hypertension and preserving renal function.

  19. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    International Nuclear Information System (INIS)

    Com, Emmanuelle; Boitier, Eric; Marchandeau, Jean-Pierre; Brandenburg, Arnd; Schroeder, Susanne; Hoffmann, Dana; Mally, Angela; Gautier, Jean-Charles

    2012-01-01

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic

  20. Increased Milk Protein Concentration in a Rehydration Drink Enhances Fluid Retention Caused by Water Reabsorption in Rats.

    Science.gov (United States)

    Ito, Kentaro; Saito, Yuri; Ashida, Kinya; Yamaji, Taketo; Itoh, Hiroyuki; Oda, Munehiro

    2015-01-01

    A fluid-retention effect is required for beverages that are designed to prevent dehydration. That is, fluid absorbed from the intestines should not be excreted quickly; long-term retention is desirable. Here, we focused on the effect of milk protein on fluid retention, and propose a new effective oral rehydration method that can be used daily for preventing dehydration. We first evaluated the effects of different concentrations of milk protein on fluid retention by measuring the urinary volumes of rats fed fluid containing milk protein at concentrations of 1, 5, and 10%. We next compared the fluid-retention effect of milk protein-enriched drink (MPD) with those of distilled water (DW) and a sports drink (SD) by the same method. Third, to investigate the mechanism of fluid retention, we measured plasma insulin changes in rats after ingesting these three drinks. We found that the addition of milk protein at 5 or 10% reduced urinary volume in a dose-dependent manner. Ingestion of the MPD containing 4.6% milk protein resulted in lower urinary volumes than DW and SD. MPD also showed a higher water reabsorption rate in the kidneys and higher concentrations of plasma insulin than DW and SD. These results suggest that increasing milk protein concentration in a beverage enhances fluid retention, which may allow the possibility to develop rehydration beverages that are more effective than SDs. In addition, insulin-modifying renal water reabsorption may contribute to the fluid-retention effect of MPD.

  1. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  2. Early postnatal gentamicin and ceftazidime treatment in normal and food restricted neonatal wistar rats: Implications for kidney development.

    Science.gov (United States)

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Brüggemann, Roger J M; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2017-09-01

    Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were studied in a separate group of animals. Kidneys were weighed. Renal expression of 18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35, glomerular number was assessed by stereology and glomerular generations were counted. Food restricted litters showed 22% less body weight compared with controls by day 35 (p kidney development, ceftazidime can affect Renin expression, and extrauterine growth restriction impairs kidney development, but did not modulate potential drug toxicity. Birth Defects Research 109:1228-1235, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Altered Regulation of type 3 Na+/H+ exchanger, type 1 Na+/HCO3- cotransporter, and Na+,K+-ATPase in the Kidney of Rats with Experimental Rhabdomyolysis

    Science.gov (United States)

    Ma, Seong Kwon; Bae, Eun Hui; Lee, JongUn; Kim, Sun Young; Kim, Sung Zoo; Choi, Ki Chul

    2007-01-01

    Metabolic acidosis was shown to correlate with deterioration of renal function in patients with rhabdomyolysis. The present study was aimed to investigate whether the changes of type 3 Na+/H+ exchanger (NHE3), type 1 Na+/HCO3- cotransporter (NBC1), and Na+,K+-ATPase α1 subunit may play a role in the pathogenesis of metabolic acidosis in glycerol-induced experimental rhabdomyolysis. Male Sprague-Dawley rats were deprived of fluid intake for 24 hours, and then were injected with 50% glycerol in normal saline (10 mL/kg, intramuscularly). At 24 hours after the glycerol injection, rats were sacrificed by decapitation. Control rats were injected with normal saline. The protein expression of NHE3, NBC1 and Na+,K+-ATPase α1 subunit was determined in the cortex of the kidney by immunoblotting and immunohistochemistry. Following the treatment of glycerol, creatinine clearance was significantly decreased, and high anion gap metabolic acidosis developed. In the experimental group, the expression of Na+,K+-ATPase α1 subunit was significantly decreased in the cortex of the kidney. On the contrary, the expression of NHE3 and NBC1 was significantly increased. Immunohistochemical analyses confirmed the immunoblotting data. In conclusion, the coordinate up-regulation of NHE3 and NBC1 may play an adaptive role against the metabolic acidosis in glycerol-induced rhabdomyolysis. PMID:24459502

  4. Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Wei-Jun Huang

    2018-01-01

    Full Text Available Qufengtongluo (QFTL decoction is an effective treatment for diabetic nephropathy (DN. However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-β, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-β mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-β was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-β.

  5. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression

    Directory of Open Access Journals (Sweden)

    Hua Chen

    2016-12-01

    Full Text Available Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN rats at week 24, adenine-induced chronic kidney disease (CKD rats and CKD patients. Compared with control rats, AAN rats showed anemia, increased serum urea and creatinine, progressive renal interstitial fibrosis, activation of nuclear factor-kappa B, and up-regulation of pro-inflammatory, pro-oxidant, and pro-fibrotic proteins at weeks 8 and 12. However, no significant difference was found at week 4. Metabolomics identified 12-ketodeoxycholic acid, taurochenodesoxycholic acid, LPC(15:0 and docosahexaenoic acid as biomarkers for early detection of tubulo-interstitial nephropathy. With prolonging aristolochic acid I exposure, LPE(20:2, cholic acid, chenodeoxycholic acid and LPC(17:0 were identified as biomarkers for progression from early to advanced AAN and lysoPE(22:5, indoxyl sulfate, uric acid and creatinine as biomarkers of advanced AAN. These biomarkers were reversed by treatment of irbesartan and ergone in AAN rats at week 24 and adenine-induced CKD rats. In addition, these biomarkers were also reversed by irbesartan treatment in CKD patients.

  6. [Changing laws of serum high mobility group box 1 protein in septic rats and the intervention effect of xuebijing].

    Science.gov (United States)

    Zhao, Shi-bing; He, Xian-di; Wang, Hua-xue; Zheng, Sheng-yong; Deng, Xi-ming; Duan, Li-bin

    2014-06-01

    To investigate the changing laws of serum high mobility group box 1 protein (HMGB1) in septic rats and intervention effect of Xuebijing on it. Lipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing treatment group (C, n=30). Rats in the C group were further divided into three subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood samples were collected from the caudal vein to detect serum HMGB1 levels by Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30 Wistar rats were equally divided into the LPS model group (D) and the LPS + Xuebijing treatment group (E), 15 in each group. They were treated as rats in the B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and 48 h after LPS injection in the two groups. Blood as well as the tissue samples were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as pathological changes of liver, lung, and kidney. (1) Compared with the A group, serum HMGB1 levels were higher at various time points in the B group (P decrement in the C3 group was less than that in the C1 and C2 groups (P multiple organ dysfunction. Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters, and attenuate severe inflammatory response of liver, lung, and kidney tissues in septic rats. Besides, the earlier use, the better effect obtained.

  7. Vitamin K metabolism in a rat model of chronic kidney disease

    Science.gov (United States)

    Background: Patients with chronic kidney disease (CKD) have very high levels of uncarboxylated, inactive, extra-hepatic vitamin K-dependent proteins measured in circulation, putting them at risk for complications of vitamin K deficiency. The major form of vitamin K found in the liver is phylloquinon...

  8. A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng.

    Science.gov (United States)

    Park, Sok; Kim, Chan-Sik; Min, Jinah; Lee, Soo Hwan; Jung, Yi-Sook

    2014-01-01

    Declining renal function is commonly observed with age. Obesity induced by a high-fat diet (HFD) may reduce renal function. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and have an anti-aging effect. This study was designed to investigate whether HFD would accelerate the D-galactose-induced aging process in the rat kidney and to examine the preventive effect of KRG on HFD and D-galactose-induced aging-related renal injury. When rats with D-galactose-induced aging were fed an HFD for 9 wk, enhanced oxidative DNA damage, renal cell apoptosis, protein glycation, and extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage, were observed in renal glomerular cells and tubular epithelial cells. However, treatment of rats with HFD- plus D-galactose-induced aging with KRG restored all of these renal changes. Our data suggested that a long-term HFD may enhance D-galactose-induced oxidative renal injury in rats and that this age-related renal injury could be suppressed by KRG through the repression of oxidative injury.

  9. Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys.

    Science.gov (United States)

    He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M

    2017-08-01

    Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.

  10. Lead nitrate induced unallied expression of liver and kidney functions in male albino rats.

    Science.gov (United States)

    Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

    2005-06-01

    To determine the effects of lead where lead accumulates maximum (liver followed by kidney), liver and kidney functions were studied using low oral dose of lead nitrate for prolonged duration. Dose of 20 mg lead nitrate/kg body wt/day was used in male albino rats. AST and ALT levels altered independently. When ALT remained unaltered after 7 and 21 days of treatment, it is decreased by 13.21% after 14 days treatment. AST was marginally lowered after 7 days, increased after 14 days and increased marginally after 21 days. Bilirubin (conjugated, unconjugated and total) decreased after 7 and 14 days and increased after 21 days. Urea increase was directly proportional to duration. Creatinine remained unaltered.

  11. Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia.

    Science.gov (United States)

    Mace, Maria L; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa

    2017-07-01

    Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats.

    Science.gov (United States)

    Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Robertson, Tom P; Lewis, Stephen J

    2014-01-01

    This study compared the contractile responses elicited by angiotensin II (AII), arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C) hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery) and distal segments (closer to the nodose ganglion) and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, heart rates, and plasma renin concentrations than SHAM rats. The contractile responses to AII were markedly diminished in both proximal and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats. The responses elicited by AVP were substantially greater in distal than in proximal segments of OAs from SHAM rats and that AVP elicited similar responses in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate that continued exposure to circulating AII and AVP in 2K-1C rats reduces the contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to AII may alter the physiological status of OAs in vivo.

  13. Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats

    Directory of Open Access Journals (Sweden)

    Stephen P. Chelko

    2014-01-01

    Full Text Available This study compared the contractile responses elicited by angiotensin II (AII, arginine vasopressin (AVP, and 5-hydroxytryptamine (5-HT in isolated occipital arteries (OAs from sham-operated (SHAM and 2-kidney, 1-clip (2K-1C hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery and distal segments (closer to the nodose ganglion and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, heart rates, and plasma renin concentrations than SHAM rats. The contractile responses to AII were markedly diminished in both proximal and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats. The responses elicited by AVP were substantially greater in distal than in proximal segments of OAs from SHAM rats and that AVP elicited similar responses in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate that continued exposure to circulating AII and AVP in 2K-1C rats reduces the contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to AII may alter the physiological status of OAs in vivo.

  14. [Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons].

    Science.gov (United States)

    Starek, A; Kamiński, M

    1982-01-01

    The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

  15. Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Starek, A.; Kaminski, M.

    1982-01-01

    The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

  16. [Retrospective analysis of influence of differential protein intake on renal prognosis for progressive chronic kidney disease].

    Science.gov (United States)

    Dai, Wendi; Yin, Daoxin; Cui, Wenying; Liu, Wenhu

    2014-01-28

    To explore retrospectively the influence of differential protein intake on renal prognosis for progressive chronic kidney disease (CKD). A total of 159 chronic kidney disease patients at stages 2, 3 and 4 were enrolled and a questionnaire survey was conducted from January 2009 to July 2012. They were followed monthly and their clinical data collected, including primary disease, blood pressure, body mass index and adverse events. Laboratory tests were performed every 3 months, including biochemical parameters, protein-energy malnutrition (PEM), diet reviews and daily protein intake (DPI). A simplified MDRD formula was employed to evaluate the level of estimated glomerular filtration rate (eGFR). According to the level of DPI, they were divided into 3 groups of very low protein diet (VLPD): DPI ≤ 0.6 g · kg(-1) · d(-1), low-protein diet (LPD): DPI >0.6-protein diet (NPD): DPI ≥ 0.8 · g · kg(-1) · d(-1). Among them, 4 cases (2.50%) progressed to uremia stage and received renal replacement therapy, 2(1.25%) experienced rapid decline in renal function, 9(5.66%) were hospitalized from cardio-cerebral diseases and the 2-year kidney survival rate was 97.5%. At the end of study, among 9 patients of PEM, 2 subjects had a serum level of albumin under 32 g/L and another 7 with a BMI 0.05). Within a certain range, differential protein intake may not significantly affect the prognosis of kidney for progressive CKD patients.

  17. Total proteins and protein fractions levels in pregnant rats subjected to whole-body gamma irradiation

    International Nuclear Information System (INIS)

    Mansour, M.A.; Roushdy, H.M.; Mazhar, F.M.; Abu-Gabal, H.A.

    1986-01-01

    A total number of 180 mature rats (120 females and 60 males) weighing from 120-140 g were used to study the effect of two doses (2 and 4 Gy) whole-body gamma irradiation on the level of total protein and protein fractions in serum of pregnant rats during the period of organogenesis. It was found that the levels of total protein, albumin and gamma globulins significantly decreased according to the doses of exposure. The levels of alpha and beta globulins significantly increased more in the serum of rats exposed to 2 Gy than in rats exposed to 4 Gy. The level of A/G ratio significantly decreased more in the serum of rats exposed to 2Gy than in those exposed to 4 Gy

  18. Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats.

    Science.gov (United States)

    Iwata, M; Shirayama, Y; Ishida, H; Kawahara, R

    2006-09-01

    Learned helplessness rats are thought to be an animal model of depression. To study the role of synapse plasticity in depression, we examined the effects of learned helplessness and antidepressant treatments on synapsin I (a marker of presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in the hippocampus by immunolabeling. (1) Learned helplessness rats showed significant increases in the expression of synapsin I two days after the attainment of learned helplessness, and significant decreases in the protein expression eight days after the achievement of learned helplessness. Subchronic treatment of naïve rats with imipramine or fluvoxamine significantly decreased the expression of synapsin I. (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training. Subchronic treatment of naïve rats with fluvoxamine but not imipramine showed a tendency to decrease the expression of synapsin I. (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness. Naïve rats subchronically treated with imipramine showed a tendency toward increased expression of MAP-2, but those treated with fluvoxamine did not. These results indicate that the neuroplasticity-related proteins synapsin I, GAP-43, and MAP-2 may play a role in the pathophysiology of depression and the mechanisms of antidepressants.

  19. Image quality dependence on thickness of sliced rat kidney taken by a simplest DEI construction

    International Nuclear Information System (INIS)

    Li Gang; Chen Zhihua; Wu Ziyu; Ando, M.; Pan Lin; Wang, J.Y.; Jiang, X.M.

    2005-01-01

    The excised rat kidney slices were investigated using a simplified diffraction-enhanced imaging (DEI) configuration with only two crystals: the first one working as monochromator and the second one working as analyzer in the Bragg geometry that was developed at Beijing Synchrotron Radiation Facility (BSRF). Many fine anatomic structures of the sliced rat kidneys with thickness of 2mm and 120μm can be distinguished clearly in the DEI images that were obtained at the shoulder of a rocking curve. The authors would like to emphasize that the thick and thin slices DEI provides very different images; in the thick sample only the structure with the big density gradient or that near the surface where X-ray comes out can be distinguished, while in the thin ones some fine structures, which can not be distinguished at the thick sample under the same condition, can be seen very clearly. The reason related with the counteraction of δ(x,y,z) gradient in the integral process along the X-ray path inside the thick sample is discussed

  20. Image quality dependence on thickness of sliced rat kidney taken by a simplest DEI construction

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang [Institute of High Energy Physics, Chinese Academy of Science, Yuquan Rd. No 19, Beijing 100039 (China)]. E-mail: lig@ihep.ac.cn; Chen Zhihua [China-Japan Friendship Institute of Clinical Medical Science, Yinghua Rd., Beijing 100029 (China); Wu Ziyu [Institute of High Energy Physics, Chinese Academy of Science, Yuquan Rd. No 19, Beijing 100039 (China); Ando, M. [Photon Factory, KEK, Oho 1-1, Tsukuba, Ibaraki 305-0801 (Japan); Pan Lin [China-Japan Friendship Institute of Clinical Medical Science, Yinghua Rd., Beijing 100029 (China); Wang, J.Y. [Institute of High Energy Physics, Chinese Academy of Science, Yuquan Rd. No 19, Beijing 100039 (China); Jiang, X.M. [Institute of High Energy Physics, Chinese Academy of Science, Yuquan Rd. No 19, Beijing 100039 (China)

    2005-08-11

    The excised rat kidney slices were investigated using a simplified diffraction-enhanced imaging (DEI) configuration with only two crystals: the first one working as monochromator and the second one working as analyzer in the Bragg geometry that was developed at Beijing Synchrotron Radiation Facility (BSRF). Many fine anatomic structures of the sliced rat kidneys with thickness of 2mm and 120{mu}m can be distinguished clearly in the DEI images that were obtained at the shoulder of a rocking curve. The authors would like to emphasize that the thick and thin slices DEI provides very different images; in the thick sample only the structure with the big density gradient or that near the surface where X-ray comes out can be distinguished, while in the thin ones some fine structures, which can not be distinguished at the thick sample under the same condition, can be seen very clearly. The reason related with the counteraction of {delta}(x,y,z) gradient in the integral process along the X-ray path inside the thick sample is discussed.

  1. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

    Directory of Open Access Journals (Sweden)

    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  2. Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease

    OpenAIRE

    Yokote, Shinya; Katsuoka, Yuichi; Yamada, Akifumi; Ohkido, Ichiro; Yokoo, Takashi

    2017-01-01

    Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced s...

  3. Dietary protein intake and chronic kidney disease.

    Science.gov (United States)

    Ko, Gang Jee; Obi, Yoshitsugu; Tortorici, Amanda R; Kalantar-Zadeh, Kamyar

    2017-01-01

    High-protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration. This can cause damage to glomerular structure leading to or aggravating chronic kidney disease (CKD). Hence, a low-protein diet (LPD) of 0.6-0.8 g/kg/day is often recommended for the management of CKD. We reviewed the effect of protein intake on incidence and progression of CKD and the role of LPD in the CKD management. Actual dietary protein consumption in CKD patients remains substantially higher than the recommendations for LPD. Notwithstanding the inconclusive results of the 'Modification of Diet in Renal Disease' (MDRD) study, the largest randomized controlled trial to examine protein restriction in CKD, several prior and subsequent studies and meta-analyses appear to support the role of LPD on retarding progression of CKD and delaying initiation of maintenance dialysis therapy. LPD can also be used to control metabolic derangements in CKD. Supplemented LPD with essential amino acids or their ketoanalogs may be used for incremental transition to dialysis especially on nondialysis days. The LPD management in lieu of dialysis therapy can reduce costs, enhance psychological adaptation, and preserve residual renal function upon transition to dialysis. Adherence and adequate protein and energy intake should be ensured to avoid protein-energy wasting. A balanced and individualized dietary approach based on LPD should be elaborated with periodic dietitian counseling and surveillance to optimize management of CKD, to assure adequate protein and energy intake, and to avoid or correct protein-energy wasting.

  4. Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats.

    Science.gov (United States)

    Xu, Xing-xin; Qi, Xiang-Ming; Zhang, Wei; Zhang, Chao-Qun; Wu, Xiao-Xu; Wu, Yong-Gui; Wang, Kun; Shen, Ji-Jia

    2014-05-15

    TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Protective Effect of Royal Jelly against Renal Damage in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Elham Ghanbari

    2015-03-01

    Full Text Available Background: Royal jelly has been shown to have antioxidant and antidiabetic effects. The objective of this study was to evaluate the protective effect of RJ against kidney damage in streptozotocin induced diabetic rats. Methods: Thirty two male Wistar rats were divided randomly into four groups (n=8 per group. Normal control and diabetic control groups received 1cc/day distilled water, normal RJ-treated and diabetic RJ-treated groups received 100mg RJ/kg body weight daily. Diabetes was induced by intraperitoneal injection of streptozotocin. At the end of the experiment, urine and kidney samples were collected for biochemical and histopathological analysis. Results: The results showed that diabetes could increase levels of urine urea, total protein and albumin significantly, and could decrease the levels of creatinine and uric acid in urine. In the kidney tissue homogenates, catalase activity and antioxidant power were significantly lower, whereas malondialdehyde levels were significantly higher in diabetic group when compared with control group. Diabetic rats showed severe histological changes in kidney tissues. Treatment of diabetic rats with RJ improved significantly all of these parameters. Conclusion: The present study revealed that treatment with RJ resulted in significant improvement in histopathological alterations in kidney tissue and urine parameters of diabetic rats. This could be due to its antioxidant activity and the ability of RJ for scavenging the free radicals released in diabetes. These findings suggest that RJ has protective effects on kidneys affected by diabetes mellitus.

