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.

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

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

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

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

Energy Technology Data Exchange (ETDEWEB)

Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

2015-08-07

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

International Nuclear Information System (INIS)

Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

2015-01-01

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

Toxicity Induced after Subchronic Administration of the Synthetic Food Dye Tartrazine in Adult Rats, Role of Oxidative Stress

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Narges El Golli

2016-04-01

Full Text Available The present study was conducted to evaluate the toxic potential of tartrazine, a food color, in different tissues in adult rat: blood, liver, kidneys, and spleen. Tartrazine was administered orally at a dose of 300 mg/kg of body weight to adult male Wistar rats during a period of 30 days. Tartrazine treatment led to an increase in platelets count, a reduction in peripheral lymphocytes and in spleen T CD8-lymphocytes. Furthermore, tartrazine increased the activities of hepatocellular enzymes and promoted changes in kidney biomarkers. In order to explore the possible mechanism involved, oxidative-stress assessment was performed. Results identified critical oxidative alterations in all tested organs, as shown by the promotion of lipid peroxidation and the modification of endogenous antioxidant-defense enzymes. Thus, tartrazine is able to induce in adult rats’ hematotoxicity, immunotoxicity, and liver and kidney injuries by changing the whole balance between oxidants and antioxidants.

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.

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.

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...

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

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

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

Science.gov (United States)

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

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.

Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

DEFF Research Database (Denmark)

McCarthy, K J; Couchman, J R

1990-01-01

Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

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

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.

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

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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.

A comparison of pediatric and adult kidney donors for adult recipients.

Science.gov (United States)

Pugliese, M R; Ridolfi, L; Nanni Costa, A; Taddei, S; Venturoli, N; Petrini, F

1999-01-01

The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia-Romagna and Piemonte) over an 11-year period. A group of pediatric donors (Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96% and 96% for pediatric donors versus 98% and 92% for adult donors at 1 and 5 years post-transplantation; graft survival 76% and 68% for pediatric donors versus 88% and 74% for adult donors 1 and 5 y post-transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.

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

Leprecan distribution in the developing and adult kidney.

Science.gov (United States)

Lauer, M; Scruggs, B; Chen, S; Wassenhove-McCarthy, D; McCarthy, K J

2007-07-01

The temporal and spatial deposition of extracellular matrix proteins is critical for nephrogenesis and glomerular maturation. We previously characterized leprecan as a novel chondroitin sulfate proteoglycan which has been recently shown to have prolyl hydroxylase activity. In this study, we examine the distribution of leprecan during nephrogenesis and after a hypertrophic stimulus to the adult kidney. During development, leprecan was localized to mesenchymal aggregates, early comma- and S-phase structures as determined by immunohistochemistry and in situ hybridization. Leprecan mRNA was increased in cells around the vascular cleft of the S- and comma-phase glomeruli. Expression was found in podocytes, mesangial cells, and parietal epithelial cells of loop-phase glomeruli. Leprecan mRNA was substantially decreased in the glomeruli of the adult kidney compared to the developing kidney with a uniform distribution between the glomeruli and the tubules. Within adult glomeruli, leprecan was found in the mesangium mesangial matrix, podocytes, and in Bowman's capsule. In response to glomerular hypertrophy, produced by unilateral nephrectomy, leprecan synthesis was increased in the adult kidney. We suggest that the regulated expression of leprecan during glomerular development or hypertrophy coupled with its reported prolyl hydroxylase activity plays a role during basement membrane assembly.

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 ...

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

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

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

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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.

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

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

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.

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

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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.

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

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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.

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

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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.

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

International Nuclear Information System (INIS)

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

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

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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.

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.

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

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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.

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

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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.

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

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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.

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 ...

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

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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.

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

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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.

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

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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.

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 ...

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 ...

The ageing kidney: biochemical and morphological study after irradiation

International Nuclear Information System (INIS)

Franciolini, F.; Becciolini, A.; Torcini, G.; Lanini, A.

1982-01-01

The behaviour of some activities of the kidney was studied both in young-adult and in adult rats exposed to an 8-Gy dose of γ-rays and killed at various intervals after irradiation (both in the morning and in the evening). Brush border and lysosomal enzymes did not show marked differences among control rats of the same age even if adult animals showed levels of maltase, alkaline phosphatase and LAP activities higher than the young-adult group. Moreover, irradiation did not induce typical modifications of the same enzyme activities in young-adult and adult rats. Adult animals showed a reduction in the brush border enzyme activities at 120 hours after irradiation while, at the same interval, lysosomal activities underwent an increase both in young and in adult animals. (orig.) [de

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)

Comparison of 3 kidney injury multiplex panels in rats.

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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.

Histopathological effects of doxorubicin on kidneys in rats

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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.

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

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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.

Uranium XAFS analysis of kidney from rats exposed to uranium.

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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.

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

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....

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

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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.

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)

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...

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

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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.

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

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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.

The Antidiabetic Activity of Curry Leaves “Murraya Koenigii” on the Glucose Levels, Kidneys, and Islets of Langerhans of Rats with Streptozotocin Induced Diabetes

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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.

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

MR imaging of adult glomerulocystic kidney disease

International Nuclear Information System (INIS)

Egashira, K.; Nakata, H.; Hashimoto, O.; Kaizu, K.; University of Occupational and Environmental Health School of Medicine, Kitakyushu

1991-01-01

A 59-year-old man with hypertension and severe renal dysfunction was diagnosed as having adult glomerulocystic kidney disease. MR imaging of the kidney showed a diffuse reduction of the intensity of the renal cortex with a loss of normal cortico-medullary differentiation of T1-weighted images. Numerous small cortical cysts were also demonstrated. These MR findings complemented the results of the biopsy and were useful for making a definitive diagnosis. (orig.)

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

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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.

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

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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.

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

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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.

Normal kidney size and renal cortical thickness of the Korean adults

International Nuclear Information System (INIS)

Chung, Hee Kyung; Hahm, Chang Kok

1974-01-01

1. The kidney size and cortical thickness were measured from intravenous pyelograms of healthy Korean adults of 250 males and 250 females. 2. The measured size and cortical thickness of kidney were following figure (mm). 3. The size of kidney of male is a little larger than female both in vertical length and horizontal width. 4. The renal cortical thickness were not significant in differences between male and female, right and left, in each poles. 5. In the study of distribution of length differences between pairs of kidneys in our series, the length of right kidney is larger in 18.6%, and width in 27.2%. 6. Comparative study is carried out measuring the length of first lumbar vertebral bodies including 4 intervertebral spaces. 7. The site of kidney is larger in the group of greater length of vertebral height. 8. The renal cortical thickness have no significant differences in according to the differences of length of vertebral height, in each poles. 9. Comparing with the western authors, the kidney size of the Korean adult is not smaller than western

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

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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.

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.

Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats

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A. Elkhateeb

2015-01-01

Full Text Available The present study was carried out to evaluate the role of Nigella sativa Linn (NsL oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT, aspartate transaminase (AST, gamma glutamyltransferase (GGT, bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA and a decrease in glutathione peroxidase (GPx levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.

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.

Benefits of a transfer clinic in adolescent and young adult kidney transplant patients.

