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Sample records for rat kidney mitochondria

  1. 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

  2. Respiration and phosphorylation in liver and kidney mitochondria of rats exposed to high-energy gamma and beta radiation

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    Mokhoreva, S I; Vetlugina, N S

    1973-01-01

    The effect of whole-body irradiation with ..gamma.. rays (radiation source /sup 60/Co) at 40 rad and ..beta.. rays (source, a linear accelerator, electron energy 25 MeV) at 43 rad on oxidative phosphorylation in liver and kidney mitochondria was studied in rats. Gamma radiation gradually slowed the esterification of phosphate and respiratory rate during the oxidation of succinate in the liver and kidney mitochondria. The decrease was largest on day 15 after irradiation. However, the P/O ratio did not decrease by more than 10 to 12 percent. Despite the oxidation of glutamate in the mitochondria, respiration, phosphate consumption, and P/O ratio scarcely changed. Irradiation with electrons slowed the rate of oxidation of succinate and glutamate in liver mitochondria within 3 to 7 days. Phosphate consumption decreased at the same time so that the P/O ratio remained unchanged. Beta irradiation had virtually no effect on liver mitochondria. There is a discussion of the mechanism of action of high-energy radiation on the phosphorylation system of the mitochondria.

  3. Regulation of valine and. alpha. -ketoisocaproate metabolism in rat kidney mitochondria

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    Miller, R.H.; Harper, A.E. (Univ. of Wisconsin, Madison (USA))

    1988-10-01

    Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and {alpha}-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids {alpha}-ketoisocaproate (KIC) or {alpha}-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of {sup 14}C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, {alpha}-ketoglutarate ({alpha}-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM {alpha}-KG as the amino acceptor; these rates were 5- to 50-fold those without added {alpha}-KG. Rates of CO{sub 2} evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO{sub 2} evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, {alpha}-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD.

  4. Regulation of valine and α-ketoisocaproate metabolism in rat kidney mitochondria

    International Nuclear Information System (INIS)

    Miller, R.H.; Harper, A.E.

    1988-01-01

    Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and α-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids α-ketoisocaproate (KIC) or α-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of 14 C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, α-ketoglutarate (α-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM α-KG as the amino acceptor; these rates were 5- to 50-fold those without added α-KG. Rates of CO 2 evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO 2 evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, α-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD

  5. Isolation of rat adrenocortical mitochondria

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    Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  6. Avocado oil induces long-term alleviation of oxidative damage in kidney mitochondria from type 2 diabetic rats by improving glutathione status.

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    Ortiz-Avila, Omar; Figueroa-García, María Del Consuelo; García-Berumen, Claudia Isabel; Calderón-Cortés, Elizabeth; Mejía-Barajas, Jorge A; Rodriguez-Orozco, Alain R; Mejía-Zepeda, Ricardo; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2017-04-01

    Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.

  7. Action of diclofenac on kidney mitochondria and cells

    International Nuclear Information System (INIS)

    Ng, Lin Eng; Vincent, Annette S.; Halliwell, Barry; Wong, Kim Ping

    2006-01-01

    The mitochondrial membrane potential measured in isolated rat kidney mitochondria and in digitonin-permeabilized MDCK type II cells pre-energized with succinate, glutamate, and/or malate was reduced by micromolar diclofenac dose-dependently. However, ATP biosynthesis from glutamate/malate was significantly more compromised compared to that from succinate. Inhibition of the malate-aspartate shuttle by diclofenac with a resultant decrease in the ability of mitochondria to generate NAD(P)H was demonstrated. Diclofenac however had no effect on the activities of NADH dehydrogenase, glutamate dehydrogenase, and malate dehydrogenase. In conclusion, decreased NAD(P)H production due to an inhibition of the entry of malate and glutamate via the malate-aspartate shuttle explained the more pronounced decreased rate of ATP biosynthesis from glutamate and malate by diclofenac. This drug, therefore affects the bioavailability of two major respiratory complex I substrates which would normally contribute substantially to supplying the reducing equivalents for mitochondrial electron transport for generation of ATP in the renal cell

  8. Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.