  6. Effects of combined treatment of rats with cadmium and ionizing radiation on nucleic acids in the kidneys, liver and haemopoietic organs

    International Nuclear Information System (INIS)

    Slovinska, L.; Kropacova, K.; Kolesarova, M.; Misurova, E.

    2001-01-01

    The influence of Cd (1 mg/rat CdCl 2 i.p.) and/or gamma radiation (6 Gy) on RNA and DNA content and/or concentration in the intact kidney and hypertrophic kidney (on the 44th hour after unilateral nephrectomy - UN) and in other slowly and quickly proliferating organs was studied. The period between administration of Cd and ionizing irradiation (Ir) in the group with combined treatment was 30 min, between treatment (administration of Cd, Ir and combination of both treatments - Cd + Ir) and UN it was 1, 7, 14 and 21 days. The total extent of damage caused by the treatments in the investigated organs was following: intact kidney < liver < hypertrophic kidney and bone marrow < spleen < thymus. In the intact and hypertrophic kidney and liver, the administration of Cd caused more extensive changes in comparison with gamma irradiation and the effects of combination of the treatments were similar to those of Cd alone. In the bone marrow, spleen and thymus, more profound changes were observed after Ir in comparison with Cd administration, and the effects of combined treatment were similar to the effects of Ir alone. The changes in the hypertrophic kidney after administration of Cd and/or Ir were more extensive than in the intact kidney, which suggests latent injury induction in the rat kidney by these noxa. The higher effectiveness of the treatments in the hypertrophic kidney than in the intact one was manifested mostly by the decrease in the RNA and DNA content, which was mainly due to inhibition of growth induced by UN and not by a real decrease in DNA and RNA contents caused by loss of damaged cells. (author)

  7. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun Oularbi

    2014-04-01

    Full Text Available Lambda-cyhalothrin (LCT is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administered orally over 28 days. The effects of the insecticide on various biochemical parameters were evaluated at 14 and 28 days. Histopathological studies were carried out in the kidneys and adrenal glands at the end of the experiment. Lambda-cyhalothrin, as a pyrethroid insecticide, induced significant increases (P≤0.05 in plasma urea, creatinine, uric acid and glucose concentrations, and alanine aminotransferase and aspartate aminotransferase activities after 14 and 28 days. In the rat plasma samples after 28 days, residual concentrations of LCT 1R, cis,

  8. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

    Science.gov (United States)

    Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

    2017-01-01

    Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

  9. The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

    Science.gov (United States)

    Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

    2018-04-11

    Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

  10. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    Background: Cardiovascular disease is the major cause of hospitalization and mortality in chronic kidney disease (CKD). C- reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. CKD patients with elevated CRP should be identified early with institution of measures to treat ...

  11. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    2016-03-01

    Mar 1, 2016 ... SUMMARY. Background: Cardiovascular disease is the major cause of hospitalization and mortality in chronic kidney disease. (CKD). C-reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. CKD patients with elevated CRP should be identified early with ...

  12. Serum C-reactive protein levels in pre-dialysis chronic kidney ...

    African Journals Online (AJOL)

    2016-03-01

    Mar 1, 2016 ... 1Department of Internal Medicine, Kidney Care Centre, Ondo, Ondo State, Nigeria. ... C-reactive protein (CRP) is a marker of cardiovascular disease and predictor of mortality in CKD patients. ... Methods: This was a case-control study involving 80 consecutive CKD patients and 40 control subjects without.

  13. In vivo tracking of magnetically labeled mesenchmal stem cells injected via renal arteries in kidney failure rat

    International Nuclear Information System (INIS)

    Sun Junhui; Teng Gaojun; Ju Shenghong; Ma Zhanlong; Mai Xiaoli; Zhang Yu; Ma Ming

    2006-01-01

    Objective: To evaluate in vivo depiction and tracking for magnetically labeled bone marrow mesenchymal stern cells (MSCs) in a renal failure rat model injected intravascularly using a 1.5 T magnetic resonance imaging (MRI) system. Methods: Rat MSCs were isolated, purified, expanded and then incubated with home synthesized Fe 2 O 3 -PLL. Prussian blue stain was employed for identifying intracellular irons. An acute renal failure in rat was induced by intramuscular injection of glycerol and MSCs were injected into renal arteries of 11 recipients (labeled cells in six, unlabeled cells in five). MR images of kidneys were obtained respectively before injection of MSCs, and immediately, 1, 3, 5, and 8 clays after transplantation. MR imaging findings were analyzed, which were correlated with histological findings. Results: Rat MSCs were successfully labeled, and labeling efficiency was almost 100%. Prussian blue staining of Fe 2 O 3 -PLL labeled cells revealed the presence of iron-containing vesicles or endosomes in the cytoplasm. In the renal failure model of rats, the labeled MSCs were demonstrated as signal intensity loss in renal cortex on T 2 * -weighted MR images. The signal intensity decrease was visualized up to days 8 after transplantation. Histological analyses showed that most Prussian blue staining-positive cells were well correlated with the area where a signal intensity loss was observed in MRI. Signal intensity decrease was not detected after transplantation of unlabeled cells. Conclusion: The rat MSCs can be effectively labeled with Fe 2 O 3 -PLL. 1.5-T MR imaging seems to be a good technique to monitor the magnetically labeled MSCs in vivo in renal failure rat model intravascularly administered, which may have much more potential values for studying the engraftment of stem cells in kidneys. (authors)

  14. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Nelli Giribabu

    2014-01-01

    Full Text Available P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO product, malondialdehyde (MDA, and the diminution of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.

  15. NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

    Science.gov (United States)

    Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

    2008-01-01

    The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

  16. Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

    Science.gov (United States)

    Geng, Xiao-Dong; Zheng, Wei; Wu, Cong-Mei; Wang, Shu-Qiang; Hong, Quan; Cai, Guang-Yan; Chen, Xiang-Mei; Wu, Di

    2016-01-01

    Background: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD. Methods: Adult male Sprague–Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining. Results: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs. Conclusions: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury. PMID:26879011

  17. Effect of dietary protein quality and feeding level on milk secretion and mammary protein synthesis in the rat

    International Nuclear Information System (INIS)

    Sampson, D.A.; Jansen, G.R.

    1985-01-01

    Protein synthesis was studied in mammary tissue of rats fed diets deficient in protein quality and/or restricted in food intake throughout gestation and lactation. Diets containing 25% wheat gluten (WG), wheat gluten plus lysine and threonine (WGLT), or casein (C) were pair-fed from conception until day 15 of lactation at 100% or 85% of WG ad libitum consumption (PF100 and PF85, respectively). A seventh group was fed C ad libitum. Rates of protein synthesis were measured in vivo at day 15 of lactation from incorporation of [3- 3 H]phenylalanine. At both PF100 and PF85, fractional and absolute rates of mammary gland protein synthesis were two- to three-fold higher in rats fed C than in those fed WG. Pup weights showed similar treatment effects. Both mammary protein synthesis rates and pup weights were significantly higher in rats fed C at PF85 than rats fed WG ad libitum. Food restriction from PF100 to PF85 depressed pup weights and mammary protein synthesis rates in rats fed WGLT, but had no effect in rats fed WG. These results demonstrate that when food intake is restricted, improvement of protein quality of the maternal diet increases milk output in the rat in association with increased rates of mammary protein synthesis

  18. P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Directory of Open Access Journals (Sweden)

    Adelson M Rodrigues

    Full Text Available Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v. and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L. By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3'-O-(4-benzoylbenzoyl adenosine5'-triphosphate (specific agonist and adenosine triphosphate (nonspecific agonist (all p<0.05. All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy in DM groups. Lipoperoxidation was strongly correlated with P2X(7 receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7 receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  19. P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cassia T; Fernandes, Maria Jose S; Paredes-Gamero, Edgar J; Buri, Marcus V; Curi, Marcus V; Ferreira, Alice T; Araujo, Sergio R R; Punaro, Giovana R; Maciel, Fabiane R; Nogueira, Guilherme B; Higa, Elisa M S

    2014-01-01

    Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  20. On the presence of prostatic secretion protein in rat seminal fluid

    International Nuclear Information System (INIS)

    Borgstroem, E.; Pousette, A.; Bjoerk, P.; Hoegberg, B.; Carlstroem, K.; Sundelin, B.; Gustafsson, J.A.

    1981-01-01

    The copulating plug collected from the tip of the penis from rats immediately after decapitation contains a protein very similar and probably identical to PSP (prostatic secretion protein); this protein has earlier been purified from rat prostatic cytosol and characterized. The protein present in the copulating plug interacts with [3H]estramustine and binds to the antibody raised against rat PSP. The concentration of the protein in the copulating plug is 400 ng/mg of total protein, when measured using the radioimmunoassay technique developed earlier for measurement of PSP in rat prostate. The [3H]estramustine-protein complex formed in a preparation of the copulating plug has an apparent molecular weight of about 50,000 and a sedimentation coefficient of about 3S when analyzed using sucrose density gradient centrifugation. The complex was retained on Concanavalin-A Sepharose indicating that the protein is a glycoprotein. Binding of the complex was also observed on hydroxylapatite and DEAE-Sephadex columns, from which it was eluted at 0.18 M KCl. Light microscope autoradiograms of rat sperms incubated with 125I-labeled PSP indicated that PSP is bound to all parts of the sperms. A macromolecule interacting with the PSP-antibodies is also present in human seminal fluid but at a concentration considerably lower than in rat seminal fluid. The present study shows that a macromolecule probably identical to prostatic secretion protein is present in the copulating plug from the rat. The biological role of this protein in normal male fertility is discussed

  1. Effect of Fenugreek (Trigonella Foenum-Graecum) Supplementation on Radiation-Induced Oxidative Stress in Liver and Kidney of Rats

    Energy Technology Data Exchange (ETDEWEB)

    EI-Tawil, G A [Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2009-07-01

    Whole body exposure to ionizing radiation provokes oxidative damage, organ dysfunction and metabolic disturbances. Fenugreek (Trigonella foenumgraecum L. Leguminosae), one of the oldest medicinal plants rich in polyphenolic compounds is known to possess antioxidant properties. The present study was designed to determine the possible protective effect of fenugreek, against {gamma}-radiation-induced oxidative stress in liver and kidney tissues of rats. In parallel, the alteration in the activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as markers of liver function, creatinine and urea levels as markers of kidney function. In addition, serum glucose and insulin levels were determined as markers for carbohydrate metabolism. Irradiated rats were whole body exposed to 3.5 Gy (Acute dose) {gamma}-radiations. Fenugreek-treated irradiated rats received 1g fenugreek seed powder/kg body weight/day, by gavages, during 7 days before irradiation. Animals were sacrificed on the 1 sl day after irradiation. The results obtained demonstrated that exposure to ionizing radiation induced significant decreases in SOD and CAT activities and GSH content associated to significant increase of TBARS levels in liver and kidney. Fenugreek treatment has significantly attenuated radiation-induced oxidative stress in both tissues, which was substantiated by the significant amelioration of serum ALP, AST and ALT activities, creatinine, urea, glucose, and insulin levels. It could be concluded that fenugreek would protect from oxidative damage and metabolic disturbances induced by ionizing irradiation.

  2. Effect of Fenugreek (Trigonella Foenum-Graecum) Supplementation on Radiation-Induced Oxidative Stress in Liver and Kidney of Rats

    International Nuclear Information System (INIS)

    EI-Tawil, G.A.

    2009-01-01

    Whole body exposure to ionizing radiation provokes oxidative damage, organ dysfunction and metabolic disturbances. Fenugreek (Trigonella foenumgraecum L. Leguminosae), one of the oldest medicinal plants rich in polyphenolic compounds is known to possess antioxidant properties. The present study was designed to determine the possible protective effect of fenugreek, against γ-radiation-induced oxidative stress in liver and kidney tissues of rats. In parallel, the alteration in the activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as markers of liver function, creatinine and urea levels as markers of kidney function. In addition, serum glucose and insulin levels were determined as markers for carbohydrate metabolism. Irradiated rats were whole body exposed to 3.5 Gy (Acute dose) γ-radiations. Fenugreek-treated irradiated rats received 1g fenugreek seed powder/kg body weight/day, by gavages, during 7 days before irradiation. Animals were sacrificed on the 1 sl day after irradiation. The results obtained demonstrated that exposure to ionizing radiation induced significant decreases in SOD and CAT activities and GSH content associated to significant increase of TBARS levels in liver and kidney. Fenugreek treatment has significantly attenuated radiation-induced oxidative stress in both tissues, which was substantiated by the significant amelioration of serum ALP, AST and ALT activities, creatinine, urea, glucose, and insulin levels. It could be concluded that fenugreek would protect from oxidative damage and metabolic disturbances induced by ionizing irradiation

  3. Effects of cyanide on selenium metabolism in rats

    International Nuclear Information System (INIS)

    Beilstein, M.A.; Whanger, P.D.

    1984-01-01

    Adult male rats were given drinking water containing either 0 or 150 ppm cyanide for 2 weeks. They were then injected with 5 microCi 75 Se-selenite, and excretion of radioactivity in urine and feces was determined. No difference in excretion of 75 Se occurred during the rapid phase, but the cyanide-treated rats (T1/2 28 days) excreted significantly more 75 Se in urine than control (T1/2 38 days) rats. Cyanide had no effect on excretion of 75 Se in feces or on the distribution of 75 Se in cytosolic proteins in liver, kidney, muscle or testes. In a second experiment weanling male rats were given water with either 0 or 150 ppm cyanide and were killed for glutathione peroxidase assay and selenium analysis in blood, kidney, liver, muscle and testes after 3, 6 or 9 weeks of treatment. Glutathione peroxidase activity and selenium concentrations were significantly reduced by cyanide in all tissues except testes

  4. Health effects of an increased protein intake on kidney function and colorectal cancer risk factors, including the role of animal and plant protein sources – the PREVIEW project

    DEFF Research Database (Denmark)

    Møller, Grith

    intake, including the role of animal and plant protein in pre-diabetic, overweight or obese individuals on health outcomes: markers of kidney function and putative risk factors for colorectal cancer as well as insulin sensitivity and kidney function in healthy individuals. The thesis is based on PREVIEW......, especially plant protein, on insulin sensitivity and kidney function. In paper II, the aim of the study was to assess the effect after one year of a higher protein intake on kidney function, measured by in creatinine clearance. This was investigated in pre-diabetic older adults based on a sub-group of 310...... pre-diabetic individuals included in the PREVIEW RCT. We found that a higher protein intake was associated with a significant increase in urea to creatinine ratio and serum urea after one year. There were no associations between increased protein intake and creatinine clearance, estimated glomerular...

  5. Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K. [Heidelberg Univ., Mannheim (Germany). Dept. of Medicine V

    2017-05-01

    To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

  6. Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

    International Nuclear Information System (INIS)

    Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G.; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K.

    2017-01-01

    To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

  7. Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

    Science.gov (United States)

    Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

    1985-01-01

    On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

  8. Phosphorus-31 NMR magnetization transfer measurements of metabolic reaction rates in the rat heart and kidney in vivo

    International Nuclear Information System (INIS)

    Koretsky, A.P.

    1984-01-01

    31 P NMR is a unique tool to study bioenergetics in living cells. The application of magnetization transfer techniques to the measurement of steady-state enzyme reaction rates provides a new approach to understanding the regulation of high energy phosphate metabolism. This dissertation is concerned with the measurement of the rates of ATP synthesis in the rat kidney and of the creatine kinase catalyzed reaction in the rat heart in situ. The theoretical considerations of applying magnetization transfer techniques to intact organs are discussed with emphasis on the problems associated with multiple exchange reactions and compartmentation of reactants. Experimental measurements of the ATP synthesis rate were compared to whole kidney oxygen consumption and Na + reabsorption rates to derive ATP/O values. The problems associated with ATP synthesis rate measurements in kidney, e.g. the heterogeneity of the inorganic phosphate resonance, are discussed and experiments to overcome these problems proposed. In heart, the forward rate through creatine kinase was measured to be larger than the reverse rate. To account for the difference in forward and reverse rates a model is proposed based on the compartmentation of a small pool of ATP

  9. Effect of turmeric and its active principle curcumin on t(3)-induced oxidative stress and hyperplasia in rat kidney: a comparison.

    Science.gov (United States)

    Samanta, Luna; Panigrahi, Jogamaya; Bhanja, Shravani; Chainy, Gagan B N

    2010-10-01

    The present study was designed to compare the potential of turmeric and its active principle curcumin on T(3)-induced oxidative stress and hyperplasia. Adult male Wistar strain rats were rendered hyperthyroid by T(3) treatment (10 μg · 100 g(-1) · day(-1) intraperitoneal for 15 days in 0.1 mM NaOH) to induce renal hyperplasia. Another two groups were treated similarly with T(3) along with either turmeric or curcumin (30 mg kg(-1) body weight day(-1) orally for 15 days). The results indicate that T(3) induces both hypertrophy and hyperplasia in rat kidney as evidenced by increase in cell number per unit area, increased protein content, tubular dilation and interstitial edema. These changes were accompanied by increased mitochondrial lipid peroxidation and superoxide dismutase activity without any change in catalase activity and glutathione content suggesting an oxidative predominance. Both turmeric and curcumin were able to restore the level of mitochondrial lipid peroxidation and superoxide dismutase activity in the present dose schedule. T(3)-induced histo-pathological changes were restored with turmeric treatment whereas curcumin administration caused hypoplasia. This may be due to lower concentration of curcumin in the whole turmeric. Thus it is hypothesized that regulation of cell cycle in rat kidney by T(3) is via reactive oxygen species and curcumin reveres the changes by scavenging them. Although the response trends are comparable for both turmeric and curcumin, the magnitude of alteration is more in the later. Turmeric in the current dose schedule is a safer bet than curcumin in normalizing the T(3)-induced hyperplasia may be due to the lower concentration of the active principle in the whole spice.

  10. Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    César Tadeu Spadella

    1997-03-01

    Full Text Available We studied the effects of islet of Langerhans transplantation (IT on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC, group GIT included 15 alloxan-induced diabetic rats (DC, and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT. Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT, mesangial enlargement (ME, and Bowman's capsule thickening (BCT in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01. However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE and tubular lumen protein (PRO observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation.

  11. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Md. Abdul Hye Khan

    2014-09-01

    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  12. Biological responses to perfluorododecanoic acid exposure in rat kidneys as determined by integrated proteomic and metabonomic studies.

    Directory of Open Access Journals (Sweden)

    Hongxia Zhang

    Full Text Available BACKGROUND: Perfluorododecanoic acid (PFDoA is a perfluorinated carboxylic chemical (PFC that has broad applications and distribution in the environment. While many studies have focused on hepatotoxicity, immunotoxicity, and reproductive toxicity of PFCAs, few have investigated renal toxicity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used comparative proteomic and metabonomic technologies to provide a global perspective on renal response to PFDoA. Male rats were exposed to 0, 0.05, 0.2, and 0.5 mg/kg/day of PFDoA for 110 days. After 2-D DIGE and MALDI TOF/TOF analysis, 79 differentially expressed proteins between the control and the PFDoA treated rats (0.2 and 0.5 mg-dosed groups were successfully identified. These proteins were mainly involved in amino acid metabolism, the tricarboxylic acid cycle, gluconeogenesis, glycolysis, electron transport, and stress response. Nuclear magnetic resonance-based metabonomic analysis showed an increase in pyruvate, lactate, acetate, choline, and a variety of amino acids in the highest dose group. Furthermore, the profiles of free amino acids in the PFDoA treated groups were investigated quantitatively by high-coverage quantitative iTRAQ-LC MS/MS, which showed levels of sarcosine, asparagine, histidine, 1-methylhistidine, Ile, Leu, Val, Trp, Tyr, Phe, Cys, and Met increased markedly in the 0.5 mg dosed group, while homocitrulline, α-aminoadipic acid, β-alanine, and cystathionine decreased. CONCLUSION/SIGNIFICANCE: These observations provide evidence that disorders in glucose and amino acid metabolism may contribute to PFDoA nephrotoxicity. Additionally, α(2u globulin may play an important role in protecting the kidneys from PFDoA toxicity.