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McQuillan, Rory F; Toulany, Alene; Kaufman, Miriam; Schiff, Jeffrey R

2015-01-01

Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer

Benefits of a Transfer Clinic in Adolescent and Young Adult Kidney Transplant Patients

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Rory F. McQuillan

2015-12-01

Full Text Available Background: Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. Objective: The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. Methods: We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. Results: The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03. The median change in estimated glomerular

Ultrastructural changes and nestin expression accompanying compensatory renal growth after unilateral nephrectomy in adult rats

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Eladl MA

2017-02-01

Full Text Available Mohamed Ahmed Eladl,1,2 Wael M Elsaed,2,3 Hoda Atef,4 Mohamed El-Sherbiny2 1Department of Basic Medical Sciences, University of Sharjah, Sharjah, United Arab Emirates; 2Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Anatomy and Embryology Department, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia; 4Department of Histology, University of Mansoura, Mansoura, Egypt Background: Several renal disorders affect the glomerular podocytes. Compensatory structural and functional changes have been observed in animals that have undergone unilateral renal ablation. These changes occur as a pliant response to quench the increased functional demand to maintain homeostasis of fluid and solutes. Nestin is an intermediate filament protein present in the glomerular podocytes of the adult kidney and is linked with the maintenance of its foot process structure. Structural changes in the podocytes ultimately restructure the filtration barrier. Very few studies related to the ultrastructural and histopathologic changes of the podocytes are documented. The present study aimed to assess the histopathologic changes at the ultrastructural level in the adapted kidney at different time intervals following unilateral renal ablation in adult rats and its relation with nestin.Methods: Forty-eight rats were divided into four groups (n=12 in each group. The animals of Group A were control naïve rats, while the group B, group C and group D animals underwent left unilateral nephrectomy and the remaining right kidney was removed on days 10, 20 and 30, respectively. Each group included four sham-operated rats, which were sacrificed at the same time as the naïve rats. Each nephrectomized sample was weighed and its sections were subjected to hematoxylin and eosin examination, transmission electron microscopic study as well as immunostaining using the intermediate filament protein nestin.Results: No difference was found

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

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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

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

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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.

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

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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.

Influence of thyroid disorders on the kidney expression and plasma activity of aminopeptidase A.

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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.

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

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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.

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

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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.

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

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...

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.

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

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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.

[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.

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)

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.

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.

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

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

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.

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

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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.

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

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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.

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

Science.gov (United States)

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.

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.

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.

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.

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

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.

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.

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...

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

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Ragy, Merhan Mamdouh

2015-01-01

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

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.

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

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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

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.

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.

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.

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

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

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Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-01-01

The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l −1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation.

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

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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

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.

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

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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.

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.

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.

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.

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

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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

CT findings in adult Wilms' tumor involving both kidneys

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Feijoo, R.; Lasierra, R.; Pina, J.I.; Benito, J.L.

1998-01-01

Wilms' tumor is the most common renal neoplasm during childhood, but it rarely presents in adults and even less frequently involves both kidneys at onset. The preoperative diagnosis is difficult, although it should be suspected (despite the low incidence) in cases of renal masses that contain necrotic tissue, calcification or fat. We report the case of a 32-year-old woman who presented with bilateral kidney mass and lung metastases. The patient had never complained of urinary symptoms prior to this finding. (Author) 12 refs

Uptake of trace elements in adult and suckling rat lenses

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Nabekura, Tomohiro; Ito, Yoshimasa; Minami, Takeshi; Hirunuma, Rieko; Enomoto, Shuichi

2001-01-01

The uptake of trace elements in the lens was compared in adult and suckling rat lenses. Multitracers, including 15 trace elements, As, Be, Co, Fe, Mn, Rb, Rh, Ru, Sc, Se, Sr, Y, V, Zn, and Zr, were incubated with the lenses for 4 hr and their concentrations in the lens were measured. A high uptake rate of Zn was observed in the lenses of both adult and suckling rats in comparison with those of the other elements, and the Zn concentration in the lens of suckling rats was higher than that of adult rats. The uptake rate of Sr was higher in adult rats than in suckling rats. On the other contrary, Rb and Se concentrations in the lens were higher in suckling rats than in adult rats. The present study suggests that the different mechanisms depending on development serve to transport trace elements into the lens. (author)

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

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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.

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

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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.

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

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

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

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....

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

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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.

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

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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

Antioxidant protection of statins in acute kidney injury induced by sepsis

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Franciele do Nascimento Santos

2014-10-01

Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

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

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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.

Percutaneous absorption of triadimefon in the adult and young male and female rat

International Nuclear Information System (INIS)

Knaak, J.B.; Yee, K.; Ackerman, C.R.; Zweig, G.; Wilson, B.W.

1984-01-01

The percutaneous absorption of 14 C-phenoxy ring labeled triadimefon was studied in adult and young male and female Sprague-Dawley rats. Triadimefon was applied (41.1 to 46.4 micrograms/cm2) in 0.2 ml of acetone to areas comprising 3% of the body surface (7.0 to 14.5 cm2). Thirty-six animals were treated at the initiation of each study. Groups of three animals were subsequently killed at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hr after treatment. Skin from the treated area as well as blood, heart, liver, kidneys, remaining carcass, urine, and feces were analyzed for 14 C by scintillation counting techniques. Based on 14 C counts, triadimefon was lost more rapidly from the skin of young animals (t 1/2, 20 to 25 hr) than from the skin of adult animals (t 1/2, 29 to 53 hr). Recovery studies indicated that adult males, adult females, young males, and young females, respectively, absorbed 53, 82, 57, and 52% of the dose. The rest of the dose based on material balance was presumably lost by evaporation. Approximately 2.5 to 3.9% of the dose penetrated the skin in one hour and was available for absorption. The rate of entry triadimefon into blood was 2 to 2.5 times faster for young than that observed in adult animals. Elimination of it from blood was faster in the case of the young animals. Triadimefon was absorbed through the skins of the adult male, adult female, young male, and young female rats, respectively, at rates of 0.20, 0.50, 0.58, and 0.48 micrograms/hr/cm2 of skin

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

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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.

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)

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

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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.

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

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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.

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...

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

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

DEFF Research Database (Denmark)

Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning

2006-01-01

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adre...

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

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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

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

Fetal kidney programming by severe food restriction: effects on structure, hormonal receptor expression and urinary sodium excretion in rats.

Science.gov (United States)

Vaccari, Barbara; Mesquita, Flavia F; Gontijo, Jose A R; Boer, Patricia A

2015-03-01

The present study investigates, in 23-day-old and adult male rats, the effect of severe food restriction in utero on blood pressure (BP), and its association with nephron structure and function changes, angiotensin II (AT1R/AT2R), glucocorticoid (GR) and mineralocorticoid (MR) receptor expression. The daily food supply to pregnant rats was measured and one group (n=15) received normal quantity of food (NF) while the other received 50% of that (FR50%) (n=15). Kidneys were processed to AT1R, AT2R, MR, and GR immunolocalization and for western blotting analysis. The renal function was estimated by creatinine and lithium clearances in 12-week-old offspring. By stereological analyses, FR50% offspring present a reduction of nephron numbers (35%) with unchanged renal volume. Expression of AT1R and AT2R was significantly decreased in FR50% while the expression of GR and MR increased in FR50%. We also verified a pronounced decrease in urinary sodium excretion accompanied by increased BP in 12-week-old FR50% offspring. The current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption, and this might potentiate the programming of adult hypertension. It is plausible to arise in the current study an association between decreasing natriuresis, reciprocal changes in renal AngII and steroid receptors with the hypertension development found in FR50% compared with age-matched NF offspring. © The Author(s) 2013.

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

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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.

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

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)

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

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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

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

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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

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

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Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

2016-04-01

The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for

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

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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.

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

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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...

The Expression Changes of Inflammasomes in the Aging Rat Kidneys.

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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.

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

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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.

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

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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.

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

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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

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.

Autoradiographic localization of benzodiazepine receptors in the rat kidney

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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.

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

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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.

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

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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...

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

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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.

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

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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.

Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats

International Nuclear Information System (INIS)

Pillet, Stephane; Rooney, Andrew A.; Bouquegneau, Jean-Marie; Cyr, Daniel G.; Fournier, Michel

2005-01-01

Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl 2 ) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects

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.)

Self-management interventions for adults with chronic kidney disease: a scoping review.

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Donald, Maoliosa; Kahlon, Bhavneet Kaur; Beanlands, Heather; Straus, Sharon; Ronksley, Paul; Herrington, Gwen; Tong, Allison; Grill, Allan; Waldvogel, Blair; Large, Chantel A; Large, Claire L; Harwood, Lori; Novak, Marta; James, Matthew T; Elliott, Meghan; Fernandez, Nicolas; Brimble, Scott; Samuel, Susan; Hemmelgarn, Brenda R

2018-03-22

To systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD). Community-based. Adults with CKD stages 1-5 (not requiring kidney replacement therapy). Self-management strategies for adults with CKD. Using a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1-5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare. Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework. There was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence. © Article author(s) (or their employer(s) unless otherwise stated in the

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

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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)

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

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)

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

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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.

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

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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.

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

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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.

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

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

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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.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

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Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

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

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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.

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

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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.

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

[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].

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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.

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

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

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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

Effect of dental materials on gluconeogenesis in rat kidney tubules

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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.)

Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

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Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

2017-03-01

Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

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

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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.

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

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

Ligation of the left renal vein in epm1-wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands

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José Carlos Costa Baptista-Silva

Full Text Available OBJECTIVE: The ligation of the left renal vein (LLVR in man is a contraversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. MATERIAL AND METHODS: 64 male adult EPM1-WISTAR rats were used, divided into 8 groups - 4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. RESULTS: We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice.The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance CONCLUSION: Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.

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

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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.

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

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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

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

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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

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

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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.

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

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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.

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

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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

Awareness level of kidney functions and diseases among adults in a Nigerian population

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Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

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

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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.

Effect of turmeric and its active principle curcumin on t(3)-induced oxidative stress and hyperplasia in rat kidney: a comparison.

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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.

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

Influence of iron on plutonium absorption by the adult and neonatal rat

International Nuclear Information System (INIS)

Sullivan, M.F.; Ruemmler, P.S.; Buschbom, R.L.

1986-01-01

To determine how iron affects plutonium absorption, adult rats were gavaged with 238 Pu nitrate (pH 2) after they had been fed an iron-deficient diet or treated with iron supplements. Neonatal rats born to dams on an iron-deficient diet were also gavaged with 238 Pu. An iron-deficient diet resulted in enhanced 238 Pu absorption both in the adults and in neonates born to iron-deficient dams. Ferric iron increased 238 Pu absorption 12-fold in adult rats; injected iron-dextran reduced that increase; gavaged ferrous iron reduced 238 Pu absorption to one-third of the control value. Rat neonates absorbed 30 to 40 times as much 238 Pu as adults; absorption was lowered in groups that received iron supplements: Iron-dextran caused a 50% reduction; ferric iron, 95%; and ferrous iron, greater than 95%. The results demonstrate an effect of the oxidation state of iron on plutonium absorption in adult rats different from that observed in suckling rats. The results suggest that the high rate of 238 Pu absorption by neonatal animals is due not only to the permeability of their intestines but also to their high demand for iron

Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.

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Olowu, Wasiu A; Niang, Abdou; Osafo, Charlotte; Ashuntantang, Gloria; Arogundade, Fatiu A; Porter, John; Naicker, Saraladevi; Luyckx, Valerie A

2016-04-01

Access to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care. We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best reflect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690. We identified 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex. Patients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa. None. Copyright © 2016 Olowu et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

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

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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.

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

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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.

Radiation dose estimates for adults and newborns from tungsten-178: based on distribution data in adult and infant animals

International Nuclear Information System (INIS)

Wiles, H.; Lacy, J.; LeBlanc, A.; Bricker, J.; Watson, E.; Stabin, M.

1987-01-01

Biodistribution and retention of tungsten-178 ( 178 W) were studied in adult and infant animals in order to extrapolate radiation dose estimates to human newborns and adults. Whole body retention and organ distribution of 178 W were determined at 0.5, 2, 8, 24 and 48 hours after blood-pool injection in infant and adult rats. Percent whole body retention and percent organ uptake per gram of tissue were higher in infant than adult rats at each time interval. When extrapolated to humans on the basis of percent injected activity kilogram per gram, most organs, except bone and kidney, showed higher uptake in newborns than adults. Total body radiation dose estimates for humans from 178 w based on these data were: 0.93 mGy/MBq (3.4 rad/mCi) for newborns and 0.024 mGy/MBq (0.089 rad/mCi) for adults. 13 refs.; 5 tabs

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

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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.

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

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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.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

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Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

2017-05-01

Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

Outcomes of adult dual kidney transplants by KDRI in the United States.

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Klair, T; Gregg, A; Phair, J; Kayler, L K

2013-09-01

UNOS guidelines provide inadequate discriminatory criteria for kidneys that should be transplanted as single (SKT) versus dual (DKT). We evaluated the utility of the kidney donor risk index (KDRI) to define kidneys with better outcomes when transplanted as dual. Using SRTR data from 1995 to 2010 of de novo KTX recipients of adult deceased-donor kidneys, we examined outcomes of SKT and DKT stratified by KDRI group ≤1.4 (n = 49 294), 1.41-1.8 (n = 15 674), 1.81-2.2 (n = 6523) and >2.2 (n = 2791). DKT of kidneys with KDRI >2.2 was associated with significantly better overall graft survival [adjusted hazard ratio (aHR) 0.83, 95% confidence interval (CI) 0.72-0.96] compared to single kidneys with KDRI >2.2. DKT was associated with significantly decreased odds of delayed graft function (top 2 KDRI categories) and significantly decreased odds of 1-year serum creatinine level >2 mg/dL (top 3 KDRI categories). Among SKT and DKT from KDRI >2.2 there were 16.1 and 13.9 graft losses per 100 patient follow-up years, respectively. KDRI >2.2 is a useful discriminatory cut-off for the determination of graft survival benefit with the use of DKT; however, the benefit of increased graft years was less than half of single kidneys from donors in the same KDRI range. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

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.

[Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

Science.gov (United States)

Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

2017-12-01

Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

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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.

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.

Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease

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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...

Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats.

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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.

Effects of combined treatment of rats with cadmium and ionizing radiation on nucleic acids in the kidneys, liver and haemopoietic organs

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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)

Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

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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,

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

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Williams, Robert C.; Opelz, Gerhard; Weil, E. Jennifer; McGarvey, Chelsea J.; Chakkera, Harini A.

2017-01-01

Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. ...

In vitro uptake of 75Se-selenite by lens of young and adult rats

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Sladkova, J.; Ostadalova, I.; Babicky, A.; Obenberger, J.

1988-01-01

The uptake was observed of 75 Se-selenite by the lens in Wistar strain rats in adult animals, in 17-day old rats kept with their mothers and in prematurely weaned rats. Also measured was the excretion of 75 Se by the lens of young and adult rats following incubation in the medium with radioselenium. The metabolites were analysed which were discharged by the lens containing 75 Se. In Brattleboro rats the uptake of 75 Se-selenite was also measured by the lens in young and adult rats. The uptake of 75 Se-selenite by the lens in young Wistar rats was found to be 1.6 times higher than by the lens of adult rats and the time course of the radioselenium uptake was slightly different. In the lens of prematurely weaned rats no significant difference was found in the uptake of radioselenium after 4 hours as compared with rats of the same age kept with their mothers. In homozygous Brattleboro rats, a higher uptake of 75 Se-selenite was found as compared with both young and adult heterozygous rats. The time course and the quantity of 75 Se efflux from the lens of young and adult Wistar rats differed significantly after 0.5 hour of pre-incubation. From metabolites containing 75 Se excreted by the lens following preincubation, glutathione selenotrisulfide and a not yet accurately determined fraction with a large share of radioactivity were isolated. The stated results provide yet more proof that selenium cataract is a manifestation of the ontogenic dependence of selenium metabolism in the lens and in the entire organism. (author). 4 tabs., 30 refs

In vivo tracking of magnetically labeled mesenchmal stem cells injected via renal arteries in kidney failure rat

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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)

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

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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.

Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

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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.

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

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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.

Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

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Li, Y Q; Wong, C S

2000-09-01

This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

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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.

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.

Effect of Fenugreek (Trigonella Foenum-Graecum) Supplementation on Radiation-Induced Oxidative Stress in Liver and Kidney of Rats

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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.

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

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

Science.gov (United States)

Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

2016-05-01

Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

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

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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

Ultrasonography of polycystic kidney

International Nuclear Information System (INIS)

Oh, Seung Chul; Cho, Seung Gi; Lee, Kwan Seh; Kim, Kun Sang

1980-01-01

Polycystic disease is defined as a heritable disorder with diffuse involvement of both kidneys. The term 'Polycystic disease' comprises at least two separate, genetically different disease-one with an onset typically in childhood (infantile polycystic disease) and the other with an onset typically in adulthood (adult polycystic disease). Adult polycystic kidney disease is the most common form of cystic kidney disease in humans. Ultrasonography is a very useful noninvasive diagnostic modality in the patient with clinically suspected renal diseases as well as screening test. 14 cases of ultrasonography in patient with polycystic kidney were reviewed. All cases show unilateral or bilateral enlarged kidneys. 7 cases reveal kidneys and liver replaced by multiple cysts of varing size. Screening ultrasonography for a familial tree is reported

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

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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.

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.

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

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

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

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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.

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

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Clint Gray

Full Text Available Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L. Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L, with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]. Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger, member 3 (SLC9A3 together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young.

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

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:

Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

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Shasanka S Panda

2013-01-01

Full Text Available Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.

Science.gov (United States)

Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2016-10-01

The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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.

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

Science.gov (United States)

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.

Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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Jie Wu

Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

International Nuclear Information System (INIS)

Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

2010-01-01

Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 μg/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 μg/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

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

Hand-assisted bilateral nephrectomy in a patient with adult polycystic kidney disease

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Marcello Alves Pinto

Full Text Available CONTEXT: Dominantly autosomal polycystic disease is characterized by multiple bilateral and non-functional cysts, which lead to progressive kidney failure. OBJECTIVE: Our objective was to report on a case of hand-assisted bilateral nephrectomy in a 28-year-old female patient with adult polycystic disease and recurring pyelonephritis in a kidney transplant program. CASE REPORT: A hand-assisted bilateral nephrectomy was performed through a supra-umbilical median incision of approximately 6 cm, and with 3 ports of 10 mm. The length of the surgery was 3 hours and 15 minutes. The kidneys were removed after the aspiration of some cysts through the supra-umbilical incision. Pain control was achieved via the use of analgesics. The blood loss during surgery was 160 ml. During the postoperative period, the patient developed right-side pneumothorax, which was drained with no further occurrence. This drain was kept in place for 48 hours. The length of hospitalization was 4 days.

Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults.

Science.gov (United States)

Lee, Sungchul; Lee, Sangyoon; Harada, Kazuhiro; Bae, Seongryu; Makizako, Hyuma; Doi, Takehiko; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao; Shimada, Hiroyuki

2017-10-01

The aim of the present study was to evaluate the relationship between kidney function with concomitant diabetes or hypertension and frailty in community-dwelling Japanese older adults. The participants were 9606 residents (community-dwelling Japanese older adults) who completed baseline assessments. The estimated glomerular filtration rate (mL/min/1.73 m 2 ) was determined according to the serum creatinine level, and participants were classified into four mutually exclusive categories: ≥60.0 (normal range), 45.0-59.9, 30.0-44.9 and who met three, four or five criteria satisfied the definition of having frailty. Multivariate logistic regression was used to examine the relationships between estimated glomerular filtration rate and frailty. After multivariate adjustment, participants with lower kidney function (estimated glomerular filtration rate hypertension (OR 2.53, 95% CI 1.45-5.12) showed a significantly increased risk of frailty in the lower kidney function group, regardless of multivariate controls. Furthermore, the analyses showed an even greater increase in the risk of frailty in patients with a history of both diabetes and hypertension (OR 3.67, 95% CI 1.13-14.1) CONCLUSIONS: A lower level of kidney function was associated with a higher risk of frailty in community-dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 1527-1533. © 2016 Japan Geriatrics Society.

Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats.

Science.gov (United States)

Al-Numair, Khalid S; Chandramohan, Govindasamy; Veeramani, Chinnadurai; Alsaif, Mohammed A

2015-09-01

The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats. The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal. The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.

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.

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...

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

Science.gov (United States)

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.

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.

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

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

Energy Technology Data Exchange (ETDEWEB)

Worley, Rachel Rogers, E-mail: idz7@cdc.gov [Agency for Toxic Substances and Disease Registry, Division of Community Health Investigations, 4770 Buford Highway, Atlanta, GA 30341 (United States); Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Fisher, Jeffrey [Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Food and Drug Administration, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079 (United States)

2015-12-15

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

International Nuclear Information System (INIS)

Worley, Rachel Rogers; Fisher, Jeffrey

2015-01-01

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

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.

Diabetes and Kidney Disease

Science.gov (United States)

... et.al. Clinical manifestations of kidney disease among US adults with diabetes. Journal of the American Medical Association. 2016;316( ... of Washington, Associate Director, Kidney Research Institute ... The National Institute of Diabetes and Digestive and Kidney Diseases Health Information Center ...

[Effect of tail-suspension on the reproduction of adult male rats].

Science.gov (United States)

Zhou, Dang-xia; Qiu, Shu-dong; Wang, Zhi-yong; Zhang, Jie

2006-04-01

To study the effects on the male reproduction in adult male rats and its mechanisms through simulated weightlessness using tail-suspension, in order to do a basic works of exploring the effects on human being's reproduction in outer space. Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then we examined the weight and morphology of testis, the quality and amount of sperm, also tested the serum hormone by radioimmunoassay and analyzed apoptosis rate of testicular cells by TUNEL in the experimental rats and control rats. After tail-suspension, the weight of testis, the sperm count and sperm motility significantly decreased (P 0.05). These changes were not significant between two experimental groups (P > 0.05). In addition, the seminiferous tubules became atrophy with the reduction of the layers of seminiferous epithelium, and sperm amount in lumens of seminiferous tubules decreased in experimental groups. The above were more remarkable in the 28 d experimental group. Simulating weightlessness has a harmful effect on reproduction of adult male rats. These may be caused by inducing apoptosis. The blocking apoptosis of testicular cells may be useful in improving the harmful effect.

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

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

International Nuclear Information System (INIS)

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

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.

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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

Aging and the Disposition and Toxicity of Mercury in Rats

Science.gov (United States)

Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

2014-01-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg2+), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg2+ in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5 μmol • kg−1 non-nephrotoxic or a 2.5 μmol • kg−1 nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. PMID:24548775

Aging and the disposition and toxicity of mercury in rats.

Science.gov (United States)

Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K

2014-05-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg(2+)), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg(2+) in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5μmol·kg(-1) non-nephrotoxic or a 2.5μmol·kg(-1) nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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...

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.).