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    Schiffer, Tomas A; Gustafsson, Håkan; Palm, Fredrik

    2018-05-30

    The kidneys receive approximately 25% of cardiac output, which is a prerequisite in order to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is relating to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation in order to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla functions at the verge of hypoxia and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats were estimated using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

  9. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

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    Denis N Silachev

    Full Text Available BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. METHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated

  10. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

    Science.gov (United States)

    Silachev, Denis N; Isaev, Nikolay K; Pevzner, Irina B; Zorova, Ljubava D; Stelmashook, Elena V; Novikova, Svetlana V; Plotnikov, Egor Y; Skulachev, Vladimir P; Zorov, Dmitry B

    2012-01-01

    Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced

  11. Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

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    Ortiz-Avila, Omar; Sámano-García, Carlos Alberto; Calderón-Cortés, Elizabeth; Pérez-Hernández, Ismael H; Mejía-Zepeda, Ricardo; Rodríguez-Orozco, Alain R; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2013-06-01

    Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

  12. Transport of N-acetylglutamate in rat-liver mitochondria

    NARCIS (Netherlands)

    Meijer, A. J.; van Woerkom, G. M.; Wanders, R. J.; Lof, C.

    1982-01-01

    The permeability properties of the rat-liver mitochondrial membrane for N-acetylglutamate, the activator of carbamoyl-phosphate synthetase (ammonia), were studied. 1. Transport of N-acetylglutamate into the mitochondria was only observed in partially or fully de-energized mitochondria and when the

  13. The three-kidney rat

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

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

    1987-08-01

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

  15. Endurance training increases the efficiency of rat skeletal muscle mitochondria.

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    Zoladz, Jerzy A; Koziel, Agnieszka; Woyda-Ploszczyca, Andrzej; Celichowski, Jan; Jarmuszkiewicz, Wieslawa

    2016-10-01

    Endurance training enhances mitochondrial oxidative capacity, but its effect on mitochondria functioning is poorly understood. In the present study, the influence of an 8-week endurance training on the bioenergetic functioning of rat skeletal muscle mitochondria under different assay temperatures (25, 35, and 42 °C) was investigated. The study was performed on 24 adult 4-month-old male Wistar rats, which were randomly assigned to either a treadmill training group (n = 12) or a sedentary control group (n = 12). In skeletal muscles, endurance training stimulated mitochondrial biogenesis and oxidative capacity. In isolated mitochondria, endurance training increased the phosphorylation rate and elevated levels of coenzyme Q. Moreover, a decrease in mitochondrial uncoupling, including uncoupling protein-mediated proton leak, was observed after training, which could explain the increased reactive oxygen species production (in nonphosphorylating mitochondria) and enhanced oxidative phosphorylation efficiency. At all studied temperatures, endurance training significantly augmented H2O2 production (and coenzyme Q reduction level) in nonphosphorylating mitochondria and decreased H2O2 production (and coenzyme Q reduction level) in phosphorylating mitochondria. Endurance training magnified the hyperthermia-induced increase in oxidative capacity and attenuated the hyperthermia-induced decline in oxidative phosphorylation efficiency and reactive oxygen species formation of nonphosphorylating mitochondria via proton leak enhancement. Thus, endurance training induces both quantitative and qualitative changes in muscle mitochondria that are important for cell signaling as well as for maintaining muscle energy homeostasis, especially at high temperatures.

  16. Membrane potential of mitochondria from the liver of irradiated rats

    International Nuclear Information System (INIS)

    Fomenko, B.S.; Kaminin, A.N.; Elfimova, I.A.; Akoev, I.G.

    1977-01-01

    Measurements of the membrane potential of rat liver mitochondria 1 hour after irradiation with 800 R dose showed a decrease of its value. The potential decreased against the background of the activation of the generating mechanisms (the electron transport chain and ATP-ases). During energization of the membranes by the electron transport chain similar effect has been observed with different oxidation substrates (NAD linked substrates and succinate). It suggests that similar causative factors are at the basis of the changes observed. It is quite possible that the increase in the rate of both mitochondria respiration and ATP hydrolysis after the irradiation of animals was a consequence of the radiation-induced decrease in the potential value. (author)

  17. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

    Directory of Open Access Journals (Sweden)

    Kentaro Takakura

    2017-11-01

    Full Text Available The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM, which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS, heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life

  18. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions.