  13. Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues.

    Science.gov (United States)

    Lollo, Pablo C B; Moura, Carolina S; Morato, Priscila N; Amaya-Farfan, Jaime

    2013-01-01

    Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP), but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric) and downhill (predominantly eccentric) muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7%) and downhill (-7% of inclination). At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK) and lactate dehydrogenase (LDH) were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal). When the contraction was concentric (uphill) and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL(-1)) in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively). The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus. Key PointsExercise can induce increases in HSP70 in

  14. Dietary Protein Intake and Chronic Kidney Disease

    Science.gov (United States)

    Ko, Gang Jee; Obi, Yoshitsugu; Tortoricci, Amanda R.; Kalantar-Zadeh, Kamyar

    2018-01-01

    Purpose of review High protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration. This can cause damage to glomerular structure leading to or aggravating chronic kidney disease (CKD). Hence, a low protein diet (LPD) of 0.6–0.8 g/kg/day is often recommended for the management of CKD. We reviewed the effect of protein intake on incidence and progression of CKD and the role of LPD the CKD management. Recent findings Actual dietary protein consumption in CKD patients remain substantially higher than the recommendations for LPD. Notwithstanding the inconclusive results of the Modification of Diet in Renal Disease (MDRD) study, the largest randomized controlled trial to examine protein restriction in CKD, several prior and subsequent studies and meta-analyses including secondary analyses of the MDRD data appear to support the role of LPD on retarding progression of CKD and delaying initiation of maintenance dialysis therapy. LPD can also be used to control metabolic derangements in CKD. Supplemented LPD with essential amino acids or their keto-analogs may be used for incremental transition to dialysis especially in non-dialysis days. An LPD management in lieu of dialysis therapy can reduce costs, enhance psychological adaptation, and preserve residual renal function upon transition to dialysis. Adherence and adequate protein and energy intake should be ensured to avoid protein-energy wasting. Summary A balanced and individualized dietary approach based on LPD should be elaborated with periodic dietitian counselling and surveillance to optimize management of CKD, to assure adequate protein and energy intake and to avoid or correct protein-energy wasting. PMID:27801685

  15. Binding and functional effects of atrial natriuretic factor in isolated rat kidney

    International Nuclear Information System (INIS)

    Suzuki, M.; Almeida, F.A.; Nussenzveig, D.R.; Sawyer, D.; Maack, T.

    1987-01-01

    A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with 125 I-labeled and unlabeled ANF 1-28 to determine the following: (1) distribution, capacity (C max ), and apparent affinity (S 50 ) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and (2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had >90% of total binding sites whereas papilla had <2% of total binding sites with a 10-fold lower apparent affinity than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrates that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone

  16. Higher protein intake is not associated with decreased kidney function in pre-diabetic older adults following a one-year intervention

    DEFF Research Database (Denmark)

    Møller, Grith; Andersen, Jens Rikardt; Ritz, Christian

    2018-01-01

    Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic...... intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults....

  17. Anionic and cationic drug secretion in the isolated perfused rat kidney after neonatal surgical induction of ureteric obstruction.

    NARCIS (Netherlands)

    Gier, R.P.E. de; Feitz, W.F.J.; Masereeuw, R.; Wouterse, A.C.; Smits, D.; Russel, F.G.M.

    2003-01-01

    OBJECTIVE: To study the pathophysiological changes of renal tubular drug transport mechanisms in congenital renal obstruction, by developing a model for perfusing the isolated kidney (IPK) after neonatal surgical induction of partial ureteric obstruction in Hanover Wistar rats. MATERIAL AND METHODS:

  18. Thiazide diuretic receptors: Autoradiographic localization in rat kidney with [3H]metolazone

    International Nuclear Information System (INIS)

    Beaumont, K.; Vaughn, D.A.; Healy, D.P.

    1989-01-01

    The localization of binding sites for [ 3 H]metolazone, a quinazolinesulfonamide diuretic with thiazide-like actions, was determined by in vitro autoradiography. [ 3 H]Metolazone bound saturably to rat kidney sections incubated in vitro with a dissociation constant (Kd) = 3.4 nM and binding site density = 0.14 pmol/mg of protein. Incubation conditions were used that excluded binding to low affinity sites and carbonic anhydrase. Pharmacological specificity of binding was consistent with labeling of physiologically relevant thiazide diuretic receptors, as identified in previous studies of [ 3 H]metolazone binding to renal membranes. Autoradiographs obtained with tritium-sensitive film demonstrated that binding sites were limited to the renal cortex and were relatively sparsely distributed. Higher resolution autoradiography indicated that [ 3 H] metolazone binding sites were localized in a highly specific manner over short lengths of tubular segments, which by their morphology and distribution most likely represented distal convoluted tubules. In the short sections of tubule that contained receptors, labeling was very dense and appeared to be more prevalent over luminal than peritubular surfaces. The intrarenal distribution of [ 3 H]metolazone binding sites provides further evidence for their identity as thiazide diuretic receptors. These results are consistent with physiological studies demonstrating that the early distal tubule is the location of thiazide-sensitive sodium chloride cotransport

  19. Comparative proteomic analysis of differentially expressed proteins in the urine of reservoir hosts of leptospirosis.

    Directory of Open Access Journals (Sweden)

    Jarlath E Nally

    Full Text Available Rattus norvegicus is a natural reservoir host for pathogenic species of Leptospira. Experimentally infected rats remain clinically normal, yet persistently excrete large numbers of leptospires from colonized renal tubules via urine, despite a specific host immune response. Whilst persistent renal colonization and shedding is facilitated in part by differential antigen expression by leptospires to evade host immune responses, there is limited understanding of kidney and urinary proteins expressed by the host that facilitates such biological equilibrium. Urine pellets were collected from experimentally infected rats shedding leptospires and compared to urine from non-infected controls spiked with in vitro cultivated leptospires for analysis by 2-D DIGE. Differentially expressed host proteins include membrane metallo endopeptidase, napsin A aspartic peptidase, vacuolar H+ATPase, kidney aminopeptidase and immunoglobulin G and A. Loa22, a virulence factor of Leptospira, as well as the GroEL, were increased in leptospires excreted in urine compared to in vitro cultivated leptospires. Urinary IgG from infected rats was specific for leptospires. Results confirm differential protein expression by both host and pathogen during chronic disease and include markers of kidney function and immunoglobulin which are potential biomarkers of infection.

  20. The ameliorative effect of grape seed extract(GSE) on sodium borate-inducing kidney injury of male albino rats

    International Nuclear Information System (INIS)

    Ayad, S.K.Y.

    2013-01-01

    Borax (sod-borate) is a toxic compound that is implicated daily to environmental pollutant, so occupational exposure leading to adverse effects on functions of some organs causing their damage as nephrotoxicity, neurotoxicity, hepatotoxicity and testicular atrophy . In particularly, kidney is the most organ that is affected by borax exposure due to continuous exposure with slow rate of excretion leading to accumulation in the renal tissue. Supplementation with high potent antioxidant grape seed extract may alleviate the worse damage effects induced in the kidney as a result of continual exposure of borax in our daily life. The current study aimed to evaluate the ameliorative effect of grape seed extract on renal injury of male albino rats intoxicated with sod-borate. Twenty eight male albino rats were classified to 4 groups(GI and II and III and IV).GI served as a control, group GII was a group intoxicated with sod-borate for 45 days, where as rats in GIII supplemented with GSE beside sod-borate for 45 days , GIV was a group supplemented with GSE only. Serum and kidney samples were collected for biochemical, histopathological and DNA examinations. Significant elevation in the levels of blood urea and creatinine in GII were observed when compared to control group(GI). Significant decline were prominent in biochemical kidney functions when intoxicated group supplemented with GSE(GIII) , where as non significant changes were observed between control group and group supplemented with GSE only (GIV). Significant increase in both cytokines TNF-α and IL-6 was observed in group intoxicated with sod-borate(GII) when compared to control rats(GI). Oral supplementation with high potent antioxidant GSE (GIII) caused alleviation in the kidney injury leading to the reduction of both pro-inflammatory mediator cytokines TNF-α and IL-6. DNA% fragment migration showed that worse significant migration of DNA fragements were observed in toxicated group(GII) followed by increase in

  1. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

    Science.gov (United States)

    Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

  2. Dopaminergic Immunofluorescence Studies in Kidney Tissue.

    Science.gov (United States)

    Gildea, J J; Van Sciver, R E; McGrath, H E; Kemp, B A; Jose, P A; Carey, R M; Felder, R A

    2017-01-01

    The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.

  3. Molecular events in matrix protein metabolism in the aging kidney

    Science.gov (United States)

    Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Choudhury, Goutam G.; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.

    2018-01-01

    Summary We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFβ mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFβ-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Agephase-specific regulation of matrix protein synthesis occurs and involves matrix protein-specific transcriptional and post-transcriptional mechanisms. PMID:23020145

  4. The role of vascular protein and renin in chronic two-kidney, one clip Goldblatt hypertension

    International Nuclear Information System (INIS)

    Nakada, T.; Yamori, Y.

    1982-01-01

    Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact. Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). 3 H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of 3 H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment. Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of 3 H-proline into non-collagenous protein and collagen of testicular or mesenteric artery. These results indicate that increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogenesis of chronic hypertension in 2K-1C rats, and renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension

  5. D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2013-02-15

    Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative stress

  6. Biochemical studies on gamma irradiated male rats fed on whey protein concentrate

    International Nuclear Information System (INIS)

    Mohamed, N.E; Anwar, M.M.; El-bostany, N.A.

    2010-01-01

    This study carried out to investigate the possible role of whey protein protein concentrate in ameliorating some biochemical disorders induced in gamma irradiated male rats. Forty eight male albino rats were divided into four equal groups: Group 1 fed on normal diet during experimental period. Group 2 where the diet contain 15 % whey protein concentrate instead of soybean protein . Group 3 rats were exposed to whole body gamma radiation with single dose of 5 Gy and fed on the normal diet. Group 4 rate exposed to 5 Gy then fed on diet contain 15 % whey protein concentrate, the rats were decapitated after two and four weeks post irradiation. Exposure to whole body irradiation caused significant elevation of serum ALT, AST, glucose, urea, creatinine and total triiodothyronine with significant decrease in total protein, albumin and thyroxin. Irradiated rats fed on whey protein concentrate revealed significant improvement of some biochemical parameters. It could be conclude that whey protein concentrate may be considered as a useful protein source for reducing radiation injury via metabolic pathway.

  7. Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

    Science.gov (United States)

    Huang, Zhongdi; He, Liqun; Huang, Di; Lei, Shi; Gao, Jiandong

    2015-10-21

    Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

  8. MiR-139-3p is related to left ventricular hypertrophy and cardiomyocyte apoptosis in two-kidney one-clip hypertensive rats

    Directory of Open Access Journals (Sweden)

    Yang Xiaomin

    2015-01-01

    Full Text Available MicroRNAs (miRNAs are important post-transcriptional regulators of gene expression in many physiological and pathological processes. Previous studies have reported the role of miR-139-3p in cancer. However, its specific roles and functions in the heart undergoing hypertrophy have yet to be fully elucidated. In the present study, a significant upregulation of miR-139-3p expression was demonstrated in the left ventricular myocardium of two-kidney one-clip (2K1C hypertensive rats using microarray and quantitative real-time PCR (qRT-PCR. Based on computational analysis, we observed that miR-139-3p can control the expression of mitogen-activated protein kinase 1 (MAPK1 as a target gene, which is essential for the induction of cardiac hypertrophy and cardiomyocyte apoptosis. This study provides first information that the highly expressed miR-139-3p might be closely involved in MAPK1-mediated cardiac hypertrophy and cardiomyocyte apoptotic processes in 2K1C rat.

  9. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

    Science.gov (United States)

    Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

    2014-11-01

    This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

  10. Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer.

    Science.gov (United States)

    Si, Tong; Yang, Guosheng; Qiu, Xiaofu; Luo, Youhua; Liu, Baichuan; Wang, Bingwei

    2015-01-01

    To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients' prognosis was evaluated in kidney cancer. IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (Pkidney cancer and correlates with patients prognosis, which may be served as a potential marker for the diagnosis and treatment of kidney cancer.

  11. 15-hydroxyprostaglandin dehydrogenase activity in vitro in lung and kidney of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Toft, B.S.

    1978-01-01

    Weanling rats were fed for 6 months on a diet deficient in essential fatty acids: either fat-free, or with 28% (w/w) partially hydrogenated fish oil. Control rats were fed a diet with 28% (w/w) arachis oil for 6 months. 15-Hydroxyprostaglandin dehydrogenase activity was determined as initial rates...... of the two groups on diets deficient in essential fatty acids as compared to the control group. No difference was observed in dehydrogenase activity in the kidneys. The dehydrogenase may be of importance for the regulation of the level of endogenous prostaglandins and, thus, a decrease in activity could...

  12. Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

    Science.gov (United States)

    Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

    2017-11-01

    To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

  13. Immunotoxicological studies of genetically modified rice expressing PHA-E lectin or Bt toxin in Wistar rats

    DEFF Research Database (Denmark)

    Kroghsbo, Stine; Madsen, Charlotte Bernhard; Poulsen, Morten

    2008-01-01

    As part of the SAFOTEST project the immunmodulating effect of Cry1Ab protein from Bacillus thuringiensis (Bt) and PHA-E lectin from kidney bean (Phaseolus vulgaris erythroagglutinin) was examined in 28- and 90-day feeding studies in Wistar rats. PHA-E lectin was chosen as positive control. Rats...

  14. Autoradiographic changes in the kidney of the whole-body sublethally x-ray irradiated rat

    Energy Technology Data Exchange (ETDEWEB)

    Olinic, A; Uray, Z

    1977-01-01

    203Hg-hydroxymersalyl uptake/gram of kidney (HU), renal autoradiographic and histologic aspect after 800 R x-ray whole-body rat irradiation was studied. Twenty-four to seventy-two hours after irradiation, HU increased, while tubular autoradiographic granularity decreased. Their return to the control levels occurred gradually within two weeks. The relations of these findings to the early circulatory and dystrophic changes, as well as to the subsequent postirradiation restoring renal process are discussed.

  15. Investigations of nephrotoxicity caused by ionic and non-ionic contrast media in rats with previously damaged and not previously damaged kidneys and special view to urinary enzyme determinations

    International Nuclear Information System (INIS)

    Hofmeister, R.

    1988-01-01

    In this study ionic (meglumine amidotrizoate) and non-ionic contrast media (SHH 340 AB, Iohexol, Iopromide, Iosimide and Iopamidol) were tested for their nephrotoxicity in rats. During the experiment detections of urea nitrogen, serum creatinine and urinary enzymes as well as histological examinations of the kidneys were carried out for the diagnosis of acute renal damage. The results obtained in this study demonstrate that rats are not very sensitive to non-ionic contrast media with regard to kidney damage and determinations of urinary enzymes are valuable for the diagnosis of contrast media induced acute kidney damage in living animals. (orig./MG) [de

  16. Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

    Science.gov (United States)

    Maji, Uttam Kumar; Jana, Pradipta; Chatterjee, Mitali; Karmakar, Sanmay; Saha, Arup; Ghosh, Tamal Kanti

    2018-03-01

    Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.

  17. Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and Histopathology in Kidney of Wistar Rat.

    Science.gov (United States)

    Suliman Al-Gebaly, Asma

    2017-01-01

    Cadmium (Cd) is a non-essential metal whose dispersion in the environment has increased recently, Cd may enhance cell oxidative stress that leads to DNA damage and apoptotic cell death. The study aimed to evaluate the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced oxidative stress and histopathology of the kidney of Wistar rats. Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1) for five weeks with two groups pre-treated with 'Arctium lappa' administration, 100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test to determine the difference among means using the JMP version 12. Results revealed that cadmium induced a significant disorganization (pArctium lappa kg-1 b.wt., showed a slightly less hypercellularity of glomerulus and reduction in the cell tail (59 μm). Furthermore, histological sections of kidney of rats pre-treated with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules and glomerulus with a prominent urinary space beside tail length of cells was recorded as 39 μm which was lower in comparison to other groups. Moreover, cadmium induced cellular destruction of the kidney was resumed with the pre-treatment of the secondary metabolites as an antioxidant compounds that produced from plant extracts. Arctium lappa leaf extract was efficient at both applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative effect.

  18. Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats.

    Science.gov (United States)

    Zhang, Yue-Yue; Huang, Juan; Yang, Man; Gu, Li-Jie; Ji, Jia-Yao; Wang, Li-Jun; Yuan, Wei-Jie

    2015-09-14

    Ketoacids (KA) are known to preserve muscle mass among patients with chronic kidney disease (CKD) on a low-protein diet (LPD). The present study was to compare the effects of KA supplemented diet therapy in autophagy and inflammation in CKD rats' skeletal muscle. Rats with 5/6 nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day protein [normal-protein diet (NPD)], 3 g/kg/day protein (LPD) or 3 g/kg/day protein which including 5% protein plus 1% KA (LPD + KA) for 24 weeks. Sham-operated rats with NPD intake were used as control. LPD could improve body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (microtubule-associated protein 1 light chain 3), p62, Parkin and PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total mtDNA (mitochondiral DNA) and cytosol mtDNA, NACHT-PYD-containing protein 3 (NALP3) inflammasome than LPD group, but its reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1β (interleukin-1-beta) was lower in LPD and LPD + KA group than the NPD group, but IL-18 showed no significant difference among control and CKD group; toll-like receptor signalling-dependent IL-6 was higher in LPD + KA group than LPD group, but tumor necrosis factor-α (TNF-α) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating inflammation to provide new therapeutic approaches for CKD protein energy wasting (PEW). © 2015 Authors.

  19. Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats.

    Science.gov (United States)

    Lakshmi, G Dhana; Kumar, P Ravi; Bharavi, K; Annapurna, P; Rajendar, B; Patel, Pankaj T; Kumar, C S V Satish; Rao, G S

    2012-02-01

    Administration of cadmium (Cd) significantly increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney tissues. Cadmium also caused a significant alteration in hepatic and renal functional markers in serum viz. total protein, albumin, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were severe vascular and sinusoidal congestion with diffuse degenerative changes and mononuclear infiltration into peripheral areas, while the kidney showed vascular and glomerular congestion, cloudy swelling of tubular epithelium. Coadministration of ethonolic extract of T. terrestris or vitamin E along with Cd significantly reversed the Cd induced changes along with significant reduction in Cd load.

  20. The Antidiabetic Activity of Curry Leaves “Murraya Koenigii” on the Glucose Levels, Kidneys, and Islets of Langerhans of Rats with Streptozotocin Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Imad M Al-Ani

    2017-08-01

    Full Text Available Background: The aims of this study were to explore the antihyperglycemic effect of curry leaves, Murraya koenigii "MK" aqueous extract, and to examine its possible protective effects on the islets of Langerhans and kidneys of streptozotocin (STZ diabetic rats. Methods: Thirty healthy adult male Sprague Dawley rats were randomized into five groups (n=6; normal control, normal treated with "MK" control, diabetic control (non-treated with "MK", diabetic treated with 200 mg/kg MK aqueous leaf extract and diabetic treated with 400 mg/kg MK aqueous leaf extract. Blood glucose levels and body weight were monitored gravimetrically. The animals were sacrificed on the 30th day; the kidney and pancreatic tissues were processed for histological studies. Results: The diabetic group showed considerable loss of body weight and increase in blood glucose levels and degeneration of the glomeruli and renal convoluted tubules and atrophied islets with disintegration of β-cells. Treatment of diabetic rats with MK extract showed significant (p < 0.001 improvement in blood glucose levels and body weight gain. The MK extract also caused an improvement in tissue injury induced by STZ injection in the kidney and islets of Langerhans. Conclusions: These findings highlighted the beneficial effects of MK aqueous extract against cellular oxidative damage in STZ-induced diabetic rats.