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

Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

African Journals Online (AJOL)

Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

Comparison and modification of Pu-239 kinetics in young and adult rats

International Nuclear Information System (INIS)

Volf, V.; Gamer, A.; Laengle, U.

1987-01-01

It is obvious that the biokinetics of bone-seeking radionuclides are influenced by skeletal growth and remodelling, the rate of which in general decreases with increasing age. For plutonium, Mahlum and Sikov (1974) observed that rats injected with Pu-239 as weanlings retained a lower percentage in the liver and more in the bones than the animals injected as adults. However, skeletal Pu-239 was diluted more rapidly in the young rats because of intensive new bone formation and this led to a more pronounced reduction in the accumulation of radiation dose than was the case in adult animals. The aim of the present experiments was to study: a) The age effect on Pu-239 biokinetics in adult rates as influenced by the sex of the animals. b) Early retention and distribution of Pu-239 in the bones of young and adult rats injected with an optimal osteosarcomogenic dose. c) The effectiveness of a delayed prolonged administration of Zn-DTPA in drinking water for the mobilization of injected Pu-239 in rats of various age. 3 refs.; 5 figs.; 1 table

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Science.gov (United States)

Lata, Sneh; Marasa, Maddalena; Li, Yifu; Fasel, David A; Groopman, Emily; Jobanputra, Vaidehi; Rasouly, Hila; Mitrotti, Adele; Westland, Rik; Verbitsky, Miguel; Nestor, Jordan; Slater, Lindsey M; D'Agati, Vivette; Zaniew, Marcin; Materna-Kiryluk, Anna; Lugani, Francesca; Caridi, Gianluca; Rampoldi, Luca; Mattoo, Aditya; Newton, Chad A; Rao, Maya K; Radhakrishnan, Jai; Ahn, Wooin; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Antignac, Corinne; Markowitz, Glen S; Garcia, Christine K; Kiryluk, Krzysztof; Sanna-Cherchi, Simone; Gharavi, Ali G

2018-01-16

The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of

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

Science.gov (United States)

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.

NFAT5 is activated by hypoxia: role in ischemia and reperfusion in the rat kidney.

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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.

The role of long-term label-retaining cells in the regeneration of adult mouse kidney after ischemia/reperfusion injury.

Science.gov (United States)

Liu, Xiangchun; Liu, Haiying; Sun, Lina; Chen, Zhixin; Nie, Huibin; Sun, Aili; Liu, Gang; Guan, Guangju

2016-04-30

Label-retaining cells (LRCs) have been recognized as rare stem and progenitor-like cells, but their complex biological features in renal repair at the cellular level have never been reported. This study was conducted to evaluate whether LRCs in kidney are indeed renal stem/progenitor cells and to delineate their potential role in kidney regeneration. We utilized a long-term pulse chase of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in C57BL/6J mice to identify renal LRCs. We tracked the precise morphological characteristics and locations of BrdU(+)LRCs by both immunohistochemistry and immunofluorescence. To examine whether these BrdU(+)LRCs contribute to the repair of acute kidney injury, we analyzed biological characteristics of BrdU(+)LRCs in mice after ischemia/reperfusion (I/R) injury. The findings revealed that the nuclei of BrdU(+) LRCs exhibited different morphological characteristics in normal adult kidneys, including nuclei in pairs or scattered, fragmented or intact, strongly or weakly positive. Only 24.3 ± 1.5 % of BrdU(+) LRCs co-expressed with Ki67 and 9.1 ± 1.4 % of BrdU(+) LRCs were positive for TUNEL following renal I/R injury. Interestingly, we found that newly regenerated cells formed a niche-like structure and LRCs in pairs tended to locate in this structure, but the number of those LRCs was very low. We found a few scattered LRCs co-expressed Lotus tetragonolobus agglutinin (LTA) in the early phase of injury, suggesting differentiation of those LRCs in mouse kidney. Our findings suggest that LRCs are not a simple type of slow-cycling cells in adult kidneys, indicating a limited role of these cells in the regeneration of I/R injured kidney. Thus, LRCs cannot reliably be considered stem/progenitor cells in the regeneration of adult mouse kidney. When researchers use this technique to study the cellular basis of renal repair, these complex features of renal LRCs and the purity of real stem cells among renal LRCs should be considered.

Role of garlic extract and silymarin compared to dimercaptosuccinic acid (DMSA in treatment of lead induced nephropathy in adult male albino rats

Directory of Open Access Journals (Sweden)

Iman A. El-Khishin

2015-01-01

Full Text Available Lead poisoning has been known as an important disorder that affects individuals through acute, sub-acute and chronic exposure in environmental and occupational settings. This study was conducted to compare the curative role of garlic combined with silymarin versus dimercaptosuccinic acid (DMSA in decreasing lead induced nephrotoxicity in adult male albino rats. The period of lead intoxication extended for 3 months followed by either 1 month treatment with garlic and silymarin or 5 days treatment with DMSA. Lead poisoning caused non-significant difference in kidney function tests (BUN and serum creatinine while, it caused significant elevation in kidney lead level, significant decrease in renal antioxidant enzyme glutathione peroxidase and significant elevation in kidney malondialdehyde. Histologically, lead induced disorganization and shrinkage of glomeruli with sloughing and vaculation of epithelium, widening of Bowman's space and inflammatory infiltration in renal medulla. Treatment by garlic extract combined with silymarin as well as treatment with DMSA resulted in significant improvement in the affected parameters. Also, both methods of treatment resulted in improvement of the histopathological changes. It can be concluded that garlic extract combined to silymarin is comparable to DMSA in amelioration of lead induced nephrotoxicity.

Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

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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.

Morphological aspects of the rat kidney preserved by cold storage. II. The juxtaglomerular apparatus.

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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.

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

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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.

Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults.

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Canney, Mark; O'Connell, Matthew D L; Sexton, Donal J; O'Leary, Neil; Kenny, Rose Anne; Little, Mark A; O'Seaghdha, Conall M

2017-05-04

Impaired orthostatic blood pressure (BP) stabilization is highly prevalent in older adults and is a predictor of end-organ injury, falls, and mortality. We sought to characterize the relationship between postural BP responses and the kidney. We performed a cross-sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years. Beat-to-beat systolic and diastolic BP were measured during a 2-minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (eGFR) categorized as follows (mL/min per 1.73 m 2 ): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); postural BP response merits further study in kidney disease as a potential means of identifying those at risk of hypotension-related events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Fetal development and renal function in adult rats prenatally subjected to sodium overload.

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Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

2009-10-01

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P sodium-overloaded pups showed increased U(Prot24 h) (45%, P sodium-overloaded rats showed increased U(Prot24 h) (27%, P sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Absence of functional renal effects of uro-angiographic contrast media on post-ischemic rat kidneys

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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.)

Kidney transplant survival in pediatric and young adults

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Acott Phil

2011-10-01

Full Text Available Abstract Background There is a perception that kidney transplant recipients transferred from pediatric centers to adult care have an increased risk of graft loss. It is not clear whether young adults transplanted in adult centers also suffer from high graft loss rates. Methods We examined death censored graft survival in 3 cohorts of young patients transplanted at a single center. Pediatric (PED patients transplanted at the pediatric center were compared to a cohort of young adults (YAD; age 18- Results In a multivariate Cox model for death-censored graft survival, PED survival was statistically similar to the YAD (HR 0.86, 95% CI 0.44, 1.7, p = 0.66, however the ADL cohort (HR 0.45, 95% CI 0.25, 0.82, p = 0.009 demonstrated better survival. Admitted non-adherence rates were not different among cohorts. Patients were transferred within a narrow age window (18.6 ± 1.0 age in years but at a wide range of times from the date of transplantation (5.1 ± 3.5 years and with a wide range of graft function (serum creatinine 182 ± 81 μmol/L. Conclusions The perception that pediatric transfers do poorly reflects advanced graft dysfunction in some at the time of transfer. The evidence also suggests that it is not the transfer of care that is the critical issue but rather recipients, somewhere between the ages of 11-14 and 25, are a unique and vulnerable cohort. Effective strategies to improve outcomes across this age group need to be identified and applied consistently.

Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney

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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.

Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

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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.

The Prophylactic Effect of Vitamin C on Oxidative Stress Indexes Following Exposure to Radio Frequency Wave Generated by a BTS Antenna Model in Rat Liver and Kidney

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Gholamali Jelodar

2014-02-01

Full Text Available Background: Radio frequency wave (RFW generated by base transceiver station (BTS has been reported to make deleterious effects on liver and kidney, possibly through oxidative stress. This study was conducted to evaluate the effect of radiofrequency wave (RFW-induced oxidative stress in the liver and kidney and the prophylactic effect of vitamin C on this organs by measuring the antioxidant enzymes activity including: glutathione peroxidase (GPx, superoxide dismutase (SOD and catalase (CAT, and malondialdehyde (MDA. Materials and Methods: In this experimental study, thirty-two adult male Sprague-Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: control, vitamin C (L-ascorbic acid 200 mg/kg of body weight/day by gavage, test (exposed to 900MHz RFW and the treated group (received vitamin C in addition to exposure to RFW. At the end of the experiment all animals were sacrificed and their liver and kidney were removed and were used for measurement of antioxidant enzymes and MDA activity. Results: The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (p<0.05. In the treated group vitamin C improved antioxidant enzymes activity and reduced MDA compared to the test group (p<0.05. Conclusion: It can be concluded that RFW causes oxidative stress in liver and kidney, and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Methylphenidate increases glucose uptake in the brain of young and adult rats.

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Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

2015-10-01

Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer.

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Alsaiari, Ahmed; Joury, Abdulaziz; Aljuaid, Mossab; Wazzan, Mohammed; Pines, Jesse M

2017-12-01

The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

Different Astrocytic Activation between Adult Gekko japonicus and Rats during Wound Healing In Vitro.

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Yun Gu

Full Text Available Glial scar formation is a major obstacle to regeneration after spinal cord injury. Moreover, it has been shown that the astrocytic response to injury differs between species. Gekko japonicas is a type of reptile and it shows differential glial activation compared to that of rats. The purpose of the present study was to compare the proliferation and migration of astrocytes in the spinal cords of geckos and rats after injury in vitro. Spinal cord homogenate stimulation and scratch wound models were used to induce astrocytic activation in adult and embryonic rats, as well as in adult geckos. Our results indicated that astrocytes from the adult rat were likely activated by mechanical stimulation, even though they showed lower proliferation abilities than the astrocytes from the gecko under normal conditions. Furthermore, a transcriptome analysis revealed that the differentially expressed genes in astrocytes from adult rats and those from geckos were enriched in pathways involved in proliferation and the response to stimuli. This implies that intrinsic discrepancies in gene expression patterns might contribute to the differential activation of astrocytes between species.

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

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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.

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

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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.

Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

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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.

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

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/.

Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs Protected Rats Against Acute Kidney Injury

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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.

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

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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

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.

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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.

Kidney (Renal Cell) Cancer—Patient Version

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Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

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.

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

Averting the Legacy of Kidney Disease—Focus on Childhood

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Julie R. Ingelfinger

2016-02-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. “For in every adult there dwells the child that was, and in every child there lies the adult that will be.”—John Connolly, The Book of Lost Things.

In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney.

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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.

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

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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.

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

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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

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

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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

Dietary modulation of parathion-induced neurotoxicity in adult and juvenile rats.

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Liu, Jing; Karanth, Subramanya; Pope, Carey

2005-06-01

Previous studies indicated that dietary glucose (15% in drinking water) could markedly exacerbate the toxicity of parathion in adult rats. The present study evaluated the effect of consumption of the commonly used sweetener, high fructose corn syrup (HFCS), on parathion toxicity in adult and juvenile rats. Animals were given free access to either water or 15% HFCS in drinking water for a total of 10 days and challenged with parathion (6 or 18 mg/kg, s.c., for juveniles or adults, respectively) on the 4th day. Signs of cholinergic toxicity, body weight and chow/fluid intake were recorded daily. Acetylcholinesterase (AChE) activity and immunoreactivity (AChE-IR) in frontal cortex and diaphragm were measured at 2, 4, and 7 days after parathion. As HFCS was associated with significant reduction in chow intake, adult rats were also pair-fed to evaluate the effect of similar reduced chow intake alone on parathion toxicity. The results indicated that the cholinergic toxicity of parathion was significantly increased by HFCS feeding in both age groups. The excess sugar consumption, however, did not significantly affect parathion-induced AChE inhibition in either tissue or either age group. Enzyme immunoreactivity in frontal cortex was generally not affected in either age group while diaphragm AChE-IR was significantly reduced by parathion and HFCS alone in adult animals at 2 and 4 days timepoints, and more so by the combination of sugar feeding and parathion exposure in both age groups. Food restriction alone did not exacerbate parathion toxicity. While the mechanism(s) remains unclear, we conclude that voluntary consumption of the common sweetener HFCS can markedly amplify parathion acute toxicity in both juvenile and adult rats.

Assessment of protective effects of methylprednisolone and pheniramine maleate on reperfusion injury in kidney after distant organ ischemia: a rat model.

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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

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

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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

Renal function in streptozotocin-diabetic rats

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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...

Glucocorticoid impairs growth of kidney outer medulla and accelerates loop of Henle differentiation and urinary concentrating capacity in rat kidney development

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Stubbe, Jane; Madsen, Kirsten; Nielsen, Finn Thomsen

2006-01-01

In the rat, urinary concentrating ability develops progressively during the third postnatal (P) week and nearly reaches adult level at weaning (P21) governed by a rise in circulating glucocorticoid. Elevated extracellular osmolality can lead to growth arrest of epithelial cells. We tested...

Kidney stone formation and antioxidant effects of Cynodon dactylon decoction in male Wistar rats.

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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.

Long-term organ culture of adult rat colon

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Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

1978-01-01

. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

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.

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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

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.

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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.

Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats.

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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.

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

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....

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

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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.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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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.

Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

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Sanchez-Criado Jose E

2004-09-01

Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

An observational study of health literacy and medication adherence in adult kidney transplant recipients.

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Demian, Maryam N; Shapiro, R Jean; Thornton, Wendy Loken

2016-12-01

There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (Δ R 2 = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence.

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

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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.

Selenium-75 and technetium-95m biokinetics in rats at different physiological states

International Nuclear Information System (INIS)

Archimbaud, Yves; Grillon, Gerard; Poncy, Jean-Luc; Masse, Roland

1992-06-01

Selenium 79 ( 79 Se) and technetium ( 99 Tc), beta emitters, components of nuclear wastes, may increase the dose equivalent to members of the public. Data used by ICRP show that there is relatively little information on Te and Se biokinetics at different physiologic stages. Retention was almost equivalent for young, male adult and pregnant rat. Selenium was concentrated in the testis, the kidneys, the liver and the spleen as technetium was in the skin, the thyroid and the kidneys. The biological half-time for Se and Te was respectively 20 and 41 days for pregnant rats, 33 and 15 days for young rats. Placental transfer per one fetus was 0.56% of the initial activity for Te and 1.27% for Se. These data point out the eventually high doses delivered to the skin for Te and to the testis for Se. They may be taken into consideration in estimating risk by humans at different stages of life [fr

Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

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Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

2006-09-01

Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

Effect of the aqueous extract of Foeniculum vulgare (fennel on the kidney in experimental PCOS female rats

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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

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

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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.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands

NARCIS (Netherlands)

Dobrowolski, Linn C; van Huis, Maike; van der Lee, Johanna H; Peters Sengers, Hessel; Liliën, Marc R; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H; de Fijter, Johan W; Berger, Stefan P; van Zuilen, Arjan; Nurmohamed, Shaikh A; Betjes, Michiel H G; Hilbrands, Luuk; Hoitsma, Andries J; Bemelman, Frederike J; Krediet, C T Paul; Groothoff, Jaap W

2016-01-01

INTRODUCTION: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the

Some behavioral aspects of adult rats irradiated prenatally

International Nuclear Information System (INIS)

Vekovishcheva, O.Yu.; Blagova, O.E.; Borovitskaya, A.E.; Evtushenko, V.I.; Khanson, K.P.