    Science.gov (United States)

    Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

    2017-11-01

    The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS), heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life extension of these

  19. Mitochondria As the Target for the Modulatory Effect of Curcumin in Oxaliplatin-induced Toxicity in Isolated Rat Liver Mitochondria.

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    Waseem, Mohammad; Parvez, Suhel; Tabassum, Heena

    2017-01-01

    To explore hepatoprotective action of curcumin (CMN, a bioflavonoid) on oxaliplatin (Oxa)-triggered mitochondrial oxidative stress and respiratory chain complexes in liver of rats. Oxa is a ubiquitously utilized platinum-based chemotherapeutic agent commonly used for the treatment of colorectal cancer. Mitochondria have recently emerged as targets for anticancer drugs in several kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. There is a dearth of evidence involving the role of mitochondria in mediating Oxa-evoked hepatotoxicity and its underlying mechanism is still debatable. The study was performed in mitochondria isolated from liver of Wistar rats. Oxa (200 μg/mL) and CMN (5 μmol) were incubated under in vitro conditions. Oxa evoked a significant increase in the membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, decrease in reduced glutathione (GSH) and nonprotein thiol (NP-SH) levels. Oxa also caused a marked decline in the activities of enzymatic antioxidants and respiratory chain enzymes (I, II, III and V) in liver mitochondria. CMN pre-treatment significantly prevented the activities of enzymatic antioxidants and mitochondrial respiratory chain enzymes. CMN also restored the LPO and PC contents, GSH and NP-SH levels in liver mitochondria. CMN intake might be effective in regulation of Oxa-evoked mitotoxicity during chemotherapy. Moreover, it is included in the armamentarium for anticancer agent-induced oxidative stress. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  20. Effect of heavy water on isolated rat liver mitochondria

    International Nuclear Information System (INIS)

    Huebner, G.

    1981-01-01

    The rate of O 2 consumption by isolated rat liver mitochondria was determined polarographically with a Clark electrode at 25 0 C in the active (state 3), strongly coupled (state 4) and decoupled state of the mitochondria in media containing H 2 16 O, D 2 16 O or H 2 18 O. The results confirm the value of the D 2 O isotope effect in the form on an O 2 -consumption inhibition. In H 2 18 O no isotope effect has been detected in the state of controlled respiration. In contrast, a strongly marked inverse isotope effect has been found in the active state after ADP addition and in the decoupled state after DNP addition. This inverse isotope effect occurs in reactions involving a preceding equilibrium. According to the chemiosmotic hypothesis of oxidative phosphorylation the formation of hydronium ions is part of this reaction. The equilibrium constant k 2 = 0.9774 for the hydronium ion in H 2 16 O and H 2 18 O implies that the formation of the hydronium ion in H 2 18 O is preferred to that in H 2 16 O. The high inverse H 2 18 O isotope effect respiration shows that the formation of H 3 O + contributes to the vectorial proton transport, probably as a preceding equilibrium, and that in the active state of the respiratory chain this reaction may be the rate-determining step. (author)

  1. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

    Energy Technology Data Exchange (ETDEWEB)

    Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

    2009-01-15

    One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

  2. 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

  3. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

  4. Mitochondria morphologic changes and metabolic effects of rat hippocampus after microwave irradiation

    International Nuclear Information System (INIS)

    Zhao Li; Peng Ruiyun; Gao Yabing; Wang Shuiming; Wang Lifeng; Dong Qi; Xu Xinping; Ma Junjie