  1. Dietary Protein Intake in a Multi-ethnic Asian Population of Healthy Participants and Chronic Kidney Disease Patients.

    Science.gov (United States)

    Teo, Boon Wee; Toh, Qi Chun; Xu, Hui; Yang, Adonsia Y T; Lin, Tingxuan; Li, Jialiang; Lee, Evan J C

    2015-04-01

    Clinical practice guidelines recommend different levels of dietary protein intake in predialysis chronic kidney disease (CKD) patients. It is unknown how effectively these recommendations perform in a multi-ethnic Asian population, with varied cultural beliefs and diets. We assess the profi le of protein intake in a multi-ethnic Asian population, comparing healthy participants and CKD patients. We analysed the 24-hour urine collections of the Asian Kidney Disease Study (AKDS) and the Singapore Kidney Function Study (SKFS) to estimate total protein intake (TPI; g/day). We calculated ideal body weight (IDW; kg): 22.99 × height2 (m). Standard statistical tests were applied where appropriate, and linear regression was used to assess associations of continuous variables with protein intake. There were 232 CKD patients and 103 healthy participants with 35.5% diabetics. The mean TPI in healthy participants was 58.89 ± 18.42 and the mean TPI in CKD patients was 53.64 ± 19.39. By US National Kidney Foundation (NKF) guidelines, 29/232 (12.5%) of CKD patients with measured glomerular filtration rate (GFR) patients had TPI-IDW >0.75g/kg/ day. By American Dietetic Association (ADA) guidelines, 34.7% (44/127) of CKD patients with GFR patients with GFR protein intake of between 0.3 to 0.5 g/kg/day. A total of 21.9% (25/114) of diabetic CKD patients had protein intake between 0.8 to 0.9 g/kg/day. On average, the protein intake of most CKD patients exceeds the recommendations of guidelines. Diabetic CKD patients should aim to have higher protein intakes.

  2. Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

    Directory of Open Access Journals (Sweden)

    Noeman Saad A

    2011-08-01

    Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

  3. Effect of embelin on lithium-induced nephrogenic diabetes insipidus in albino rats

    Directory of Open Access Journals (Sweden)

    Ashish K Sahu

    2012-10-01

    Full Text Available Objective: To evaluate the nephroprotective and anti-polyuric role of embelin on lithium induced nephrogenic diabetes insipidus (NDI in albino rats. Methods: NDI induced by lithium chloride (4 meq/kg/day, i.p. for 6 days which leads to huge amount of urine excretion. After induction of NDI, embelin (50 and 100mg/kg was administered orally, once daily for 21 day in rats and N-acetyl cysteine (10mg/kg, twice daily, i.p. was used as a standard drug for treatment of NDI. The body weight, urine protein, urine creatinine, plasma creatinine, blood urea nitrogen were assessed at 0, 7, 14 and 21 day. At the end of the study glutathione (GSH content in kidney was assessed and histopathology of kidney was performed. Results: Embelin 50 and 100 mg/ kg showed increase in the body weight and decrease in plasma and urine creatinine, blood urea nitrogen levels, and urine protein level. Embelin acts as a potent antioxidant; it increases the level of glutathione in kidney. Histopathological examination of the kidney indicated that embelin 50 and 100 mg/kg were reduced the vascular degeneration of tubules as well as slight degeneration and dilatation of renal tubules, however N-actyl cysteine (NAC treated rats showed normal glomeruli and renal tubule with slight degeneration. Conclusions: Embelin seemed to be effective in NDI by its predominant effect on promoting antioxidant status and decrease the urine excretion may be due to the blocking of sodium channels.

  4. A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin.

    Science.gov (United States)

    Schurek, Eva-Maria; Völker, Linus A; Tax, Judit; Lamkemeyer, Tobias; Rinschen, Markus M; Ungrue, Denise; Kratz, John E; Sirianant, Lalida; Kunzelmann, Karl; Chalfie, Martin; Schermer, Bernhard; Benzing, Thomas; Höhne, Martin

    2014-04-18

    Mutations in the NPHS2 gene are a major cause of steroid-resistant nephrotic syndrome, a severe human kidney disorder. The NPHS2 gene product podocin is a key component of the slit diaphragm cell junction at the kidney filtration barrier and part of a multiprotein-lipid supercomplex. A similar complex with the podocin ortholog MEC-2 is required for touch sensation in Caenorhabditis elegans. Although podocin and MEC-2 are membrane-associated proteins with a predicted hairpin-like structure and amino and carboxyl termini facing the cytoplasm, this membrane topology has not been convincingly confirmed. One particular mutation that causes kidney disease in humans (podocin(P118L)) has also been identified in C. elegans in genetic screens for touch insensitivity (MEC-2(P134S)). Here we show that both mutant proteins, in contrast to the wild-type variants, are N-glycosylated because of the fact that the mutant C termini project extracellularly. Podocin(P118L) and MEC-2(P134S) did not fractionate in detergent-resistant membrane domains. Moreover, mutant podocin failed to activate the ion channel TRPC6, which is part of the multiprotein-lipid supercomplex, indicative of the fact that cholesterol recruitment to the ion channels, an intrinsic function of both proteins, requires C termini facing the cytoplasmic leaflet of the plasma membrane. Taken together, this study demonstrates that the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of the plasma membrane to mediate cholesterol binding and contribute to ion channel activity, a prerequisite for mechanosensation and the integrity of the kidney filtration barrier.

  5. Muscle and liver glycogen, protein, and triglyceride in the rat

    DEFF Research Database (Denmark)

    Richter, Erik; Sonne, Bente; Joensen Mikines, Kari

    1984-01-01

    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  6. Prion Protein Promotes Kidney Iron Uptake via Its Ferrireductase Activity*

    Science.gov (United States)

    Haldar, Swati; Tripathi, Ajai; Qian, Juan; Beserra, Amber; Suda, Srinivas; McElwee, Matthew; Turner, Jerrold; Hopfer, Ulrich; Singh, Neena

    2015-01-01

    Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion disorders, a group of neurodegenerative conditions associated with the conversion of prion protein (PrPC) from its normal conformation to an aggregated, PrP-scrapie (PrPSc) isoform. Alteration of iron homeostasis is believed to result from impaired function of PrPC in neuronal iron uptake via its ferrireductase activity. However, unequivocal evidence supporting the ferrireductase activity of PrPC is lacking. Kidney provides a relevant model for this evaluation because PrPC is expressed in the kidney, and ∼370 μg of iron are reabsorbed daily from the glomerular filtrate by kidney proximal tubule cells (PT), requiring ferrireductase activity. Here, we report that PrPC promotes the uptake of transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly NTBI by PT cells in vitro. Thus, uptake of 59Fe administered by gastric gavage, intravenously, or intraperitoneally was significantly lower in PrP-knock-out (PrP−/−) mouse kidney relative to PrP+/+ controls. Selective in vivo radiolabeling of plasma NTBI with 59Fe revealed similar results. Expression of exogenous PrPC in immortalized PT cells showed localization on the plasma membrane and intracellular vesicles and increased transepithelial transport of 59Fe-NTBI and to a smaller extent 59Fe-Tf from the apical to the basolateral domain. Notably, the ferrireductase-deficient mutant of PrP (PrPΔ51–89) lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of PrPC to a detergent-insoluble form, limiting iron uptake. Together, these observations suggest that PrPC promotes retrieval of iron from the glomerular filtrate via its ferrireductase activity and modulates kidney iron metabolism. PMID:25572394

  7. Tumor-associated proteins in rat submandibular gland induced by DMBA and irradiation

    International Nuclear Information System (INIS)

    Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

    1997-01-01

    This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

  8. A Mechanism for the induction of renal tumours in male Fischer 344 rats by short-chain chlorinated paraffins.

    Science.gov (United States)

    Warnasuriya, Gayathri D; Elcombe, Barbara M; Foster, John R; Elcombe, Clifford R

    2010-03-01

    Short-chain chlorinated paraffins (SCCPs) cause kidney tumours in male rats, but not in female rats or mice of either sex. Male rat-specific tumours also occur in rats dosed with a range of compounds including 1,4- dichlorobenzene (DCB) and d-limonene (DL). These compounds bind to a male rat-specific hepatic protein, alpha-2-urinary globulin (α2u), and form degradationresistant complexes in the kidney. The resulting accumulation of α2u causes cell death and sustained regenerative cell proliferation, which in turn leads to the formation of renal tumours. To investigate whether the SCCP, Chlorowax 500C (C500C), causes tumours via the accumulation of α2u male rats were orally dosed with either C500C (625 mg/kg of body weight), DCB (300 mg/kg of body weight), or DL (150 mg/kg of body weight) for 28 consecutive days. An increase in renal α2u and cell proliferation was observed in DCB- and DL-treated rats but not in C500C-treated rats. C500C caused peroxisome proliferation and a down-regulation of α2u synthesis in male rat liver. This down-regulation occurred at the transcriptional level. Since less α2u was produced in C500C-treated rats, there was less available for accumulation in the kidney hence a typical α2u nephropathy did not appear. However, the administration of a radiolabelled SCCP, [14C]polychlorotridecane (PCTD), to male rats demonstrated its binding to renal α2u. Thus, it is possible that SCCPs bind to α2u and cause a slow accumulation of the protein in the kidney followed by delayed onset of α2u nephropathy. As a consequence of these findings in the current experiments, while evidence exists implicating α2u-globulin in the molecular mechanism of action of the C500C, the classic profile of a α2u-globulin nephropathy seen with other chemicals such as DCB and DL was not reproduced during this experimental protocol.

  9. Kinetic parameters of protein metabolism in rats during protein-free feeding

    International Nuclear Information System (INIS)

    Krawielitzki, K.; Schadereit, R.; Wuensche, J.

    1987-01-01

    16 male rats of 100 g live weight were given 50 mg of a mixture containing 15 N-labelled amino acids as a single dose within a protein-free feeding period. Following this the 15 N excretion in feces and urine as well as the development of the 15 N excess in different organs and tissues were estimated over 3 days by slaughtering the animals within given 7 time intervals. Using a 3 pool model and the computer program for the interpretation of 15 N tracer experiments by Toewe et al. (1984), kinetic parameters such as the rate of protein synthesis, protein breakdown and the rate of reutilization were calculated. Despite a negative N balance (- 41.8 mg N/d) under protein-free conditions the protein metabolism of the rat shows high dynamics characterized by a high flux rate (225 mg N/d) and a high rate of body protein synthesis (181 mg/d). The reutilization was 85 %. Depending on time the 15 N excess in the tested organs and tissues showed significant differences and seems to demonstrate that under these conditions protein synthesis mainly takes place in the most important organs (e.g. intestinal tract, liver). Under protein-free feeding conditions protein synthesis and protein breakdown of the whole body seems to be slightly increased in comparison to N balanced feeding conditions. (author)

  10. Cloning and expression of a rat brain α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H.

    1991-01-01

    The authors isolated a cDNA clone (RBα 2B ) and its homologous gene (GRα 2B ) encoding an α 2B -adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor (α 2 -C4) and divergent from the rat kidney nonglycosylated α 2B subtype (RNGα 2 ). Transient expression of RBα 2B in COS-7 cells resulted in high-affinity saturable binding for [ 3 H]rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine > yohimbine > prazosin > oxymetazoline, with a prazosin-to-oxymetazoline K i ratio of 0.34. This profile is characteristic of the α 2B -adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GRα 2B may be transcriptionally active. These findings show that rat brain expresses an α 2B -adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated α 2B subtype. Thus the rat expresses at least two divergent α 2B -adrenergic receptors

  11. Morphological aspects of the rat kidney preserved by cold storage. I. Glomerular morphometric changes.

    Science.gov (United States)

    Neagu, S; Chirculescu, A R; Ranga, V; Popescu, F

    1983-01-01

    The absolute density of glomeruli in the microscopic field was determined in the rat kidney preserved by cold storage for 24, 48, 72 and 96 hrs in two different media: Sacks (hyperosmolar electrolytic solution of intracellular type) and Plasmagel (gelatin solution 4%). Progressive, statistically significant (p less than 0.01) decrease of glomerular density at 24 and 48 hrs was followed by return to initial values at 96 hrs. Decrease of the glomerular density was greater with Plasmagel.

  12. Nanoscale protein architecture of the kidney glomerular basement membrane

    Science.gov (United States)

    Suleiman, Hani; Zhang, Lei; Roth, Robyn; Heuser, John E; Miner, Jeffrey H; Shaw, Andrey S; Dani, Adish

    2013-01-01

    In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. DOI: http://dx.doi.org/10.7554/eLife.01149.001 PMID:24137544

  13. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    OpenAIRE

    Hassina Khaldoun Oularbi

    2014-01-01

    Lambda-cyhalothrin (LCT) is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administ...

  14. Investigation into the combined effects of ethanol and cadmium on rat liver and kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Hopf, G.; Boecker, R.; Bischoff, J.; Werner, M.G.; Estler, C.J. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie)

    1990-08-01

    To examine the combined hepatoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearnace. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa. (orig.).

  15. Receptors for insulin-like growth factor II (IGF-II) in the rat kidney glomerulus

    International Nuclear Information System (INIS)

    Haskell, J.F.; Pillion, D.J.; Meezan, E.

    1986-01-01

    Renal glomeruli were isolated by a technique involving renal perfusion with a solution containing magnetic iron oxide particles, followed by homogenization, sieving and isolation over a strong magnet. Isolated glomeruli were treated with 1% Triton X-100 to solubilize plasma membrane components while insoluble basement membrane components were removed by centrifugation. [ 125 I]Insulin-like growth factor-II (IGF-II) binding to this preparation was competitively inhibited by increasing amounts of unlabelled IGF-II, with 50% inhibition of binding observed at an IGF-II concentration of 1 ng/ml. [ 125 I]IGF-II was covalently cross-linked to its receptor with disuccinimidyl suberate in two tissues known to contain IGF-II receptors, the rat chondrosarcoma chondrocyte and the rat kidney tubule, as well as in rat renal glomeruli. In all three cases, a specific high-molecular weight (Mr = 255,000) band could be identified on autoradiograms of dodecyl sulfate polyacrylamide gels. These results indicate that the rat glomerulus contains a high-affinity receptor for IGF-II. This finding is consistent with the hypothesis that IGF-II plays a role in glomerular growth and differentiation

  16. Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.

    Science.gov (United States)

    Rodríguez-Gómez, Isabel; Manuel Moreno, Juan; Jimenez, Rosario; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Wangensteen, Rosemary; Vargas, Félix

    2015-12-01

    This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney. The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats. Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β-Catenin Signaling Pathway in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Lu Bai

    2017-01-01

    Full Text Available The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH. Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3β (S9, and β-catenin expression were decreased in the signaling pathway, but GSK3β level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-β1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/β-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.

  18. Impact of vitamin D status and obesity on C-reactive protein in kidney-transplant patients

    DEFF Research Database (Denmark)

    Ewers, B.; Gasbjerg, A.; Zerahn, B.

    2008-01-01

    and Patients: Data were collected between December 2005 and April 2006 from 161 adult (aged >18 years) kidney-transplant patients (mean age, 53.1 years; SD, 11.5 years; females/males, 78/83), with a median kidney-graft age of 7.0 years and serum CRP levels :... was found. Fat mass correlated positively with CRP, suggesting that obesity may increase the risk of cardiovascular disease and chronic allograft rejection in kidney-transplant patients. (C) 2008 by the National Kidney Foundation, Inc Udgivelsesdato: 2008/5......Objective: We examined whether vitamin D status and obesity are associated with low-grade systemic inflammation, as assessed by serum concentrations of C-reactive protein (CRP) in an adult population of kidney-transplant patients. Design: This was a single-center, cross-sectional study. Setting...

  19. Effect of altered thyroid states on the distribution of intraperitoneally injected cadmium-109 in rats

    International Nuclear Information System (INIS)

    Mann, S.J.

    1975-01-01

    Metals bind to proteins in the blood and are transported in this bound state. The synthesis of proteins is altered in disease states. There may be an increase, a decrease, or a change in the protein fraction makeup, depending on the type and severity of the disease. Total protein synthesis is increased in hyperthyroidism; decreased in hypothyroidism. These changes alter the uptake and distribution of minerals and metals. This study was designed to determine the effect of altered thyroid states on the distribution of cadmium, a toxic environmental pollutant, in rats. The main experiment consisted of injecting rats with Cd-109 after 15 days of drug pretreatment for induction of hypothyroidism and hyperthyroidism. Cadmium levels in the samples were expressed as percentage of activity per organ (P) and percentage of activity per gram of tissue (A). The results showed that drug treatment affected organ weights. Hypothyroid livers weighed significantly less than hyperthyroid and euthyroid livers. Kidney and spleen weights of all three treatment groups were significantly different from each other. Those of hypothyroid rats weighed the least; those of hyperthyroid rats weighed the most. Expressed as P values, livers of the three treatment groups were not different, but hyperthyroid kidneys and spleens had significantly higher levels of cadmium. The A values of hypothyroid livers, kidneys, and spleens were higher than those of the other two treatment groups. Bone, muscle, testes, and blood samples showed extensive variability, and for this reason statistical analyses were not run. There were trends, but it was evident that the overall treatment effects on cadmium levels in these tissues were negligible

  20. Attenuation of renovascular damage in Zucker diabetic fatty rat by NWT-03, an egg protein hydrolysate with ACE- and DPP4-inhibitory Activity.

    Directory of Open Access Journals (Sweden)

    Yumei Wang

    Full Text Available BACKGROUND: Dipeptidyl peptidase 4 (DPP4 and angiotensin-converting enzyme (ACE are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker diabetic fatty (ZDF rats. Comparisons were made to rats treated with vildagliptin (VIL, included as a positive control for the effect of DPP4 inhibition. METHODS: ZDF rats received NWT-03 (1 g/kg/day or VIL (3 mg/kg/day from 10 to 25 weeks of age. Metabolic and renal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro-inflammatory/fibrotic markers (RT-PCR and Western blotting; and the aorta was removed for studies of endothelium-dependent relaxation (EDR. FINDINGS: Hyperinsulinemic ZDF rats typically developed signs of type-2 diabetes and renovascular damage, as evidenced by albuminuria, glomerulosclerosis, and impaired EDR. Neither NWT-03 nor VIL improved metabolic parameters; for VIL, this was despite a 5-fold increase in glucagon-like peptide (GLP-1 levels. NWT-03 and VIL both reduced renal interleukin (Il-1β/Il-13 mRNA expression and glomerulosclerosis. However, only NWT-03 additionally decreased renal tumor necrosis factor (TNF-α mRNA and P22(phox protein expression, reduced albuminuria, and restored aortic EDR. Indomethacin added to the organ bath instantly improved aortic EDR, indicating a role for cyclooxygenase (COX-derived contractile prostanoids in opposing relaxation in ZDF rats. This indomethacin effect was reduced by NWT-03, but not by VIL, and coincided with decreased renal COX-1/2 protein expression. CONCLUSION AND INTERPRETATION: Long-term supplementation with the egg protein hydrolysate NWT-03 attenuated renovascular damage in this preclinical rat model of type 2 diabetes. A comparison to the DPP4-inhibitor VIL suggests that the effects of NWT-03 were related to both

  1. Characterization of tumour virus proteins, 2

    International Nuclear Information System (INIS)

    Higuchi, T.