1992-01-01

This is a study of the effects of prenatal irradiation on the behavior of rats. The experiments were performed on 42 eighteen month old rats of both sexes. Eight of the males and thirteen females had been irradiated prenatally. The results of this experiment indicated that in general, the activation of behavior, the appearance of aggression and the increase in chaos along with the presence of behavior poses were typical of the suppressed condition of the prenatal irradiated animal. Also, among prenatally irradiated animals, there was a greater degree of anxiety, a slow rate of adjustment to unfamiliar situations and unfriendly relationships between animals of the same sex. These results were compared with the results of behavioral experiments on irradiated adult rats

Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study

OpenAIRE

ALKHEDAIDE, ADEL; SOLIMAN, MOHAMED MOHAMED; SALAH-ELDIN, ALAA-ELDIN; ISMAIL, TAMER AHMED; ALSHEHIRI, ZAFER SAAD; ATTIA, HOSSAM FOUAD

2016-01-01

The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca-Cola, Pepsi and 7-Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi-quantitat...

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy.

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Marin, Evelyn Cristina Santana; Balbi, Ana Paula Coelho; Francescato, Heloísa Della Coletta; Alves da Silva, Cleonice Giovanini; Costa, Roberto Silva; Coimbra, Terezila M

2008-01-01

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

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

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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

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

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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.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

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Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K; Kramer, Holly; Rosas, Sylvia E; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L

2016-01-01

Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

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Harini Sarathy

Full Text Available Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity.We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria.Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4% versus Mexican-Americans (40.6% or non-Hispanic whites (37.4% (P-value = 0.004. Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2, p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease.Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.

The effect of zinc on healing of renal damage in rats.

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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.

The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

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Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

2015-01-01

The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

Averting the legacy of kidney disease – focus on childhood

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Julie R. Ingelfinger

2016-03-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease: focus on childhood

Science.gov (United States)

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:28031959

Averting the legacy of kidney disease - focus on childhood

Directory of Open Access Journals (Sweden)

J.R. Ingelfinger

2016-01-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Community-acquired acute kidney injury in adults in Africa.

Science.gov (United States)

Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

EFFECTS OF EARLY POSTNATAL ANOXIA ON ADULT LEARNING AND EMOTION IN RATS

NARCIS (Netherlands)

BUWALDA, B; NYAKAS, C; VOSSELMAN, HJ; LUITEN, PGM; Vosselman, Henk Jan

Cognitive functioning, behavioural attention and anxiety were studied in adult male Wistar rats after early postnatal anoxia. Spatial memory performance in the holeboard learning task was impaired in anoxic rats when compared with control animals. Attention assessed by the behavioural immobility

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands

NARCIS (Netherlands)

Dobrowolski, Linn C.; van Huis, Maike; van der Lee, Johanna H.; Sengers, Hessel Peters; Lilien, Marc R.; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H.; de Fijter, Johan W.; Berger, Stefan P.; van Zuilen, Arjan; Nurmohamed, Shaikh A.; Betjes, Michiel H. G.; Hilbrands, Luuk; Hoitsma, Andries J.; Bemelman, Frederike J.; Krediet, Paul; Groothoff, Jaap W.

2016-01-01

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from

Turnover time of Leydig cells and other interstitial cells in testes of adult rats

NARCIS (Netherlands)

Teerds, K. J.; de rooij, D. G.; Rommerts, F. F.; van der Tweel, I.; Wensing, C. J.

1989-01-01

The aim of this study was to investigate the turnover of Leydig cells and other interstitial cells in the adult rat testis. Normal adult rats received injections of [3H]thymidine at 9:00 and 21:00 for 2, 5, or 8 days. The percentage of labeled Leydig cells, which was initially low (0.8% +/- 0.2%),

Impact of end-stage kidney disease on academic achievement and employment in young adults: a mixed methods study.

Science.gov (United States)

Murray, Peter D; Dobbels, Fabienne; Lonsdale, Daniel C; Harden, Paul N

2014-10-01

Young adult kidney patients are at an important stage of development when end-stage kidney disease (ESKD) may adversely influence progress in education and employment. This study is designed to assess the impact of ESKD on education and employment outcomes in young adults. This cross-sectional study was a mixed methods design. Education and career achievements in young adults with ESKD were recorded quantitatively using a questionnaire survey (n = 57): 14 of 57 representative participants were subsequently selected for semistructured interview. Questionnaire survey was conducted in 57 young adults (median age 25): 8.8% (n = 5) were predialysis; 14.0% (n = 8) dialysis; and 78.9% (n = 45) were kidney transplant recipients. Median school-leaving age was 16 (interquartile range = 15-19). Of 57 young adults, 10 (17.5%) were still studying, 43 (75.4%) had completed education, 34 (59.7%) were employed (23 full time and 11 part time), and 19 (33.3%) were unemployed. Twenty-seven of 45 transplanted patients were employed (60.0%). Of these 27, 21 were full time (77.8%). Five of eight dialysis patients were employed: only one of eight was full-time employed (12.5%). Themes impacting on education and employment included low energy levels, time missed, loss of self-esteem, and feelings of loneliness and isolation, which may progress to depression and recreational drug use. Lack of understanding from educators and employers resulting in lost work, and career ambitions changed or limited because of dialysis. Dialysis has a major negative impact on education and reduced employment rates of young adults. There is a general lack of understanding among educators and employers of the impact of ESKD. Low energy levels, lack of self-esteem, and depression are key factors. There is a need for health care providers to recognize this issue and invest in supporting young adults with ESKD. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights

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.

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

Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

International Nuclear Information System (INIS)

Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

2015-01-01

Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT 2 R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT 1a R)/AT 2 R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT 2 R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT 2 R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits

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...

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.

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.

MAGIC Study: Aims, Design and Methods using SystemCHANGE™ to Improve Immunosuppressive Medication Adherence in Adult Kidney Transplant Recipients.

Science.gov (United States)

Russell, Cynthia L; Moore, Shirley; Hathaway, Donna; Cheng, An-Lin; Chen, Guoqing; Goggin, Kathy

2016-07-16

Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed to enhance immunosuppressive medication adherence in adult non-adherent kidney transplant recipients from two transplant centers. Grounded in the Socio-Ecological Model, SystemCHANGE™ seeks to systematically improve medication adherence behaviors by identifying and shaping routines, involving supportive others in routines, and using medication taking feedback through small patient-led experiments to change and maintain behavior. After a 3-month screening phase of 190 eligible adult kidney transplant recipients, those who are adherent as measured by electronic monitoring, will be randomized into a 6-month SystemCHANGE™ intervention or attention-control phase, followed by a 6-month maintenance phase without intervention or attention. Differences in adherence between the two groups will be assessed at baseline, 6 months (intervention phase) and 12 months (maintenance phase). Adherence mediators (social support, systems-thinking) and moderators (ethnicity, perceived health) are examined. Patient outcomes (creatinine/blood urea nitrogen, infection, acute/chronic rejection, graft loss, death) and cost effectiveness are to be examined. Based on the large effect size of 1.4 found in our pilot study, intervention shows great promise

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

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol

International Nuclear Information System (INIS)

Salazar, Keith D.; Brinkerhoff, Christopher J.; Lee, Janice S.; Chiu, Weihsueh A.