    2007-01-01

    Objective: To investigate the effect of microwave on mitochondria morphologic and metabolism of rat hippocampus. Methods: 30 male rats were exposed to microwave with the average power density of 30 mW/cm 2 . Rats were sacrificed at 6 h, 1 d, 3 d and 7 d after irradiation. Electron microscope, enzymatic activity staining and spectrophotometer were used to study ultrastructure change of hippocampus mitochondria and activity of ATPase, SDH and MAO. Mitochondrial ATP, ADP and AMP contents were measured by high performance liquid chromatography (HPLC). Results: At 6 h after microwave radiation, the sizes and shapes of hippocampus mitochondria were abnormal and the injury of mitochondria was aggravated at 1 and 3 d after radiation. The mitochondria presented swell, cavitation including disorder, shortness and decrease of crest. The activity of SDH and content of ATP were decreased at 6 h, most serious at 3 d(P<0.01), and recovered at 7 d after radiation. The activity of ATPase and MAO increased notably at 1 d and 3 d after radiation (P<0.01). Conclusions: Microwave can damage the structure and function of mitochondria in rat hippocampus, and cause the energy metabolism of enzyme disorder. (authors)

  5. Effect of sclerin on amino acid incorporation into mitochondria isolated from rat liver

    International Nuclear Information System (INIS)

    Yamaguchi, Masanori; Satomura, Yukio

    1975-01-01

    Though sclerin (SCL) stimulated amino acid incorporation into the protein fraction of post mitochondrial supernatant of rat liver homogenate, it had no effect on the incorporation into the isolated mitochondria at pH 7.2, despite of its stimulating effect on mitochondrial oxidative phosphorylation. SCL stimulated amino acid incorporation into the mitochondria at pH 6.1, and to some extent maintained the activity on that in mitochondria during aging in hypotonic Tris-HCl buffer (pH 7.2). Since SCL prevented leakage of amino acids from the mitochondria into these buffers, it was suggested that SCL may protect a structure of mitochondrial membrane which appeared to have a significance on transport of amino acids. In liver slices, SCL stimulated amino acid incorporation only into the extra-mitochondrial fraction for the first 3 min, but gradually turned to simulate incorporation into mitochondria within 30 min. (auth.)

  6. Effect of sclerin on amino acid incorporation into mitochondria isolated from rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, M; Satomura, Y [Osaka City Univ. (Japan). Faculty of Science

    1975-08-01

    Though sclerin (SCL) stimulated amino acid incorporation into the protein fraction of post mitochondrial supernatant of rat liver homogenate, it had no effect on the incorporation into the isolated mitochondria at pH 7.2, despite of its stimulating effect on mitochondrial oxidative phosphorylation. SCL stimulated amino acid incorporation into the mitochondria at pH 6.1, and to some extent maintained the activity on that in mitochondria during aging in hypotonic Tris-HCl buffer (pH 7.2). Since SCL prevented leakage of amino acids from the mitochondria into these buffers, it was suggested that SCL may protect a structure of mitochondrial membrane which appeared to have a significance on transport of amino acids. In liver slices, SCL stimulated amino acid incorporation only into the extra-mitochondrial fraction for the first 3 min, but gradually turned to simulate incorporation into mitochondria within 30 min.

  7. Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide.

    Science.gov (United States)

    Gao, Xin; Zheng, Chun Yan; Yang, Ling; Tang, Xi Can; Zhang, Hai Yan

    2009-06-01

    Our previous work in cells and animals showed that mitochondria are involved in the neuroprotective effect of huperzine A (HupA). In this study, the effects of HupA on isolated rat brain mitochondria were investigated. In addition to inhibiting the Abeta(25-35) (40 microM)-induced decrease in mitochondrial respiration, adenosine 5'-triphosphate (ATP) synthesis, enzyme activity, and transmembrane potential, HupA (0.01 or 0.1 microM) effectively prevented Abeta-induced mitochondrial swelling, reactive oxygen species increase, and cytochrome c release. More interestingly, administration of HupA to isolated mitochondria promoted the rate of ATP production and blocked mitochondrial swelling caused by normal osmosis. These results indicate that HupA protects mitochondria against Abeta at least in part by preserving membrane integrity and improving energy metabolism. These direct effects on mitochondria further extend the noncholinergic functions of HupA.

  8. 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.

  9. Radioprotective effects of Asparagus racemosus extracts against free radical damage in rat liver mitochondria

    International Nuclear Information System (INIS)

    Boloor, K.K.; Kamat, J.P.; Devasagayam, T.P.A.; Venkatachalam, S.R.