    1977-01-01

    The structural protein in murine tumour virus P30 has been measured by radioiummunoassay. The titer of each serum was determined by using as antigen the purified Rauscher viral protein labeled with 125 iodine. Standard competition curve was constructed in order to determine the equivalent of protein to inhibit the precipitation reaction under limited antibody concentration. Competition by purified Kirsten virus suspension normal rat kidney cells, transformed-productive and transformed non-productive cells were measured in homologous and heterologous systems [pt

  2. The Protective Effects of Vitamins C and E on The Oxidative Stress Induced by Sodium Metabisulfite on The Kidney Tissue in Adult Rats

    Directory of Open Access Journals (Sweden)

    Abdolnabi Peyravi

    2016-09-01

    Full Text Available Background & Objective: Sodium metabisulfite which is used as a food preservative in the food industry, has adverse effects on body organs such as kidney and body grouth rate. In this research we have studied the protective effect of Vitamin C and E as antioxidants, on the kidney tissue damage after the consumption of Sodium metabisulfite. Materials & methods: Forty-eight Adult male Wistar rats of 150-200 grams were divided into 6 groups of 8 each. Rats in the experimental groups received Sodium metabisulfite (520 mg / kg body weight by gavage feeding for 30 consecutive days. Also during this period, the experimental groups 2 and 3 received a daily dose of 100 mg / kg vitamins C and E, Respectively. The experimental group 4 received 50 mg / kg vitamin C plus 50 mg / kg of vitamin E by the same root. Control group received only normal diet and water. The placebo received vehicle (drug solvent as well as normal diet and water. At the end of the exprimental period the body growth rate was measured between the groups. The histhopatological examination was performed on the kidney tissue sections. by light microscope Results: The results showed sodium metabisulfite in daily dietary could lead to the kidney tissue damage and reduced body weight in rats (p <0.05. However, vitamins C and E can reduce the kidney tissue damage and allow a normal growth weight (p <0.05. Conclusion: With this study we could conclude that the antioxidant effect of that vitamins C and E have a protective effect on renal damage induced by sodium metabisulfite consumption

  3. Cobalamin and its binding protein in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier

    1989-01-01

    Cobalamin and its binding protein, haptocorrin, are present in rat milk throughout the lactation period. The concentration of cobalamin is approximately 0.3-times the concentration of the unsaturated binding protein. The concentration of the unsaturated cobalamin-binding protein varies between 18...

  4. THE URINE PROTEOME FOR RADIATION BIODOSIMETRY: EFFECT OF TOTAL BODY VERSUS LOCAL KIDNEY IRRADIATION

    Science.gov (United States)

    Sharma, Mukut; Halligan, Brian D.; Wakim, Bassam T.; Savin, Virginia J.; Cohen, Eric P.; Moulder, John E.

    2009-01-01

    Victims of nuclear accidents or radiological terrorism are likely to receive varying doses of ionizing radiation inhomogeneously distributed over the body. Early biomarkers may be useful in determining organ-specific doses due to total body irradiation (TBI) or partial body irradiation. We used liquid chromatography and mass spectrometry to compare the effect of TBI and local kidney irradiation (LKI) on the rat urine proteome using a single 10 Gy dose of X-rays. Both TBI and LKI altered the urinary protein profile within 24 hours with noticeable differences in Gene Ontology categories. Some proteins including fetuin-B, tissue kallikrein, beta-glucuronidase, vitamin D-dependent calcium binding protein and chondroitin sulfate proteoglycan NG2 were detected only in the TBI group. Some other proteins including major urinary protein-1, RNA binding protein 19, neuron navigator, Dapper homolog 3, WD repeat and FYVE domain containing protein 3, sorting nexin-8, ankycorbin and aquaporin were detected only in the LKI group. Protease inhibitors and kidney proteins were more abundant (fraction of total scans) in the LKI group. Up/Uc ratio and urinary albumin abundance decreased in both TBI and LKI groups. Several markers of acute kidney injury were not detectable in either irradiated group. Present data indicate that abundance and number of proteins may follow opposite trends. These novel findings demonstrate intriguing differences between TBI and LKI, and suggest that urine proteome may be useful in determining organ-specific changes caused by partial body irradiation. PMID:20065682

  5. Selenium bioavailability from soy protein isolate and tofu in rats fed a torula yeast-based diet.

    Science.gov (United States)

    Yan, Lin; Graef, George L; Reeves, Philip G; Johnson, LuAnn K

    2009-12-23

    Selenium (Se) is an essential nutrient, and soy is a major plant source of dietary protein to humans. The United States produces one-third of the world's soybeans, and the Se-rich Northern Plains produce a large share of the nation's soybeans. The present study used a rat model to determine the bioavailability of Se from a protein isolate and tofu (bean curd) prepared from a soybean cultivar we recently developed specifically for food grade markets. The soybean seeds contained 2.91 mg Se/kg. Male Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet containing 5 microg Se/kg; after 56 days, they were replenished of Se for an additional 50 days by feeding them the same diet supplemented with 20, 30, or 40 microg Se/kg from soy protein isolate or tofu. l-Selenomethionine (SeMet) was used as a reference. Selenium bioavailability was determined on the basis of the responses of Se-dependent enzyme activities and tissue Se contents, comparing those responses for each soy product to those for SeMet using a slope-ratio method. Dietary supplementation with the protein isolate or tofu resulted in dose-dependent increases in glutathione peroxidase activities in blood and liver and thioredoxin reductase activity in liver, as well as dose-dependent increases in the Se contents of plasma, liver, muscle, and kidneys. These responses indicated an overall bioavailability of approximately 97% for Se from both the protein isolate and tofu, relative to SeMet. These results demonstrate that Se from this soybean cultivar is highly bioavailable in this model and that high-Se soybeans can be good dietary sources of Se.

  6. Plasma Protein Turnover Rates in Rats Using Stable Isotope Labeling, Global Proteomics, and Activity-Based Protein Profiling

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Tyrrell, Kimberly J.; Hansen, Joshua R.; Thomas, Dennis G.; Murphree, Taylor A.; Shukla, Anil K.; Luders, Teresa; Madden, James M.; Li, Yunying; Wright, Aaron T.; Piehowski, Paul D.

    2017-12-06

    Protein turnover is important for general health on cellular and organism scales providing a strategy to replace old, damaged, or dysfunctional proteins. Protein turnover also informs of biomarker kinetics, as a better understanding of synthesis and degradation of proteins increases the clinical utility of biomarkers. Here, turnover rates of plasma proteins in rats were measured in vivo using a pulse-chase stable isotope labeling experiment. During the pulse, rats (n=5) were fed 13C6-labeled lysine (“heavy”) feed for 23 days to label proteins. During the chase, feed was changed to an unlabeled equivalent feed (“light”), and blood was repeatedly sampled from rats over 10 time points for 28 days. Plasma samples were digested with trypsin, and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant was used to identify peptides and proteins, and quantify heavy:light lysine ratios. A system of ordinary differential equations was used to calculate protein turnover rates. Using this approach, 273 proteins were identified, and turnover rates were quantified for 157 plasma proteins with half-lives ranging 0.3-103 days. For the ~70 most abundant proteins, variability in turnover rates among rats was low (median coefficient of variation: 0.09). Activity-based protein profiling was applied to pooled plasma samples to enrich serine hydrolases using a fluorophosphonate (FP2) activity-based probe. This enrichment resulted in turnover rates for an additional 17 proteins. This study is the first to measure global plasma protein turnover rates in rats in vivo, measure variability of protein turnover rates in any animal model, and utilize activity-based protein profiling for enhancing measurements of targeted, low-abundant proteins, such as those commonly used as biomarkers. Measured protein turnover rates will be important for understanding of the role of protein turnover in cellular and organism health as well as increasing the utility of protein

  7. Functional and conformational properties of phaseolin (Phaseolus vulgris L.) and kidney bean protein isolate: a comparative study.

    Science.gov (United States)

    Yin, Shou-Wei; Tang, Chuan-He; Wen, Qi-Biao; Yang, Xiao-Quan

    2010-03-15

    Kidney bean (Phaseolus vulgris L.) seed is an underutilised plant protein source with good potential to be applied in the food industry. Phaseolin (also named G1 globulin) represents about 50 g kg(-1) of total storage protein in the seed. The aim of the present study was to characterise physicochemical, functional and conformational properties of phaseolin, and to compare these properties with those of kidney bean protein isolate (KPI). Compared with kidney bean protein isolate (KPI), the acid-extracted phaseolin-rich protein product (PRP) had much lower protein recovery of 320 g kg(-1) (dry weight basis) but higher phaseolin purity (over 950 g kg(-1)). PRP contained much lower sulfhydryl (SH) and disulfide bond contents than KPI. Differential scanning calorimetry analyses showed that the phaseolin in PRP was less denatured than in KPI. Thermal analyses in the presence or absence of dithiothreitol, in combination with SH and SS content analyses showed the contributions of SS to the thermal stability of KPI. The analyses of near-UV circular dichroism and intrinsic fluorescence spectra indicated more compacted tertiary conformation of the proteins in PRP than in KPI. PRP exhibited much better protein solubility, emulsifying activity index, and gel-forming ability than KPI. The relatively poor functional properties of KPI may be associated with protein denaturation/unfolding, with subsequent protein aggregation. The results presented here suggest the potential for acid-extracted PRP to be applied in food formulations, in view of its functional properties.

  8. NFAT5 is activated by hypoxia: role in ischemia and reperfusion in the rat kidney.

    Directory of Open Access Journals (Sweden)

    Sandra Villanueva

    Full Text Available The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10-18 mmHg; however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO(2 on NFAT5 activity. We found that 1 Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2 Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3 The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O(2. 4 At 2.5% of O(2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5 siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6 siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7 NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla from rats subjected to an experimental model of ischemia and reperfusion (I/R. 7 Experimental I/R increased the NFAT5-target gene aldose reductase (AR. 8 NFAT5 activators (ATM and PI3K were induced in vitro (HEK293 cells and in vivo (I/R kidneys with the same timing of NFAT5. 8 Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage.

  9. High-protein diets and renal status in rats

    OpenAIRE

    Aparicio, V. A.; Nebot, E.; García-del Moral, R.; Machado-Vílchez, M.; Porres, J. M.; Sánchez, C.; Aranda, P.

    2013-01-01

    Introduction: High-protein (HP) diets might affect renal status. We aimed to examine the effects of a HP diet on plasma, urinary and morphological renal parameters in rats. Material and methods: Twenty Wistar rats were randomly distributed in 2 experimental groups with HP or normal-protein (NP) diets over 12 weeks. Results and discussion: Final body weight was a 10% lower in the HP group (p < 0.05) whereas we have not observed differences on food intake, carcass weight and muscle ashes conten...

  10. Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients.

    Science.gov (United States)

    Boxma, Paul Y; van den Berg, Else; Geleijnse, Johanna M; Laverman, Gozewijn D; Schurgers, Leon J; Vermeer, Cees; Kema, Ido P; Muskiet, Frits A; Navis, Gerjan; Bakker, Stephan J L; de Borst, Martin H

    2012-01-01

    Vitamin K is essential for activation of γ-carboxyglutamate (Gla)-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP). Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60) with stable renal function (creatinine clearance 61 [42-77] (median [interquartile range]) ml/min), who were 75 [35-188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP levels (621 vs 852 pmol/L, p500 pmol/L) in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

  11. Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients.

    Directory of Open Access Journals (Sweden)

    Paul Y Boxma

    Full Text Available Vitamin K is essential for activation of γ-carboxyglutamate (Gla-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP. Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60 with stable renal function (creatinine clearance 61 [42-77] (median [interquartile range] ml/min, who were 75 [35-188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP. Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06 and increased dp-ucMGP levels (621 vs 852 pmol/L, p500 pmol/L in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

  12. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Turgut Kara, Neslihan [Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul (Turkey); Sezerman, Osman Ugur [Department of Biostatistics and Medical Informatics, Acibadem University, Istanbul (Turkey); Durasi, İlknur Melis [Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul (Turkey); Chen, Tao [Department of Toxicology, School of Public Health, Soochow University, Suzhou (China); Demirel, Goksun; Alpertunga, Buket [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Chipman, J. Kevin [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); Mally, Angela [Department of Toxicology, University of Würzburg, Würzburg (Germany)

    2015-12-01

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

  13. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

    International Nuclear Information System (INIS)

    Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J. Kevin; Mally, Angela

    2015-01-01

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

  14. Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

    2017-05-01

    Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

  15. Morphological aspects of the rat kidney preserved by cold storage. II. The juxtaglomerular apparatus.

    Science.gov (United States)

    Chirculescu, A R; Neagu, S

    1983-01-01

    The present paper reports on the changes occurring in the juxtaglomerular apparatus during preservation of the rat kidney by cold storage, using two media: Sacks and Plasmagel, to which a membrane stabilizing "cocktail" was added (hydrocortisone, chlorpromazine, epsilonaminocaproic acid - EACA, propranolol). Evident alterations appeared at 48 hours more accentuated at 72 and 96 hours, and more intense when preserved in Plasmagel. The most affected structure in the juxtaglomerular apparatus was the macula densa, the epithelial cells having a more stable structure.

  16. Effects of elevated temperature on protein breakdown in muscles from septic rats

    International Nuclear Information System (INIS)

    Hall-Angeras, M.A.; Angeras, U.H.; Hasselgren, P.O.; Fischer, J.E.

    1990-01-01

    Elevated temperature has been proposed to contribute to accelerated muscle protein degradation during fever and sepsis. The present study examined the effect of increased temperature in vitro on protein turnover in skeletal muscles from septic and control rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham operated. After 16 h, the extensor digitorum longus (EDL) and soleus (SOL) muscles were incubated at 37 or 40 degrees C. Protein synthesis was determined by measuring incorporation of [14C]phenylalanine into protein. Total and myofibrillar protein breakdown was assessed from release of tyrosine and 3-methylhistidine (3-MH), respectively. Total protein breakdown was increased at 40 degrees C by 15% in EDL and by 29% in SOL from control rats, whereas 3-MH release was not affected. In muscles from septic rats, total and myofibrillar protein breakdown was increased by 22 and 30%, respectively, at 40 degrees C in EDL but was not altered in SOL. Protein synthesis was unaffected by high temperature both in septic and nonseptic muscles. The present results suggest that high temperature is not the primary mechanism of increased muscle protein breakdown in sepsis because the typical response to sepsis, i.e., a predominant increase in myofibrillar protein breakdown, was not induced by elevated temperature in normal muscle. It is possible, however, that increased temperature may potentiate protein breakdown that is already stimulated by sepsis because elevated temperature increased both total and myofibrillar protein breakdown in EDL from septic rats

  17. Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats

    International Nuclear Information System (INIS)

    Deaciuc, I.V.; Spitzer, J.A.

    1989-01-01

    The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis

  18. Gene and protein expression of epidermal growth factor measured on the kidney 24 hours after irradiation correlates to late radiation damage

    International Nuclear Information System (INIS)

    Otsuka, Makoto; Hatakenaka, Masamitsu

    2001-01-01

    This study was designed to evaluate the proliferative response of epidermal growth factor (EGF) gene expression as an early indicator of late renal radiation damage. EGF gene expression was measured in the irradiated left kidney of C3H/HeSlc mice using RT-PCR 24 hours after radiation doses of 9, 12, or 15 Gy. In a second experiment, the same radiation doses were administered to the right kidney plus the lower half of the left kidney. The partly irradiated left kidneys were harvested and EGF gene expression was measured. The irradiated whole right kidneys were subjected to immunohistochemical staining for EGF protein. In a third experiment, 12 Gy was administered to the right kidney plus the lower half of the left kidney. The mice underwent left nephrectomy 24 hours after radiation, and the EGF gene expression in the kidney was correlated with the blood urea nitrogen (BUN) level representing late renal functional damage. EGF expression increased in 1 of 10 control mice and in 9 of 10 mice that received 15 Gy. The extent of increase of EGF was dependent on radiation dose. In mice having an increased BUN level after irradiation, 7 of 10 had EGF positive irradiated kidneys. All six mice whose BUN levels were unchanged had EGF-negative irradiated kidneys. EGF protein staining was observed in tubule cells only, not in glomerular cells. The amount of EGF protein staining correlated with radiation dose to some extent. EGF gene expression seems to be a very early indicator of late radiation damage to the kidney. (author)

  19. Absence of functional renal effects of uro-angiographic contrast media on post-ischemic rat kidneys

    International Nuclear Information System (INIS)

    Verbaeys, A.; Maele, G. van; Sy, W. de; Ringoir, S.; Lameire, N.; University Hospital, Ghent; University Hospital, Ghent

    1991-01-01

    Water soluble ionic contrast media (CM) and glucose 5% were administered to Sprague-Dawley rats 36 hours after bilateral warm renal ischemia for 45 min. In all animals (n=28) the renal ischemia caused a decrease of the absolute urinary creatinine output. Intraarterial injection of glucose 5% or CM did not produce different patterns of absolute urinary creatinine output. The serum creatinine increased after 36 hours of reflow. When compared by means of a Mann-Whitney U-test to a normal median serum creatinine obtained in a separate group of 22 normal rats, the increase was statistically significant (p≤0.01). The serum creatinine medians returned to a normal level after 24 hours. It seems therefore that 45 min of warm renal ischemia and 36 hours of reflow is an insufficient challenge to the rat kidney for the detection of the nephrotoxic properties of CM as opposed to when CM are injected during ischemia. (orig.)

  20. Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels

    DEFF Research Database (Denmark)

    Henze, Andrea; Frey, Simone K; Raila, Jens

    2008-01-01

    It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney...... function or type 2 diabetes....

  1. Differential down-regulation of aquaporin-2 in rat kidney zones by peripheral nociceptin/orphanin FQ receptor agonism and vasopressin type-2 receptor antagonism

    DEFF Research Database (Denmark)

    Hadrup, Niels; Petersen, Jørgen S; Windfeld, Søren

    2007-01-01

    ) of the vasopressin type-2 receptor antagonist 5-dimethylamine-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzapine (OPC31260) (32 nmol/kg/min). ZP120 decreased the aquaporin-2 protein level in the rat cortex/outer stripe of outer medulla and decreased apical plasma membrane localization of aquaporin-2......We previously showed that aquaresis induced by the peripherally acting nociceptin/orphanin FQ receptor agonist ZP120 is associated with a decreased protein level of aquaporin-2 (AQP2) in whole-kidney homogenates. We now examined the effects of Ac-RYYRWKKKKKKK-NH(2) (ZP120) (1 nmol/kg/min i.v. for 4...... h) on renal regional expression (cortex/outer stripe of outer medulla, inner stripe of outer medulla, and inner medulla) and subcellular localization of aquaporin-2. Responses to ZP120 were compared to the effects of an equi-aquaretic dose ( approximately 40% inhibition of distal water reabsorption...

  2. Metabolism of serine in growing rats and chicks at various dietary protein levels

    International Nuclear Information System (INIS)

    Tanaka, Hideyuki; Yamaguchi, Michio; Kametaka, Masao

    1976-01-01

    The metabolic fate of the carbon skeleton of L-serine-U- 14 C has been investigated, in vivo and in vitro, in growing rats and chicks fed the diets with various protein calories percents (C %) at 410 kcal of metabolizable energy. The incorporation of 14 C into body protein at 12 hr after the injection of serine- 14 C was about 49% of the injected dose in rats fed the 10 or 15 PC% diet, though the value was reduced in rats fed lower and higher protein diets. The 14 CO 2 production was smaller in rats fed the 10 and 15 PC% diet, and it showed an inverse pattern to that of the 14 C incorporation into body protein. Urinary excretion of 14 C was higher in rats fed 10 and higher PC% diets, whose growth rate and net body protein retention were maximum. In contrast to the case of rats, the incorporation of 14 C into body protein of chicks at 6 hr after the injection was rather reduced in the 15 PC% group. The proportion of 14 C excreted as uric acid was remarkably increased above the 10 PC% group, and about 19% of the injected dose was recovered in the 50 PC% group. The catabolic rate of serine in the liver slices of rats and chicks was increased by high protein diets. These results support the concept that the nutritional significance of metabolism of the carbon skeleton of serine in growing rats and chicks is different from each other, especially at high protein diets. (auth.)

  3. Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection

    NARCIS (Netherlands)

    Rekers, N. V.; Bajema, I. M.; Mallat, M. J. K.; Petersen, B.; Anholts, J. D. H.; Swings, G. M. J. S.; van Miert, P. P. M. C.; Kerkhoff, C.; Roth, J.; Popp, D.; van Groningen, M. C.; Baeten, D.; Goemaere, N.; Kraaij, M. D.; Zandbergen, M.; Heidt, S.; van Kooten, C.; de Fijter, J. W.; Claas, F. H. J.; Eikmans, M.