2015-01-01

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPK models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose–response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. - Highlights: • We model two metabolically-related fuel oxygenates to address toxicity data gaps. • Kidney and liver effects are compared on an internal dose basis. • Noncancer kidney effects are consistent using TBA blood concentration. • Liver weight changes are consistent using TBA metabolic rate. • Kidney and liver tumors are not consistent using

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol

Energy Technology Data Exchange (ETDEWEB)

Salazar, Keith D., E-mail: Salazar.keith@epa.gov [Toxicity Pathways Branch, IRIS Division, NCEA, ORD, US EPA, Washington, DC 20460 (United States); Brinkerhoff, Christopher J., E-mail: Brinkerhoff.Chris@epa.gov [Risk Assessment Division, OPPT, OCSPP, US EPA, Washington, DC 20460 (United States); Lee, Janice S., E-mail: Lee.JaniceS@epa.gov [Toxicity Pathways Branch, IRIS Division, NCEA, ORD, US EPA, Washington, DC 20460 (United States); Chiu, Weihsueh A., E-mail: wchiu@cvm.tamu.edu [Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A& M University, College Station, TX 77843 (United States)

2015-11-01

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPK models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose–response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. - Highlights: • We model two metabolically-related fuel oxygenates to address toxicity data gaps. • Kidney and liver effects are compared on an internal dose basis. • Noncancer kidney effects are consistent using TBA blood concentration. • Liver weight changes are consistent using TBA metabolic rate. • Kidney and liver tumors are not consistent using

The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

Czech Academy of Sciences Publication Activity Database

Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

2017-01-01

Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

Effect of Consuming Iodized Salt on Fertility Indices in Male Adult Rats

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M. Mehrabani Natanzi

2017-06-01

Full Text Available Introduction: Today about 27.4 percent of female 15-44 years and 1 percent of female in fertility age are affected by infertility. Iodine is a rare element that is essential for the synthesis of thyroid hormones. Concentration of the thyroid hormones in blood under the influence of iodine intake and changes in thyroid hormones levels interact with reproductive system. Today, all the people of Iran consuming iodized salt regardless of iodine status in their body. In this study according to high prevalence of the infertility among young couples, iodized salt intake on fertility in male rats were investigated. Materials and Methods: In this study 20 male and 20 female adult Wistar rats were used. Twenty male adult Wistar rats were randomly divided into 2 groups. Including the control group and treatment group that received iodine and female adult Wistar were fed with a regular diet. Five male rats from each group were killed at the end of the fourth weeks in order to evaluate the possible effect of iodized salt on sperm analysis and weight of testis. After a month, male and female rats were placed in pairs in separate cages and their offspring were investigated in terms of number, gender and health. Results: The result of this study showed that the number of healthy offspring of treated male rats was significantly lower than the control group. Conclusion: Due to the negative effect of excessive iodine intake on fertility rate, it is recommended to couples to perform functional tests of their thyroid glands before intake of iodized salts.

A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

Science.gov (United States)

Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

2014-04-10

In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and hospitalization in older adults receiving hemodialysis.

Science.gov (United States)

Hall, Rasheeda K; Luciano, Alison; Pieper, Carl; Colón-Emeric, Cathleen S

2018-01-15

For older adults receiving dialysis, health-related quality of life is not often considered in prognostication of death or future hospitalizations. To determine if routine health-related quality of life measures may be useful for prognostication, the objective of this study is to determine the extent of association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse outcomes in older adults receiving dialysis. This is a longitudinal study of 3500 adults aged ≥75 years receiving dialysis in the United States in 2012 and 2013. We used Cox and Fine and Gray models to evaluate the association of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for sociodemographic variables, hemodialysis access type, laboratory values, and Charlson index. Three thousand one hundred thirty-two hemodialysis patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880 (28.1%) died and 2023 (64.6%) had at least one hospitalization over a median follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical component summary (PCS) in the lowest quintile had an increased adjusted risk of death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in the highest quintile. Cohort members with a SF-12 mental component summary in the lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17-1.65) compared with those in the highest quintile. In adjusted analyses, there was no association between the symptoms of kidney disease, effects of kidney disease, and burden of kidney disease subscales with time to death or first hospitalization. Competing risk models showed similar HRs. Among the KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with both death and future hospitalizations in older adults receiving hemodialysis Further research is needed to assess the value this subscale may add

Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.

Science.gov (United States)

Madsen, Heather B; Zbukvic, Isabel C; Luikinga, Sophia J; Lawrence, Andrew J; Kim, Jee Hyun

2017-09-01

Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypertension after kidney transplantation

NARCIS (Netherlands)

Dobrowolski, L.C.

2016-01-01

Hypertension increases the cardiovascular risk in kidney transplant recipients (KTRs). In chapter 2 we found that hypertension was highly prevalent in adult (77.2%), paediatric (62.7%) and young adult (86.4%) KTRs. Transition from the paediatric to adult care did not affect hypertension and there

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

Science.gov (United States)

Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

2017-11-01

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

Science.gov (United States)

Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

2012-08-01

Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

Effects of 1 alpha,25-Dihydroxyvitamin D-3 on Transporters and Enzymes of the Rat Intestine and Kidney In Vivo

NARCIS (Netherlands)

Chow, Edwin C. Y.; Sun, Huadong; Khan, Ansar A.; Groothuis, Geny M. M.; Pang, K. Sandy

1 alpha,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3), the natural ligand of the vitamin D receptor (VDR), was found to regulate bile acid related transporters and enzymes directly and indirectly in the rat intestine and liver in vivo. The kidney is another VDR-rich target organ in which VDR regulation

[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.

Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

Directory of Open Access Journals (Sweden)

Ryan W Speir

Full Text Available Renal ischemia-reperfusion (IR causes acute kidney injury (AKI with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group received Valproic Acid (150 mg/kg; VPA, Dexamethasone (3 mg/kg; Dex or Vehicle (saline intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL at 24 h was reduced (P<0.05 in VPA (2.7±1.8 and Dex (2.3±1.2 compared to Vehicle (3.8±0.5 group. At 3 h, urine albumin (mg/mL was higher in Vehicle (1.47±0.10, VPA (0.84±0.62 and Dex (1.04±0.73 compared to naïve (uninjured/untreated control (0.14±0.26 group. At 24 h post-IR urine lipocalin-2 (μg/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (9.61-11.36 compared to naïve group (0.67±0.29; also, kidney injury molecule-1 (KIM-1; ng/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (13.7-18.7 compared to naïve group (1.7±1.9. Histopathology demonstrated reduced (P<0.05 ischemic injury in the renal cortex in VPA (Grade 1.6±1.5 compared to Vehicle (Grade 2.9±1.1. Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.

Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

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Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

2010-03-01

Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

Science.gov (United States)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

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

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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.

Histological changes in the cerebelli of adult wistar rats exposed to ...

African Journals Online (AJOL)

The different constituents of tobacco smoke have been linked to different diseased conditions. In this work, the histological effects of cigarette smoke on the cerebellum of adult male Wistar rats were studied. Sixteen Wistar rats with mean weight of 153.24 ± 4.12 g were grouped equally into four. The Control Group A was ...

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

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