    2000-01-01

    The possible antioxidant effect of the extracts of Asparagus racemosus against membrane damage induced by free radicals generated during γ-radiation was examined in rat liver/brain mitochondria. These extracts displayed significant antioxidant properties in mitochondria against oxidation of both lipids and proteins as assessed by lipid peroxidation, protein oxidation and depletion of thiols. The inhibitory effect of the extracts, rich in polysaccharides like galactose, was more than that of the established antioxidants glutathione and ascorbic acid. (author)

  10. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    Directory of Open Access Journals (Sweden)

    Halina Baran*

    2016-01-01

    Full Text Available Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3, respiratory control index (RC and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM or succinate (10 mM and in the presence of L-tryptophan metabolites (1 mM or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver

  11. Mitochondria from rat uterine smooth muscle possess ATP-sensitive potassium channel

    Directory of Open Access Journals (Sweden)

    Olga B. Vadzyuk

    2018-03-01

    Full Text Available The objective of this study was to detect ATP-sensitive K+ uptake in rat uterine smooth muscle mitochondria and to determine possible effects of its activation on mitochondrial physiology. By means of fluorescent technique with usage of K+-sensitive fluorescent probe PBFI (potassium-binding benzofuran isophthalate we showed that accumulation of K ions in isolated mitochondria from rat myometrium is sensitive to effectors of KATP-channel (ATP-sensitive K+-channel – ATP, diazoxide, glibenclamide and 5HD (5-hydroxydecanoate. Our data demonstrates that K+ uptake in isolated myometrium mitochondria results in a slight decrease in membrane potential, enhancement of generation of ROS (reactive oxygen species and mitochondrial swelling. Particularly, the addition of ATP into incubation medium led to a decrease in mitochondrial swelling and ROS production, and an increase in membrane potential. These effects were eliminated by diazoxide. If blockers of KATP-channel were added along with diazoxide, the effects of diazoxide were removed. So, we postulate the existence of KATP-channels in rat uterus mitochondria and assume that their functioning may regulate physiological conditions of mitochondria, such as matrix volume, ROS generation and polarization of mitochondrial membrane. Keywords: ATP-sensitive potassium channel, Diazoxide, 5-hydroxydecanoate, Myometrium, Mitochondria, Mitochondrial swelling, Mitochondrial membrane potential, ROS

  12. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. EFFECT OF ACTIVE ACCUMULATION OF CALCIUM AND PHOSPHATE IONS ON THE STRUCTURE OF RAT LIVER MITOCHONDRIA

    Science.gov (United States)

    Greenawalt, John W.; Rossi, Carlo S.; Lehninger, Albert L.

    1964-01-01

    Rat liver mitochondria allowed to accumulate maximal amounts of Ca++ and HPO4 = ions from the suspending medium in vitro during respiration have a considerably higher specific gravity than normal mitochondria and may be easily separated from the latter by isopycnic centrifugation in density gradients of sucrose or cesium chloride. When the mitochondria are allowed to accumulate less than maximal amounts of Ca++ and HPO4 = from the medium, they have intermediate specific gravities which are roughly proportional to their content of calcium phosphate. Maximally "loaded" mitochondria are relatively homogeneous with respect to specific gravity. Correlated biochemical and electron microscopic studies show that Ca++-loaded mitochondria contain numerous dense granules, of which some 85 per cent are over 500 A in diameter. These granules are electron-opaque not only following fixation and staining with heavy metal reagents, but also following fixation with formaldehyde, demonstrating that the characteristic granules in Ca++-loaded mitochondria have intrinsic electron-opacity. The dense granules are almost always located within the inner compartment of the mitochondria and not in the space between the inner and outer membranes. They are frequently located at or near the cristae and they often show electron-transparent "cores." Such granules appear to be made up of clusters of smaller dense particles, but preliminary x-ray diffraction analysis and electron diffraction studies have revealed no evidence of crystallinity in the deposits. The electron-opaque granules decrease in number when the Ca++-loaded mitochondria are incubated with 2,4-dinitrophenol; simultaneously there is discharge of Ca++ and phosphate from the mitochondria into the medium. PMID:14228516

  14. [ATP-synthetase activity, respiration and cytochromes of rat heart mitochondria in aging and hyperthyroidism].