    2016-01-01

    Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303

  4. Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

    Science.gov (United States)

    Wagoner, M P; Yang, Y; McDuffie, J E; Klapczynski, M; Buck, W; Cheatham, L; Eisinger, D; Sace, F; Lynch, K M; Sonee, M; Ma, J-Y; Chen, Y; Marshall, K; Damour, M; Stephen, L; Dragan, Y P; Fikes, J; Snook, S; Kinter, L B

    2017-01-01

    Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint. These metabolite changes included time and treatment-dependent increases in lactate, taurine, glucose, lactate, alanine, and citrate as well as 9 other known metabolites. As early as 3 days post dose, gentamicin induced increases in urinary albumin, clusterin, neutrophil gelatinase associated protein (NGAL) and total protein concentrations. Urinary albumin, clusterin, and NGAL showed earlier and more robust elevations than traditional kidney safety biomarkers, blood urea nitrogen and serum creatinine. Elevations in urinary kidney injury molecule 1 (KIM-1) were less reliable for detection of gentamicin nephrotoxicity in dogs based on values generated utilizing multiple first-generation, canine-specific KIM-1 immunoassays. The metabolic fingerprint was further evaluated in male and female dogs that received Compound A which induced slightly reversible renal tubular alterations characterized as degeneration/necrosis and concurrent significant increases in urinary taurine amongst other markers. These data support further investigations to demonstrate the value of urinary metabolites, albumin, clusterin, NGAL and taurine as promising markers to enable early detection of DIKI in dogs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney

    Directory of Open Access Journals (Sweden)

    Katakura Masanori

    2012-07-01

    Full Text Available Abstract Background Reactive oxygen species (ROS production induced by α,β-dicarbonyl compounds and advanced glycation end products causes renal dysfunction in patients with type 2 diabetes and metabolic syndrome. Hydrogen-rich water (HRW increases the H2 level in blood and tissues, thus reducing oxidative stress in animals as well as humans. In this study, we investigated the effects of HRW on glucose- and α,β-dicarbonyl compound-induced ROS generation in vitro and in vivo. Methods Kidney homogenates from Wistar rats were incubated in vitro with glucose and α,β-dicarbonyl compounds containing HRW, following which ROS levels were measured. In vivo animal models of metabolic syndrome, SHR.Cg-Leprcp/NDmcr rats, were treated with HRW for 16 weeks, following which renal ROS production and plasma and renal α,β-dicarbonyl compound levels were measured by liquid chromatograph mass spectrometer. Results HRW inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Furthermore, SHR.Cg-Leprcp/NDmcr rats treated with HRW showed a 34% decrease in ROS production. Moreover, their renal glyoxal, methylglyoxal, and 3-deoxyglucosone levels decreased by 81%, 77%, and 60%, respectively. Positive correlations were found between renal ROS levels and renal glyoxal (r = 0.659, p = 0.008 and methylglyoxal (r = 0.782, p = 0.001 levels. Conclusion These results indicate that HRW inhibits the production of α,β-dicarbonyl compounds and ROS in the kidneys of SHR.Cg-Leprcp/NDmcr rats. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.

  6. The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc. against iron-induced functional and histological damages in rat liver and kidney

    Directory of Open Access Journals (Sweden)

    Firouzeh Gholampour

    2017-10-01

    Full Text Available Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7: Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days, FS (ferrous sulfate, 30 mg/kg/day for 14 days, FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection. After 24 hr, blood, urine and tissue samples were collected. Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p

  7. Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

    Science.gov (United States)

    Stenvinkel, Peter; Johnson, Richard J

    2013-11-01

    Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  8. The urine proteome for radiation biodosimetry: effect of total body vs. local kidney irradiation.

    Science.gov (United States)

    Sharma, Mukut; Halligan, Brian D; Wakim, Bassam T; Savin, Virginia J; Cohen, Eric P; Moulder, John E

    2010-02-01

    Victims of nuclear accidents or radiological terrorism are likely to receive varying doses of ionizing radiation inhomogeneously distributed over the body. Early biomarkers may be useful in determining organ-specific doses due to total body irradiation (TBI) or partial body irradiation. The authors used liquid chromatography and mass spectrometry to compare the effect of TBI and local kidney irradiation (LKI) on the rat urine proteome using a single 10-Gy dose of x-rays. Both TBI and LKI altered the urinary protein profile within 24 h with noticeable differences in gene ontology categories. Some proteins, including fetuin-B, tissue kallikrein, beta-glucuronidase, vitamin D-dependent calcium binding protein and chondroitin sulfate proteoglycan NG2, were detected only in the TBI group. Some other proteins, including major urinary protein-1, RNA binding protein 19, neuron navigator, Dapper homolog 3, WD repeat and FYVE domain containing protein 3, sorting nexin-8, ankycorbin and aquaporin were detected only in the LKI group. Protease inhibitors and kidney proteins were more abundant (fraction of total scans) in the LKI group. Urine protein (Up) and creatinine (Uc) (Up/Uc) ratios and urinary albumin abundance decreased in both TBI and LKI groups. Several markers of acute kidney injury were not detectable in either irradiated group. Present data indicate that abundance and number of proteins may follow opposite trends. These novel findings demonstrate intriguing differences between TBI and LKI, and suggest that urine proteome may be useful in determining organ-specific changes caused by partial body irradiation.

  9. Early localization of NPA58, a rat nuclear pore-associated protein

    Indian Academy of Sciences (India)

    We have studied the mitotic reassembly of the nuclear envelope, using antibodies to nuclear marker proteins and NPA58 in F-111 rat fibroblast cells. In earlier studies we have proposed that NPA58, a 58 kDa rat nuclear protein, is involved in nuclear protein import. In this report, NPA58 is shown to be localized on the ...

  10. Rodent malaria in rats exacerbated by milk protein, attenuated by low-protein vegetable diet

    NARCIS (Netherlands)

    Doorne, C.W. van; Eling, W.M.C.; Luyken, R.

    1998-01-01

    Young male Wistar rats were fed a purified, vegetable, low-protein diet containing 6% protein from maize gluten and 2% from soy protein isolate, or comparable diets in which maize gluten was replaced partly or completely by the equivalent amount of a milk protein concentrate. Diets with adequate

  11. Role of Vitamin E and/or High Protein Diet in Modulating Antioxidant Status and Certain Biochemical Changes in Gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Hamza, R.G.; El-Shennawy, H.M.

    2009-01-01

    The main purpose of this study was to examine the modulator effect of vitamin E and/ or high protein diet on the gamma irradiation induced changes in antioxidant Status and certain biochemical parameters. Male albino rats were exposed to 6 Gy (single dose: 0.48 Gy/min) of whole body gamma radiation. Vitamin E (50 mg/kg body weight) was daily administrated to rats via stomach tube for 3 weeks before exposure to gamma radiation continued for 3 weeks post irradiation. Other animals fed daily on high protein diet for 3 weeks before irradiation continued for 3 weeks post irradiation. A combined administration of vitamin E and Feeding on high protein diet was daily applied to another rats group for 3 weeks before irradiation continued for 3 weeks post irradiation. The results obtained revealed that the administration of vitamin E and/or feeding on high protein diet were significantly reduced the changes. induced by gamma irradiation in blood antioxidant enzymes activities (Superoxide dismutase: SOD and Catalase; CAT). concentration of reduced glutathione (GSH). Significant amelioration in the plasma level of total cholesterol (TC), triglycerides (TG), Low density lipoprotein cholesterol (LDL-C) and High density lipoprotein-cholesterol (HDL-C) associated with remarkable decrease in the level of malondialdhyde (MDA) were observed. In addition, significant improvements were observed in liver function parameters (activities of serum aminotransferases (AST, ALT), alkaline phosphatase (ALP) and concentration of total protein and globulin. As well as, the changes in kidney function (serum creatinine and urea levels) were significantly improved. The improvements also extended to include the serum level of uric acid. Accordingly, it could be concluded that. via the adjustment of the antioxidant status, decreasing the releasing of lipid peroxides and the subsequent amending of different biochemical pathways. vitamin E and high protein diet could modulate the radiation injuries in

  12. Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Zhu, Jie; Wang, Hui; Chen, Jingyu; Wei, Wei

    2018-04-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.

  13. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    International Nuclear Information System (INIS)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael

    2015-01-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug

  14. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    Science.gov (United States)

    Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

    2015-04-01

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  15. Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

    Energy Technology Data Exchange (ETDEWEB)

    Roversi, Katiane, E-mail: katianeroversi@gmail.com [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Benvegnú, Dalila M., E-mail: dalilabenvegnu@yahoo.com.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Roversi, Karine, E-mail: karineroversi-@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Trevizol, Fabíola, E-mail: fatrevizol@yahoo.com.br [Universidade Federal de Santa Maria, Programa de Pós-Graduação em Farmacologia (Brazil); Vey, Luciana T., E-mail: luciana.taschetto@hotmail.com [Universidade Federal de Santa Maria (UFSM), Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde (Brazil); Elias, Fabiana, E-mail: fabiana.elias@uffs.edu.br [Universidade Federal da Fronteira Sul (UFFS), Bioquímica e Farmacologia (Brazil); Fracasso, Rafael, E-mail: rafael.fra@hotmail.com [Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas (Brazil); and others

    2015-04-15

    Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

  16. Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

    Science.gov (United States)

    Bouzenna, Hafsia; Samout, Noura; Amani, Etaya; Mbarki, Sakhria; Tlili, Zied; Rjeibi, Ilhem; Elfeki, Abdelfattah; Talarmin, Hélène; Hfaiedh, Najla

    2016-08-01

    Aromatic and medicinal plants are sources of natural antioxidants thanks to their secondary metabolites. Administration of Pinus halepensis L. (Pinaceae family) in previous studies was found to alleviate deleterious effects of aspirin-induced damage on liver and kidney. The present study, carried out on female rats, evaluates the effects of P. halepensis L. essential oil (EOP) on aspirin (A)-induced damage to liver and kidney. The animals used in this study were rats (n=28) divided into 4 groups of 7 each: (1) a control group (C); (2) a group given NaCl for 56 days then treated with (A) (600 mg/kg) for 4 days (A); (3) a group fed with (EOP) for 56 days then (A) for 4 days; and a group fed with only (EOP) for 56 days and given NaCl for 4 days. Estimations of biochemical parameters in blood were determined using kit methods (Spinreact). Lipid peroxidation levels (TBARS), superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) activities were determined. Histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin embeddeding and hematoxylin-eosin staining. Under our experimental conditions, Aspirin at dose 600 mg/kg body weight induced an increase of serum biochemical parameters as well as an oxidative stress in both organs. An increase occurred in TBARS by 108% and 55%, a decrease in SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively, compared to control. Administration of EOP given to rats enabled correction in these parameters. It could be concluded that the treatment with P. halepensis L. essential oil inhibited aspirin-induced liver and kidney damage.

  17. Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs Protected Rats Against Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadzadeh-Vardin

    2015-06-01

    Full Text Available Purpose: Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI. However, the early death of transplanted mesenchymal stem cells (MSCs in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2, in MSCs could protect rats against AKI. Methods: The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI. Results: The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI. Conclusion: These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression.

  18. 54Mn absorption and excretion in rats fed soy protein and casein diets

    International Nuclear Information System (INIS)

    Lee, D.Y.; Johnson, P.E.

    1989-01-01

    Rats were fed diets containing either soy protein or casein and different levels of manganese, methionine, phytic acid, or arginine for 7 days and then fed test meals labeled with 2 microCi of 54Mn after an overnight fast. Retention of 54Mn in each rat was measured every other day for 21 days using a whole-body counter. Liver manganese was higher (P less than 0.0001) in soy protein-fed rats (8.8 micrograms/g) than in casein-fed rats (5.2 micrograms/g); manganese superoxide dismutase activity also was higher in soy protein-fed rats than in casein-fed rats (P less than 0.01). There was a significant interaction between manganese and protein which affected manganese absorption and biologic half-life of 54Mn. In a second experiment, rats fed soy protein-test meals retained more 54Mn (P less than 0.001) than casein-fed rats. Liver manganese (8.3 micrograms/g) in the soy protein group was also higher than that (5.7 micrograms/g) in the casein group (P less than 0.0001), but manganese superoxide dismutase activity was unaffected by protein. Supplementation with methionine increased 54Mn retention from both soy and casein diets (P less than 0.06); activity of manganese superoxide dismutase increased (P less than 0.05) but liver manganese did not change. The addition of arginine to casein diets had little effect on manganese bioavailability. Phytic acid affected neither manganese absorption nor biologic half-life in two experiments, but it depressed liver manganese in one experiment. These results suggest that neither arginine nor phytic acid was the component in soy protein which made manganese more available from soy protein diets than casein diets

  19. [Expression of c-jun protein after experimental rat brain concussion].

    Science.gov (United States)

    Wang, Feng; Li, Yong-hong

    2010-02-01

    To observe e-jun protein expression after rat brain concussion and explore the forensic pathologic markers following brain concussion. Fifty-five rats were randomly divided into brain concussion group and control group. The expression of c-jun protein was observed by immunohistochemistry. There were weak positive expression of c-jun protein in control group. In brain concussion group, however, some neutrons showed positive expression of c-jun protein at 15 min after brain concussion, and reach to the peak at 3 h after brain concussion. The research results suggest that detection of c-jun protein could be a marker to determine brain concussion and estimate injury time after brain concussion.

  20. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)

    2013-09-01

    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  1. The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats.

    Science.gov (United States)

    Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh

    2018-01-01

    Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

  2. Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

    Science.gov (United States)

    Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

    2017-09-01

    Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

    Science.gov (United States)

    Siman, Fabiana D. M.; Silveira, Edna A.; Meira, Eduardo F.; da Costa, Carlos P.; Vassallo, Dalton V.; Padilha, Alessandra S.

    2012-01-01

    Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model. PMID:22529948

  4. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

    Science.gov (United States)

    Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2016-03-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

  5. In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney.

    Science.gov (United States)

    Ncir, Marwa; Saoudi, Mongi; Sellami, Hanen; Rahmouni, Fatma; Lahyani, Amina; Makni Ayadi, Fatma; El Feki, Abdelfattah; Allagui, Mohamed Salah

    2017-09-18

    The present study investigated the in vitro and the in vivo antioxidant capacities of Allium sativum (garlic) extract against deltamethrin-induced oxidative damage in rat's brain and kidney. The in vitro result showed that highest extraction yield was achieved with methanol (20.08%). Among the tested extracts, the methanol extract exhibited the highest total phenolic, flavonoids contents and antioxidant activity. The in vivo results showed that deltamethrin treatment caused an increase of the acetylcholinesterase level (AChE) in brain and plasma, the brain and kidney conjugated dienes and lipid peroxidation (LPO) levels as compared to control group. The antioxidant enzymes results showed that deltamethrin treatment induced a significantly decrease (p < 0.01) in brain and kidney antioxidant enzymes as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) to control group. The co-administration of garlic extract reduced the toxic effects in brain and kidney tissues induced by deltamethrin.

  6. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

    OpenAIRE

    Dunford, L. J.; Sinclair, K. D.; Kwong, W. Y.; Sturrock, C.; Clifford, B. L.; Giles, T. C.; Gardner, D. S.

    2014-01-01

    This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ?145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized ...

  7. Chronic dietary supplementation with soy protein improves muscle function in rats.

    Directory of Open Access Journals (Sweden)

    Ramzi J Khairallah

    Full Text Available Athletes as well as elderly or hospitalized patients use dietary protein supplementation to maintain or grow skeletal muscle. It is recognized that high quality protein is needed for muscle accretion, and can be obtained from both animal and plant-based sources. There is interest to understand whether these sources differ in their ability to maintain or stimulate muscle growth and function. In this study, baseline muscle performance was assessed in 50 adult Sprague-Dawley rats after which they were assigned to one of five semi-purified "Western" diets (n = 10/group differing only in protein source, namely 19 kcal% protein from either milk protein isolate (MPI, whey protein isolate (WPI, soy protein isolate (SPI, soy protein concentrate (SPC or enzyme-treated soy protein (SPE. The diets were fed for 8 weeks at which point muscle performance testing was repeated and tissues were collected for analysis. There was no significant difference in food consumption or body weights over time between the diet groups nor were there differences in terminal organ and muscle weights or in serum lipids, creatinine or myostatin. Compared with MPI-fed rats, rats fed WPI and SPC displayed a greater maximum rate of contraction using the in vivo measure of muscle performance (p<0.05 with increases ranging from 13.3-27.5% and 22.8-29.5%, respectively at 60, 80, 100 and 150 Hz. When the maximum force was normalized to body weight, SPC-fed rats displayed increased force compared to MPI (p<0.05, whereas when normalized to gastrocnemius weight, WPI-fed rats displayed increased force compared to MPI (p<0.05. There was no difference between groups using in situ muscle performance. In conclusion, soy protein consumption, in high-fat diet, resulted in muscle function comparable to whey protein and improved compared to milk protein. The benefits seen with soy or whey protein were independent of changes in muscle mass or fiber cross-sectional area.

  8. Deposition of heavy metals in rat hair and organs using radiotracers. Final report for the period 1983 - 1988

    Energy Technology Data Exchange (ETDEWEB)

    Tykva, R [Czechoslovak Academy of Science, Prague (Czech Republic). Inst. of Organic Chemistry and Biochemistry

    1988-12-31

    The basic scope of the project consisted in the investigation of binding of individual radiometals to soluble proteins isolated from rat hair, epidermis, blood plasma, kidney, and liver and in the study of putative specific transport protein. Using administration of radiometals into rats it was found that lead, mercury, and cadmium are tightly bound to soluble proteins from hair, plasma and tissues. The distribution patterns of Pb-210 in proteins were estimated. the existence of a transport protein has not been unequivocally established. Lead in hair has high affinity towards sulfur-rich proteins, while covalent binding of mercury via sulfhydril groups corresponds to the analysis. 19 refs, 4 figs, 5 tabs.

  9. Deposition of heavy metals in rat hair and organs using radiotracers. Final report for the period 1983 - 1988

    International Nuclear Information System (INIS)

    Tykva, R.

    1988-01-01

    The basic scope of the project consisted in the investigation of binding of individual radiometals to soluble proteins isolated from rat hair, epidermis, blood plasma, kidney, and liver and in the study of putative specific transport protein. Using administration of radiometals into rats it was found that lead, mercury, and cadmium are tightly bound to soluble proteins from hair, plasma and tissues. The distribution patterns of Pb-210 in proteins were estimated. the existence of a transport protein has not been unequivocally established. Lead in hair has high affinity towards sulfur-rich proteins, while covalent binding of mercury via sulfhydril groups corresponds to the analysis. 19 refs, 4 figs, 5 tabs

  10. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Directory of Open Access Journals (Sweden)

    Indu Dhar

    Full Text Available The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs. Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs. HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH, proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  11. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Science.gov (United States)

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  12. Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

    Science.gov (United States)

    Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

    2018-05-30

    Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

    Directory of Open Access Journals (Sweden)

    Victoria L M Herrera

    Full Text Available The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01 and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37 and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28, all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a

  14. Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

    Science.gov (United States)

    Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2013-01-01

    The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of

  15. [Relations between location of elements in periodic table and affinity for the kidneys (author's transl)].

    Science.gov (United States)

    Ando, A; Hisada, K; Ando, I

    1977-10-01

    The distribution of many inorganic compounds in rats was investigated in order to evaluate kidney affinity of inorganic compounds. In these experiments, 30%, 10-20% and 4-10% of administered dose was localized in the kidneys in 203Hg-acetate and 203 Bi-acetate, in H198AuCl4, 103PdCl2, 201TlCl, 210Pd(NO3)2 and H2(127M)TeO3, and in Na2(51)CrO4, 54MnCl2, (114m)InCl3 and 7BeCl2, respectively. Some bipositive ions and anions was hardly taken up into the kidneys. And in many hard acids according to classification of Lewis acids, the uptake rate into the kidneys was usually small. On the other hand, Hg, Au and Bi, which have strong binding power to the protein, showed high uptake rate in the kidneys. As Hg++, Au+ and Bi+++ was soft acids according to classification of Lewis acids, it was thought that these elements would bind strongly to soft base (RSH, RS-) present in the kidney.

  16. Urine liver fatty acid binding protein and chronic kidney disease progression

    DEFF Research Database (Denmark)

    Khatir, Dinah S; Bendtsen, Mette D; Birn, Henrik

    2017-01-01

    , regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L......Excretion of the tubular protein liver fatty acid binding protein (L-FABP) is a potential novel biomarker of renal dysfunction. We examined whether urine L-FABP excretion adds prognostic information to the well-established risk markers, blood pressure (BP), albumin excretion and baseline GFR...

  17. Urea utilization in protein deficient rats

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, N [Hyogo College of Medicine, Nishinomiya, Hyogo (Japan)

    1982-06-01

    Three experiments were performed to investigate the mechanism of urea utilization and the nutritional roles of intestinal flora on the utilization of urea by rats fed with a protein deficient diet. Ammonia content in the small intestine in LPD(low protein diet) group fed with a low protein diet for 2 or 5 weeks was about three of five times higher than that of control group fed with SPD(standard protein diet) after administration of urea (0.2gN/100gB.W.). The /sup 15/N incorporation into plasma protein of LPD group was significantly higher than that of the control group two hours after the administration of /sup 15/N-urea (10 mg/100gB.W.) and higher level of /sup 15/N concentration in plasma protein in LPD group was maintained thereafter. The /sup 15/N incorporation into the amino acids of plasma protein was higher in LPD group than in control group. The /sup 15/N incorporation into the amino acids in portal plasma seemed to be higher in LPD group than in control group one hour after the administration of /sup 15/N-urea (10mg/100gB.W.). However, the /sup 15/N incorporation into each free amino acids was suppressed considerably by the administration of antibiotic mixture. it follows that amino acids may be synthesized from urea in the intestine by intestinal-bacterial action and absorbed from portal vein. From these results, it may be concluded that the ammonia nitrogen converted from urea by the action of intestinal-bacterial urease in the intestine is utilized for the synthesis of essential and nonessential amino acids in protein deficient rats and transfered to the liver through portal vein and utilized for protein synthesis.

  18. Urea utilization in protein deficient rats

    International Nuclear Information System (INIS)

    Tanaka, Noriko

    1982-01-01

    Three experiments were performed to investigate the mechanism of urea utilization and the nutritional roles of intestinal flora on the utilization of urea by rats fed with a protein deficient diet. Ammonia content in the small intestine in LPD(low protein diet) group fed with a low protein diet for 2 or 5 weeks was about three of five times higher than that of control group fed with SPD(standard protein diet) after administration of urea (0.2gN/100gB.W.). The 15 N incorporation into plasma protein of LPD group was significantly higher than that of the control group two hours after the administration of 15 N-urea (10 mg/100gB.W.) and higher level of 15 N concentration in plasma protein in LPD group was maintained thereafter. The 15 N incorporation into the amino acids of plasma protein was higher in LPD group than in control group. The 15 N incorporation into the amino acids in portal plasma seemed to be higher in LPD group than in control group one hour after the administration of 15 N-urea (10mg/100gB.W.). However, the 15 N incorporation into each free amino acids was suppressed considerably by the administration of antibiotic mixture. it follows that amino acids may be synthesized from urea in the intestine by intestinal-bacterial action and absorbed from portal vein. From these results, it may be concluded that the ammonia nitrogen converted from urea by the action of intestinal-bacterial urease in the intestine is utilized for the synthesis of essential and nonessential amino acids in protein deficient rats and transfered to the liver through portal vein and utilized for protein synthesis. (J.P.N.)

  19. Intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep.

    Directory of Open Access Journals (Sweden)

    Ciriaco Ligios

    Full Text Available Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE. The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrP(Sc. We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrP(Sc from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla and occasional interstitial (papilla deposition of PrP(Sc in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrP(Sc. PrP(Sc was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrP(Sc in kidney varied from approximately 27% (subclinical to 73.6% (clinical in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrP(Sc. Here we demonstrate unexpectedly frequent deposition of high levels of PrP(Sc in ovine kidneys of various flocks. Renal deposition of PrP(Sc is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep.

  20. Assessment of protective effects of methylprednisolone and pheniramine maleate on reperfusion injury in kidney after distant organ ischemia: a rat model.

    Science.gov (United States)

    Bayrak, Serdar; Yurekli, Ismail; Gokalp, Orhan; Kiray, Muge; Bademci, Mehmet Senel; Ozcem, Barcin; Besir, Yuksel; Yilik, Levent; Kestelli, Mert; Gurbuz, Ali

    2012-05-01

    Ischemia/reperfusion (I/R) injury of tissues is a common problem that cardiovascular surgeons are faced with. Suppression of inflammation, which plays an important role in the pathogenesis of I/R injury, may reduce this damage. The aim of this study is to investigate the protective effects of methylprednisolone (MP)--a potent anti-inflammatory agent--and pheniramine maleate (FM)--an antihistamine that also has some anti-inflammatory effects--on reperfusion injury of kidneys developing after ischemia of the left lower extremity of rats. Twenty-eight randomly selected male Sprague-Dawley rats weighing 320 to 370 g were divided into four groups, each consisting of seven rats. Group 1 was the control group. Group 2 was the sham group. Rats in group 3 were subjected to I/R and given FM, and rats in group 4 were subjected to I/R and given MP. A tourniquet was applied at the level of the left groin to subjects in group 2 after induction of anesthesia. One hour of ischemia was performed, and no drug was administered. In group 3, half of a total dose of 10 mg/kg FM was administered before ischemia, and the remaining half was given intraperitoneally before reperfusion. In group 4, subjects received a single dose of 50 mg/kg MP intraperitoneally in the 30th minute of ischemia. Kidneys of all subjects were removed after 24 hours. Extracted tissues were investigated regarding histological and biochemical parameters. Malondialdehyde--the end product of lipid peroxidation as an important indicator of I/R injury--levels were significantly lower in group 3 than in group 2 (P 0.05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in group 3 than in group 2 (P < 0.05). However, there was no difference between group 4 and group 2 in terms of these activities. Histological examination demonstrated that both MP and FM had protective effects against I/R injury, but this effect was more potent for FM than for MP. FM has a protective

  1. THE SERUM PROTEIN FRACTIONS IN THYMOQUINONE TREATED RATS.

    Science.gov (United States)

    A, Güllü; S, Dede

    2016-01-01

    TQ has been used as treatment and preventive agent for many diseases over the years. The goal of this study was to investigate the effects of TQ supplement on fractions of serum proteins. Fourteen male Wistar-Albino rats (200-250 g weight) were used as material for two groups; (control (C) and thymoquinone (TQ) respectively. Each group contained seven rats. The control group had only corn oil, while the TQ group was dissolved in corn oil. 30 mg/kg/day were given by oral gavage for four weeks. The serum protein fractions were identified using cellulose acetate technique. The total protein level and albumin, α-1, α-2 fractions and A/G ratio have showed no difference between groups (p>0.05). β-globulin fractions of TQ group were higher than control's (pfractions may have originated from elevation or decline synthesis, or activities of containing proteins.

  2. Renal function in streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Jensen, P K; Christiansen, J S; Steven, K

    1981-01-01

    to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow......Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...

  3. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

    NARCIS (Netherlands)

    Huls, M.; Brown, C.D.; Windass, A.S.; Sayer, R.; Heuvel, J.J.M.W. van den; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R.

    2008-01-01

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney,

  4. Kidney stone formation and antioxidant effects of Cynodon dactylon decoction in male Wistar rats.

    Science.gov (United States)

    Golshan, Alireza; Hayatdavoudi, Parichehr; Hadjzadeh, Mousa Al-Reza; Khajavi Rad, Abolfazl; Mohamadian Roshan, Nema; Abbasnezhad, Abbasali; Mousavi, Seyed Mojtaba; Pakdel, Roghayeh; Zarei, Batool; Aghaee, Azita

    2017-01-01

    The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon ( C. dactylon ) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper. Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining. Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon , lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05). A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.

  5. Effect of dietary protein on the excretion of. cap alpha. /sub 2u/, the sex-dependent protein of the adult male rat

    Energy Technology Data Exchange (ETDEWEB)

    Neuhaus, O W; Flory, W

    1975-01-01

    Adult male rates were maintained on normal (20 percent casein), protein-free (0 percent casein), high protein (50 percent casein), deficient protein (20 percent zein), and a supplemented, deficient protein (20 percent zein plus L-lysine and L-tryptophan) diets. Rats on a protein-free diet excreted approximately 1 mg ..cap alpha../sub 2u//24 h compared with a normal of 10-15 mg/24 h. Depleted rats placed on the normal diet showed a rapid restoration of the normal ..cap alpha../sub 2u/ excretion as well as total urinary proteins. Accumulation of ..cap alpha../sub 2u/ in the blood serum was measured in nephrectomized rats. Rats on the protein free diet accumulated only 30 percent of the ..cap alpha../sub 2u/ compared to normals. On a 50 precent casein diet, rats excreted 30-50 mg ..cap alpha../sub 2u//24 h. However, the accumulation was normal in the serum of nephrectomized rats. A high protein diet did not stimulate ..cap alpha../sub 2u/ synthesis but probably increased the renal loss of all urinary proteins. The excretion of ..cap alpha../sub 2u/ on a zein diet was reduced to the same degree as with the protein-free diet. Supplementation with lysine and tryptophan restored the capacity to eliminate ..cap alpha../sub 2u/ to near normal levels. Accumulation of ..cap alpha../sub 2u/ in the serum of nephrectomized rats kept on the zein diets showed that the effect was to suppress the synthesis of the ..cap alpha../sub 2u/. Supplementation restored the biosynthesis of ..cap alpha../sub 2u/. It is concluded that the effect of dietary protein on the excretion of urinary proteins in the adult male rat is caused in a large part by an influence on the hepatic biosynthesis of ..cap alpha../sub 2u/. The biosynthesis of this protein, which represents approximately 30 percent of the total urinary proteins, is dependent on an adequate supply of dietary protein.

  6. Fructus ligustri lucidi ethanol extract improves bone mineral density and properties through modulating calcium absorption-related gene expression in kidney and duodenum of growing rats.

    Science.gov (United States)

    Feng, Xin; Lyu, Ying; Wu, Zhenghao; Fang, Yuehui; Xu, Hao; Zhao, Pengling; Xu, Yajun; Feng, Haotian

    2014-04-01

    Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague-Dawley rats were randomized into four groups and orally administrated for 4 months an AIN-93G formula-based diet supplementing with different doses of FLL ethanol extract (0.40, 0.65, and 0.90 %) or vehicle control, respectively. Then calcium balance, serum level of Ca, P, 25(OH)2D3, 1,25(OH)2D3, osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX-I), and parathyroid hormone, bone microarchitecture, and calcium absorption-related genes expression in duodenum and kidney were analyzed. The results demonstrated that FLL ethanol extract increased BMD of growing rats and improved their bone microarchitecture and mechanical properties. FLL ethanol extract altered bone turnover, as evidenced by increasing a bone formation maker, OCN, and decreasing a bone resorption maker, CTX-I. Intriguingly, both Ca absorption and Ca retention rate were elevated by FLL ethanol extract treatment, possibly through the mechanisms of up-regulating the transcriptions of calcitropic genes in kidney (1α-hydroxylase) and duodenum (vitamin D receptor, calcium transporter calbindin-D9k, and transient receptor potential vanilloid 6). In conclusion, FLL ethanol extract increased bone mass gain and improved bone properties via modulating bone turnover and up-regulating calcium absorption-related gene expression in kidney and duodenum, which could then activate 1,25(OH)2D3-dependent calcium

  7. Aniline-induced nitrosative stress in rat spleen: Proteomic identification of nitrated proteins

    International Nuclear Information System (INIS)

    Fan Xiuzhen; Wang Jianling; Soman, Kizhake V.; Ansari, G.A.S.; Khan, M. Firoze

    2011-01-01

    Aniline exposure is associated with toxicity to the spleen which is characterized by splenomegaly, hyperplasia, fibrosis, and a variety of sarcomas on chronic exposure in rats. However, mechanisms by which aniline elicits splenotoxic responses are not well understood. Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen. However, nitrated proteins remain to be characterized. Therefore, in the current study using proteomic approaches, we focused on characterizing the nitrated proteins in the spleen of aniline-exposed rats. Aniline exposure led to increased tyrosine nitration of proteins, as determined by 2D Western blotting with anti-3-nitrotyrosine specific antibody, compared to the controls. The analyzed nitrated proteins were found in the molecular weight range of 27.7 to 123.6 kDa. A total of 37 nitrated proteins were identified in aniline-treated and control spleens. Among them, 25 were found only in aniline-treated rats, 11 were present in both aniline-treated and control rats, while one was found in controls only. The nitrated proteins identified mainly represent skeletal proteins, chaperones, ferric iron transporter, enzymes, nucleic acids binding protein, and signaling and protein synthesis pathways. Furthermore, aniline exposure led to significantly increased iNOS mRNA and protein expression in the spleen, suggesting its role in increased reactive nitrogen species formation and contribution to increased nitrated proteins. The identified nitrated proteins provide a global map to further investigate alterations in their structural and functional properties, which will lead to a better understanding of the role of protein nitration in aniline-mediated splenic toxicity. - Highlights: → Proteomic approaches are used to identify nitrated proteins in the spleen. → Twenty five nitrated proteins were found only in the spleen of aniline-treated rats. → Aniline exposure led to increased iNOS mRNA and protein

  8. Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats.

    Science.gov (United States)

    Apaydın, Fatma Gökçe; Baş, Hatice; Kalender, Suna; Kalender, Yusuf

    2016-01-01

    Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Specific, high affinity receptors for insulin-like growth factor II in the rat kidney glomerulus

    International Nuclear Information System (INIS)

    Haskell, J.F.; Pillion, D.J.; Meezan, E.

    1988-01-01

    Rat renal glomeruli were isolated by a technique involving kidney perfusion with a solution containing magnetic iron oxide particles, followed by homogenization, sieving, and concentration over a strong magnet. Isolated glomeruli were treated with 1% Triton X-100 to solubilize plasma membrane components, while insoluble basement membrane components were removed by centrifugation. [ 125 I]Insulin-like growth factor II (IGF-II) binding to this preparation was competitively inhibited by increasing amounts of unlabeled IGF-II, with 50% inhibition at an IGF-II concentration of 1 ng/ml. [ 125 I]IGF-II was covalently cross-linked with disuccinimidyl suberate to its receptor in rat renal glomeruli and a specific high mol wt (255,000) band could be identified on autoradiograms of dodecyl sulfate-polyacrylamide gels. [ 125 I]IGF-II binding and cross-linking to this band was inhibited by a polyclonal antibody against the type II IGF receptor. These results demonstrate for the first time that the isolated rat renal glomerulus contains a high affinity receptor for IGF-II

  10. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

    Science.gov (United States)

    Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

    2017-12-11

    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  11. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

    Directory of Open Access Journals (Sweden)

    A. Caires

    2017-12-01

    Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  12. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...... were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response....... Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti...

  13. Nitrogen excretion in rats on a protein-free diet and during starvation

    DEFF Research Database (Denmark)

    Chwalibog, André; Sawosz, Ewa; Niemiec, Tomasz

    2008-01-01

    Nitrogen balances (six days) were determined in male Wistar rats during feeding a diet with sufficient protein or a nearly protein-free diet (n = 2 x 24), and then during three days of starvation (n = 2 x 12). The objective was to evaluate the effect of protein withdrawal on minimum nitrogen...... excretion in urine (UN), corresponding to endogenous UN, during feeding and subsequent starvation periods. The rats fed the protein free-diet had almost the same excretion of urinary N during feeding and starvation (165 and 157 mg/kg W(0.75)), while it was 444 mg/kg W(0.75) in rats previously fed...... with protein, demonstrating a major influence of protein content in a diet on N excretion during starvation. Consequently, the impact of former protein supply on N losses during starvation ought to be considered when evaluating minimum N requirement necessary to sustain life....

  14. Effect of the aqueous extract of Foeniculum vulgare (fennel on the kidney in experimental PCOS female rats

    Directory of Open Access Journals (Sweden)

    Somayyeh Sadrefozalayi

    2014-02-01

    Full Text Available Objective: Foeniculum vulgare seed (F. vulgare is a herbal plant which is used with phytoestrogene compounds for polycystic ovary syndrome (PCOS treatment. In this research, renoprotective effect of the aqueous extract of Foeniculum vulgare (AEF in experimental PCOS female rats is studied. Materials and Methods: Forty female rats were randomly divided into five groups. The first group served as control,was injected with an equivalent volume (0.2 ml of normal saline, and received normal diet. Animals in the second group were non poly cystic ovary syndrome (PCOS rats which were treated with intragastric administration of aqueous extract of F. vulgare (150 mg/kg b.w.. In the third group, the rats were treated with intraperitoneal injection of estradiolvalerate (EV (4 mg in 0.2 ml of sesame oil. The fourth groups were treated with EV and AEF (150mg/kg bw with the same route.  The fifth groups were treated with EV and AEF (100mg/kg bw. After 4 weeks of study, all of the rats were sacrificed, their kidneys tissues were processed for light microscopy, and some biochemical parameters of serum were measured. Results: The mean values of blood urea nitrogen in PCOS rats treated with low dose of AEF and EV and non-treated, was significantly (p

  15. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

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    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  16. Effect of soy protein on obesity-linked renal and pancreatic disorders in female rats

    International Nuclear Information System (INIS)

    Osman, H.F.; El-Sherbiny, E.M.

    2006-01-01

    The purpose of this study was to identify the effect of soy protein based diet on renal and pancreatic disorders in female obese rats. Animals assigned into group I in which 30 rats fed on a balanced diet. Group II contained 30 rats fed on a diet containing 30% fats for 4 weeks. At the end of the 4 th week, one-half of each group was treated as group III which contain 15 rats (half of group I) fed on diet containing 25% soy protein for 3 weeks and represents soy protein group, and the other half served as control. Group IV contained 15 rats (half of group II) fed on a diet containing 25% soy protein for 3 weeks and served as obese + soy protein group, and the other half fed on a normal balanced diet for 3 weeks and represents the obese group. Body weights of rats were recorded every week during the experimental period. Renal and pancreatic functions were measured as urea, creatinine, glomerular filtration rate (creatinine clearance), ammonia, sodium and potassium ions, total protein, albumin, globulin, glucose, insulin and alpha-amylase activity. Feeding with soy protein led to a very high significant increase in urea while creatinine was significantly decreased and creatinine clearance was significantly increased in the groups fed on soy protein. Ammonia concentration was increased in all groups and there was non-significant alteration in sodium and potassium ion concentrations. In soy protein groups (groups III and IV), total protein, albumin and globulin levels were increased. Glucose level was increased in obese rats and significantly decreased in groups III and IV. In group IV, insulin level was decreased which implicated to insulin excess in obesity. Soy protein decreased alpha-amylase activity in groups III and IV as compared to control rats. From these results, soy protein have a direct and protective effect on glomerular disorders and pancreatic secretions. This may be due to isoflavone contents in soy which can modulate the disturbance in metabolism

  17. Glomerular sieving of high molecular weight proteins in proteinuric rats

    International Nuclear Information System (INIS)

    Bertolatus, J.A.; Abuyousef, M.; Hunsicker, L.G.

    1987-01-01

    To characterize the permeability of the glomerular capillary wall to high molecular weight proteins in normal and proteinuric rats, we determined the glomerular sieving coefficients (GSC) of radioiodinated marker proteins of known size and charge by means of a paired label, tissue accumulation method previously validated in this laboratory. In one group of rats (Series A) the GSCs of 125 I-anionic IgG (aIgG-molecular weight [mol wt] 150,000, pI 4.9) and 131 I-neutral IgG (nIgG-pI 7.4 to 7.6) were measured simultaneously. In Series B, the GSC of a second anionic marker, 131 I-human ceruloplasmin (Crp-mol wt 137,000, pI 4.9) was compared to that of 125 I-nIgG. As in the previous report, the labeled proteins were not degraded or deiodinated during the 20 minute clearance period for GSC determination. Within Series A and B, three subgroups of rats were studied: control saline-infused rats, rats made acutely proteinuric by infusion of the polycation hexadimethrine (HDM), and rats with chronic doxorubicin (Adriamycin-Adria) nephrosis. In the control rats, GSCs for the anionic markers aIgG (Series A) or Crp (Series B) were significantly greater than that of nIgG (both series). These large proteins crossed the filtration barrier by a different pathway from that available to smaller neutral molecules the size of albumin, which in our previous study had a much higher GSC than a native, anionic albumin marker. In a third group of control rats only (Series C), the GSCs of native anionic bovine albumin (BSA) and nIgG were compared directly. The GSC of BSA (0.0029) was only slightly larger than the GSC of nIgG (0.0025), indicating that most of the native albumin crosses the glomerular capillary wall via a nonselective pathway similar to that available to nIgG. The results in the control groups are compatible with recently-described heteroporous models of glomerular size selectivity

  18. Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

    DEFF Research Database (Denmark)

    Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

    2016-01-01

    Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary....... In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria...... for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation...