    Science.gov (United States)

    Lemeshko, V V; Kaliman, P A; Belostotskaia, L I; Uchitel', A A

    1982-04-01

    The ATP-synthetase activity, the rate of oxygen uptake under different metabolic conditions, the tightness of coupling of respiration to oxidative phosphorylation and the cytochrome contents in heart mitochondria of rats from different age groups were studied under normal conditions and in hyperthyroidism. It was found that heart mitochondria of aged animals did not practically differ in terms of their functional activity from those of the young animals. Administration of thyroxin to the animals from all age groups produced no significant effects on the state of mitochondria, increasing the rate of ATP synthesis on alpha-glycerophosphate, which was especially well-pronounced in aged animals, and the cytochrome content in 1-month-old rats.

  15. Ketogenesis in rat-liver mitochondria: Stimulation by palmityl-coenzyme A

    NARCIS (Netherlands)

    Vaartjes, W.J.; Lopes-Cardozo, M.; Bergh, S.G. van den

    1972-01-01

    It is well-known that the movement of adenine nucleotides (AdN) across the inner mitochondrial membrane is markedly decreased both by unsaturated and by saturated long-chain fatty acids. A similar effect is displayed by palmityl-CoA as demonstrated recently with isolated mitochondria of rat

  16. The influence of dietary iodine and enviromental temperature on the activity of mitochondria in liver and kidney.

    Science.gov (United States)

    Chaiyabutr, N; Jakobsen, P E

    1978-08-01

    It was found that both effect of temperatures and diets influence metabolic changes in rabbits. In animals fed basal and PTU diets (propyl-thiouracil diets) at 34 degrees C for 4 weeks the metabolic response showed a marked reduction in feed intake and body weight, compared with animals fed at normal temperatures. In the animals fed the iodine diet, there was an increase in daily food consumption and weekly body weight gain at 34 degrees C. This indicates a rise in metabolic activity in this case. Studying the activity of kidney mitochondria of the three groups of animals using succinate as a substrate revealed that the P/O ratio tends to decrease in animals kept at 6 degrees C while the RCR value was not altered by changing conditions or produced by the different diets. At the temperature of 6 degrees C both the P/O ratios and the RCR values of liver mitochondria using succinate as a substrate decreased in the group of rabbits fed the basal and iodine diets, but were not significantly different in the group fed the PTU diet. In the experiment on kidney mitochondrial activity using alpha-ketoglutarate as a substrate it was found that both the P/O ratios and the RCR values from animals fed basal and PTU diets at 6 degrees C decreased slightly as compared with animals fed at 20 degrees C and 34 degrees C. In liver mitochondria, using alpha-ketoglutarate as a substrate a significant decrease in the P/O ratio and the RCR value was found for both rabbits fed the basal and the iodine diets at 6 degrees C. In the group of rabbits fed the PTU diet, the P/O ratio also decreased but the fall was not significant. These results suggested that the activity of succinate dehydrogenase in liver mitochondria increases in animals fed basal and iodine diets at 6 degrees C. The enzyme dehydrogenase involved in oxidation of alpha-ketoglutarate which is localized in the outer membrane of mitochondria seems to be affected by different temperatures and diets as compared with succinate

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  18. Binding of in vivo administrated 125-I-triiodothyronine by the rat liver mitochondria

    International Nuclear Information System (INIS)

    Fiedorowicz, K.; Nauman, A.; Nauman, J.

    1979-01-01

    In vivo administrated 125 I-triiodothyronine ( 125 I-T 3 ) was bound by the rat liver mitochondria. About 10 % of hormone was bound with external mitochondrial membrane while the remaining part with matrix and inner mitochondrial membrane. The highest accumulation of 125 I-T 3 in mitochondria was observed 30 min after injection while in the whole liver homogenate the highest hormone accumulation appeared 15 min post injection. Mitochondrial binding sites have a great capacity for T 3 which makes impossible estimation of the kinetic parameters of triiodothyronine-mitochondrium interaction by means of saturation and displacement of 125 I-T 3 . (author)

  19. Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen-N-acetyl cysteine-thioester (F-NAC) and fenbufen...... and fenbufen show any protective effect on fenbufen mediated inhibition of oxidative phosphorylation. Inclusion of NADPH in mitochondrial preparations with fenbufen did not modulate the inhibitory effects, suggesting no role of CYP mediated oxidative metabolites on the ATP synthesis in isolated mitochondria...