  19. Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats

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    Mayssaa M. Wahby

    2017-12-01

    Full Text Available Bisphenol A is one of the anthropogenic chemicals produced worldwide, currently released into the environment and causes endocrine-disruption. The largest environmental compartments of BPA are abiotic associated with water and suspended solids that becomes an integrated part of the food chain. The present study aimed to examine the possible protective role of Ginkgo biloba extract (GBE, melatonin and their combination against BPA-induced liver and kidney toxicity of male rats. Fifty rats were divided into five equal groups: control, BPA, BPA plus GBE, BPA plus melatonin and BPA plus GBE plus melatonin. The elevated activities of plasma ALT and AST in addition to increased levels of urea and creatinine concomitant with the decreased total plasma protein could reflect the injurious effect of BPA. Liver and kidney levels of TBARS were significantly increased, while GSH, SOD and GPX were decreased in BPA-treated rats. Also, CAT and GST activities were significantly disrupted in the liver and kidney of rats treated with BPA. Moreover, BPA significantly increased the proinflammatory cytokine TNF-α in the liver and kidney tissues. The histopathological analysis confirmed these results. All the previous alterations in the liver and kidney could be ameliorated when BPA-treated rats were co-administrated either with GBE, melatonin or their combination. These natural substances could exhibit protective effects against BPA-induced hepato- and nephrotoxicity owing to their antioxidative and anti-inflammatory potentials. Keywords: Bisphenol A, Ginkgo biloba extract, Melatonin, Lipid peroxidation, Antioxidant enzymes, Histopathological analysis

  20. The administration of renoprotective agents extends warm ischemia in a rat model.

    Science.gov (United States)

    Cohen, Jacob; Dorai, Thambi; Ding, Cheng; Batinic-Haberle, Ines; Grasso, Michael

    2013-03-01

    Extended warm ischemia time during partial nephrectomy leads to considerable renal injury. Using a rat model of renal ischemia, we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury and extend warm ischemia time. A warm renal ischemia model was developed using Sprague-Dawley rats, clamping the left renal artery for 40, 50, 60, and 70 minutes, followed by 48 hours of reperfusion. An improved renoprotective cocktail referred to as I-GPM (a mixture of specific renoprotective growth factors, porphyrins, and mitochondria-protecting amino acids) was administered -24 hours, 0 hours, and +24 hours after surgery. At 48 hours, both kidneys were harvested and examined with hematoxylin and eosin and periodic acid-Schiff stains for the analysis of renal tubular necrosis. Creatinine, protein, and gene expression levels were also analyzed to evaluate several ischemia-specific and antioxidant response markers. I-GPM treated kidneys showed significant reversal of morphologic changes and a significant reduction in specific ischemic markers lipocalin-2, galectin-3, GRP-78, and HMGB1 compared with ischemic controls. These experiments also showed an upregulation of the stress response protein, heat shock protein (HSP)-70, as well as the phosphorylated active form of the transcription factor, heat shock factor (HSF)-1. In addition, quantitative RT-PCR analyses revealed a robust upregulation of several antioxidant pathway response genes in I-GPM treated animals. By histopathologic and several molecular measures, our unique renoprotective cocktail mitigated ischemia-reperfusion injury. Our cocktail minimized oxidative stress in an ischemic kidney rat model while at the same time protecting the global parenchymal function during extended periods of ischemia.

  1. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

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    Slava Malatiali

    2008-01-01

    Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

  2. The effect of zinc on healing of renal damage in rats.

    Science.gov (United States)

    Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

    2017-07-01

    Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

  3. The Renal Protective Effect of Jiangya Tongluo Formula, through Regulation of Adrenomedullin and Angiotensin II, in Rats with Hypertensive Nephrosclerosis

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    Lin Han

    2015-01-01

    Full Text Available We investigated the effect of Jiangya Tongluo (JYTL formula on renal function in rats with hypertensive nephrosclerosis. A total of 21 spontaneously hypertensive rats (SHRs were randomized into 3 groups: valsartan (10 mg/kg/d valsartan, JYTL (14.2 g/kg/d JYTL, and a model group (5 mL/kg/d distilled water; Wistar Kyoto rats comprised the control group (n = 7, 5 mL/kg/d distilled water. Treatments were administered by gavage every day for 8 weeks. Blood pressure, 24-h urine protein, pathological changes in the kidney, serum creatinine, and blood urea nitrogen (BUN levels were estimated. The contents of adrenomedullin (ADM and angiotensin II (Ang II in both the kidney and plasma were evaluated. JYTL lowered BP, 24-h urine protein, serum creatinine, and BUN. ADM content in kidneys increased and negatively correlated with BP, while Ang II decreased and negatively correlated with ADM, but there was no statistically significant difference of plasma ADM between the model and the treatment groups. Possibly, activated intrarenal renin-angiotensin system (RAS plays an important role in hypertensive nephrosclerosis and the protective function of ADM via local paracrine. JYTL may upregulate endogenous ADM level in the kidneys and antagonize Ang II during vascular injury by dilating renal blood vessels.

  4. The urinary excretion of epidermal growth factor in the rat is reduced by aprotinin, a proteinase inhibitor

    DEFF Research Database (Denmark)

    Jørgensen, P E; Raaberg, Lasse; Poulsen, Steen Seier

    1990-01-01

    in vivo is processed by an aprotinin inhibitable proteinase. EGF is produced in the kidneys as a precursor with a molecular weight of approximately 130 kDa. In rat urine, nanomolar amounts of 6 kDa EGF are excreted per 24 h together with small amounts of high molecular weight forms of EGF. During i...... of immunoreactive EGF in the kidney tissue is increased after aprotinin administration (median amount 0.11 pmol EGF/mg protein versus less than 0.04 pmol EGF/mg protein, P less than 0.001). Neither the creatinine clearance, the total urinary protein output, nor the volume of urine produced was affected by aprotinin....

  5. Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

    International Nuclear Information System (INIS)

    Hau, D.M.

    1984-01-01

    The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats

  6. Effects of electroacupuncture on leukocytes and plasma protein in the X-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Hau, D.M.

    The effects of electroacupuncture on leukocytes and plasma protein on the X ray-irradiated rats were investigated in the present study. The results showed that X-irradiation had an evident inhibitory effect on the counts of total leukocytes, lymphocytes and neutrocytes, and the concentration of the total plasma protein, plasma albumin, globulin and alpha- and beta-globulin in X-irradiated rats. The electroacupuncture was able to help the X-irradiated rats to recover the counts of the total leukocyte, lymphocyte and neutrocyte. The electroacupuncture had a helpful tendency to recover the concentration of the total plasma protein, albumin, globulin, and alpha- and beta-globulin in the irradiated rats.

  7. Methyl isobutyl ketone exposure-related increases in specific measures of α2u-globulin (α2u) nephropathy in male rats along with in vitro evidence of reversible protein binding

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Poet, T.S.; Green, S.; Davis, J.; Hughes, B.; Mensing, T.; Sarang, S.S.; Lynch, A.M.; Hard, G.C.

    2015-01-01

    Chronic exposure to methyl isobutyl ketone (MIBK) resulted in an increase in the incidence of renal tubule adenomas and occurrence of renal tubule carcinomas in male, but not female Fischer 344 rats. Since a number of chemicals have been shown to cause male rat renal tumors through the α2u nephropathy-mediated mode of action, the objective of this study is to evaluate the ability of MIBK to induce measures of α2u nephropathy including renal cell proliferation in male and female F344 rats following exposure to the same inhalation concentrations used in the National Toxicology Program (NTP) cancer bioassay (0, 450, 900, or 1800 ppm). Rats were exposed 6 h/day for 1 or 4 weeks and kidneys excised approximately 18 h post exposure to evaluate hyaline droplet accumulation (HDA), α2u staining of hyaline droplets, renal cell proliferation, and to quantitate renal α2u concentration. There was an exposure-related increase in all measures of α2u nephropathy in male, but not female rat kidneys. The hyaline droplets present in male rat kidney stained positively for α2u. The changes in HDA and α2u concentration were comparable to D-limonene, an acknowledged inducer of α2u nephropathy. In a separate in vitro study using a two-compartment vial equilibration model to assess the interaction between MIBK and α2u, the dissociation constant (K d ) was estimated to be 1.27 × 10 −5 M. This K d is within the range of other chemicals known to bind to α2u and cause nephropathy. Together, the exposure-related increase in measures of α2u nephropathy, sustained increase in renal cell proliferation along with an indication of reversible binding of MIBK to α2u, support the inclusion of MIBK in the category of chemicals exerting renal effects through a protein droplet α2u nephropathy-mediated mode of action (MoA)

  8. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

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    Abdel-Tawab H. Mossa

    2015-01-01

    Full Text Available The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT, alkaline phosphatase (ALP, and gamma-glutamyl transferase (GGT, and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.

  9. Radiation induced changes in plasma total protein nitrogen and urinary total nitrogen in desert rodent and albino rats subjected to dietary protein deficiency

    International Nuclear Information System (INIS)

    Roushdy, H.; El-Husseini, M.; Saleh, F.

    1986-01-01

    The effect of gamma-irradiation on plasma total protein nitrogen and urinary total nitrogen was studied in the desert rodent, psammomy obesus obesus and albino rats subjected to dietary protein deficiency. In albino rats kept on high protein diet, the radiation syndrome resulted in urine retention, while in those kept on non-protein diet, such phenomenon was recorded only with the high radiation level of 1170r. Radiation exposure to 780 and 1170r caused remarkable diuresis in psammomys obesus obesus whereas they induced significant urine retention in albino rats. The levels of plasma total protein nitrogen and urinary total nitrogen were higher in albino rats maintained on high protein diet than in those kept on non-protein diet. Radiation exposure caused an initial drop in plasma total protein nitrogen concentration, concomitant with an initial rise in total urinary nitrogen, radiation exposure of psammomys obesus obesus caused significant increase in the levels of plasma protein nitrogen and urinary total nitrogen. Psammomys obesus obesus seemed to be more affected by radiation exposure than did the albino rats

  10. High resolution helium ion scanning microscopy of the rat kidney.

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    William L Rice

    Full Text Available Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details

  11. Embryonic kidney function in a chronic renal failure model in rodents.

    Science.gov (United States)

    Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

    2017-08-01

    Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

  12. Protective effects of nettle (Urtica dioica extract against acute kidney injury induced by gentamycin in the rat

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    سید پژمان مرتضوی

    2017-11-01

    Full Text Available Aminoglycosides are often used in combination with beta-lactam antibiotics and have a rapid bactericidal effect, are available at an affordable cost and have less incidence of resistance, making them a drug of choice for treatment of several life-threatening infections. However, the nephrotoxic effects of aminoglycosides prevent their long term use. The use of herbal extracts in order to decrease injuries of injurious materials has long been considered. The present study was conducted in order to investigate the protective effects of nettle (Urtica dioica extract against gentamicin induced kidney injuries in the rat. Forty five male Wistar rats were divided into 9 groups consisting of: 1-healthy control group, 2- negative control group that received tween 20 (extract solvent, 3- patient control group which received onlygentamicin at 100 mg/kg, experimental healthy groups 4-6 which received nettle extract at 50, 100 and 200 mg/kg and patient experimental groups 7-9 which received nettle extract along with gentamicin at 100 mg/kg. At the end of the experiment (28 days, blood samples were obtained, and the kidneys were removed for histopathologic investigations. The results showed that gentamicin alone induced renal tissue damage and significantly increased the serum levels of creatinine and urea (p

  13. The Effects of Rumex patientia L. and Urtica dioica L. on Some Blood and Urine Parameters, and Liver and Kidney Histology in Diabetic Rats

    OpenAIRE

    GÜNEŞ, Hasan V.

    2014-01-01

    The effects of Rumex patientia and Urtica dioica on levels of blood glucose, plasma amino acids and other parameters, urine excreta, and liver and kidney histology were examined in diabetic rats induced by streptozotocin. Streptozotocin increased blood glucose and changed the levels of amino acids and other parameters, and caused degenerative changes in the liver and kidney. Rumex patientia had some protective effect on these parameters changed by streptozotocin, while Urtica dioci...

  14. Catabolism of 6-ketoprostaglandin F1alpha by the rat kidney cortex.

    Science.gov (United States)

    Pace-Asciak, C R; Domazet, Z; Carrara, M

    1977-05-25

    Homogenates of the rat kidney cortex converted 5,8,9,11,12,14,15-hepta-tritiated 6-ketoprostaglandin F 1alpha into one major product identified by gas chromatography-mass spectrometry of the methoxime-methyl ester trimethylsilyl ether derivative as 6,15-diketo-9,11-dihydroxyprost-13-enoic acid. The sequence of derivatisation i.e. methoximation prior to methylation, was crucial as methylation of 15-keto catabolites of the E, F and 6-keto-F series affords degradation products. The corresponding 15-keto-13,14-dihydro catabolite was formed in much smaller quantities. Time course studies indicated that 6-keto-prostaglandin F1alpha was catabolised at a slower rate (about 2-5 fold) than prostaglandin F1alpha. The catabolic activity was blocked by NADH.

  15. Antioxidant Evaluation of Methanolic Extract of Black Nightshades Ripe Fruits against Technical and Formulated Parathion-Induced Damage in Albino Rats

    International Nuclear Information System (INIS)

    Abdel-Rahiml, E.A.; Abdel-Rahim, G.A.; Atia, A.I.

    2009-01-01

    Parathion in technical or formulated form at a sub-lethal dose of 1/20 LD 50 was applied orally or dermally at 2-day interval for three months to determine its effect on RNA, DNA and protein content as well as RNA ase and DNA ase activity in different organs liver, brain and kidneys of adult male albino rats. Also, serum GOT, GPT and ALP activity as well as serum total soluble protein, albumin, globulin, bilirubin and uric acid content were determined in adult male albino rats (Rattus norvegicus). In addition, the present studies were undertaken to investigate different biological activities of the above parameters of black nightshades (Solanum nigrum L) methanolic extract. Two kinds of experimental works were taken off (antioxidants and protective). The results showed that technical and formulated parathion increased RNA and protein content but the content of DNA was insignificantly decreased in all rat organs tissue (liver, brain and kidneys) relative to control. The activity of RNA ase was also stimulated. In case of liver and kidney functions the present data observed that serum GOT, GPT and ALP activity was stimulated but total soluble protein, albumin and globulin content was decreased but the urea, uric acid and bilirubin content of serum was increased. Also, liver lipid peroxidation was elevated significantly either by technical or formulated parathion (ingested orally or induced dermally). It should be noted that formulated parathion ingested orally was the most effective, but the technical one had the lowest toxicity. The results of the present studies showed that crude methanolic extract of black nightshades ripe fruits has a strong antioxidant activity as showed by DPPH, nitric oxide scavenging, total reducing power, Fenton's reaction and total antioxidant capacity assay. Finally the the methanolic extract of the present medicinal plant observed a valuable influence as a protective agent in vivo in serum, liver, brain and kidneys damage of parathion

  16. Deposition of heavy metals in rat hair and organs using radiotracers

    International Nuclear Information System (INIS)

    Tykva, R.; Votruba, I.; Vesely, J.; Merta, A.; Hanzlik, J.

    1993-01-01

    The basic scope of this Project consisted in the investigation of binding of individual radiometals to soluble proteins isolated form rat hair, epidermis, blood plasma, kidney and liver and in the study of putative specific transport proteins. Several types of substances, labelled with 210 Pb, 203 Hg or 109 Cd, were administered to adult Wistar A male rats kept in metabolic cages. The protein extract was subject to PAGE in the presence of SDS. It was found that lead, mercury and cadmium is tightly bound to soluble proteins from fair, plasma and tissues. The 210 Pb distribution patterns in proteins were estimated. Lead in hair has high affinity towards sulphur-rich proteins, while covalent binding of mercury via sulphhydryl groups corresponds to our analysis. The established and verified methods including investigation of binding of different elements to proteins without radiotracers represents a reliable basis for further studies. (author). 18 refs, 4 figs, 5 tabs

  17. Influence of thyroid disorders on the kidney expression and plasma activity of aminopeptidase A.

    Science.gov (United States)

    Wangensteen, R; Segarra, A B; Ramirez-Sanchez, M; Gasparo, M De; Dominguez, G; Banegas, I; Vargas, F; Vives, F; Prieto, I

    2015-04-01

    Thyroid disorders may affect blood pressure and renal function modifying factors of the plasmatic and kidney renin-angiotensin system such as aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We investigated the expression of AP A in the kidney, as well as its enzymatic activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male rats. Hyperthyroidism was induced by daily subcutaneous injections of tetraiodothyronine. Hypothyroid rats were obtained by administration of methimazole in drinking water. Expression of AP A was determined by Western blot analysis. Plasma AP A activity was measured fluorometrically using glutamyl-β-naphthylamide as substrate. While hyperthyroid rats exhibited lower levels of plasma AP A activity than controls, the kidney of hyperthyroid animals expressed significantly higher AP A than controls and hypothyroid animals. A discrepancy between the high expression of AP A in kidney of hyperthyroid rats and the low activity of AP A measured in plasma and kidney of hyperthyroid animals was found. The posttranslational influence of environmental biochemical factors may be in part responsible for that divergence.

  18. DIFFERENTIAL RESPONSE OF HEAT SHOCK PROTEINS TO UPHILL AND DOWNHILL EXERCISE IN HEART, SKELETAL MUSCLE, LUNG AND KIDNEY TISSUES

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    Pablo C. B. Lollo

    2013-09-01

    Full Text Available Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP, but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric and downhill (predominantly eccentric muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7% and downhill (-7% of inclination. At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK and lactate dehydrogenase (LDH were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal. When the contraction was concentric (uphill and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL-1 in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively. The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus

  19. Conversion of p-tyrosine to p-tyramine in the isolated perfused rat kidney: Modulation by perfusate concentrations of p-tyrosine

    International Nuclear Information System (INIS)

    Brier, M.E.; Bowsher, R.R.; Henry, D.P.; Mayer, P.R.

    1991-01-01

    The authors used the isolated perfused rat kidney to evaluate the role of renal decarboxylation of p-tyrosine as the source of urinary p-tyramine. Kidneys were perfused with concentrations of p-tyrosine ranging from 0.02 mM to 2.0 mM. p-Tyramine was measured by a sensitive and specific radioenzymatic assay. An increase in the perfusate concentration of p-tyrosine resulted in a significant increase in p-tyramine production that was blocked by the addition of NSD-1015, an inhibitor of aromatic-1-amino decarboxylase (AADC). They conclude p-tyrosine is the precursor for the renal production of p-tyramine, renal AADC catalyzes the formation of urinary p-tyramine, synthesized p-tyramine is predominantly excreted in the urine, and p-tyramine synthesis is modulated by the arterial delivery of p-tyrosine to the kidney

  20. Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats

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    Xiaori He

    2015-07-01

    Full Text Available Background/Aims: The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR rats to dietary folic acid supplementation. Method: Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed or 10% protein diet throughout pregnancy and normal feed during lactation. After weaning, Offspring were then fed onto normal feed and normal feed supplemented with 5 mg folic acid/kg feed for a month, this produced 4 dietary groups (maternal diet/ weanling diet: Con, Folic, IUGR and IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein expression of offspring rats were measured at postnatal 2 months and 3 months. Results: Glomerular volume, blood urea nitrogen, 24 hours urine protein were significantly elevated in IUGR rats compared with Con rats but were decreased by dietary folic acid supplementation. p53 protein expression in IUGR rats were significantly higher than that in Con rats, and p53 promoter methylation status in IUGR rats was reduced significantly compared with Con rats. However, the changes in p53 gene expression and DNA methylation status of IUGR rats were reversed by dietary folic acid supplementation. Conclusions: Our study showed for the first time that folic acid supplementation during early period of life could reverse the abnormality in renal p53 methylation status and protein expression, glomerular volume and renal function of IUGR rats offspring.