  20. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

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

    Science.gov (United States)

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

    1976-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Akira Marine

    2014-01-01

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

  3. Phospholipase activity in rat liver mitochondria studied by the use of endogenous substrates.

    Science.gov (United States)

    Bjornstad, P

    1966-09-01

    The hydrolysis of endogenous phosphatidyl ethanolamine and lecithin in rat liver mitochondria has been studied by using mitochondria from rats injected with ethanolamine-1,2-(14)C or choline-1,2-(14)C. A phospholipase A-like enzyme has been demonstrated, which catalyzes the hydrolysis of one fatty acid ester linkage in phosphatidyl ethanolamine and lecithin. Phosphatidyl ethanolamine is hydrolyzed in preference to lecithin and the main reaction products are free fatty acids and lysophosphatidyl ethanolamine. The further breakdown of lysophospholipids appears to be limited in mitochondria, which indicates that lysophospholipase activity is mainly located extramitochondrially. The enzymic system is greatly stimulated by calcium ions, and also slightly by magnesium ions, while EDTA inhibits it almost completely. These findings are discussed in relation to previous observations on the effect of calcium and of EDTA on the functions of mitochondria. The possible function of the mitochondrial phospholipase for the formation of phospholipids with special fatty acids at the alpha- and -position is discussed.

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

    International Nuclear Information System (INIS)

    Hayashi, M.; Katz, A.I.

    1987-01-01

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

  5. Effect of irradiation and of cysteamine on rat liver mitochondria

    International Nuclear Information System (INIS)

    Braquet, Monique.

    1979-06-01

    The aim of this work was to determine: the effects of a cobalt 60 gamma irradiation received by an animal, the biological repercussions of the preliminary administration of cysteamine to the animal exposed. To this end the amount of damage caused by in vivo irradiation of rats was estimated at three levels: on the whole body; on an important organ, the liver; on a specific organite, the mitochondrion. The methods of investigation used fall mainly within the province of biochemical technology. Studies on the effects of ionizing radiations on rats irradiated for ten days at 900 roentgens showed a generalized attack on the whole system, known as the ''Acute Irradiation Syndrome'' and divisible into three phases: stage one, initial phase involving loss of weight and destruction of the liver. These symptoms appear early and reach a paroxysm on the 4th day after irradiation. Stage two, remission phase (from the 5th to the 8th day) when the weight variations become stabilised. Stage three, last phase, often leading to the death between the 9th and 10th days. During the same 10-day period, on the same irradiated rats, the changes in enzymatic systems were followed in order to estimate the magnitude of peroxidative phenomena within a subcellular particle such as the mitochondrion. The results obtained prove a strong disorganisation of the mitochondrial function [fr

  6. 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 ...

  7. Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

    Science.gov (United States)

    Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

    2013-12-01

    Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

  8. Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

    Science.gov (United States)

    Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

    2015-11-01

    Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  9. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    Directory of Open Access Journals (Sweden)

    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  10. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  11. Changes in calcium uptake rate by rat cardiac mitochondria during postnatal development.

    Science.gov (United States)

    Bassani, R A; Fagian, M M; Bassani, J W; Vercesi, A E

    1998-10-01

    Ca2+ uptake, transmembrane electrical potential (Deltapsim) and oxygen consumption were measured in isolated ventricular mitochondria of rats from 3 days to 5 months of age. Estimated values of ruthenium red-sensitive, succinate-supported maximal rate of Ca2+ uptake (Vmax, expressed as nmol Ca2+/min/mg protein) were higher in neonates and gradually fell during postnatal development (from 435+/-24 at 3-6 days, to 156+/-10 in adults,Palpha-ketoglutarate as substrates) and state 3ADP (alpha-ketoglutarate-supported) respiration rates, as well as Deltapsim values (approximately-150 mV). Respiration-independent Deltapsim and Ca2+ uptake, supported by valinomycin-induced K+ efflux were also investigated at these ages. A transient Deltapsim (approximately -30 mV) was evoked by valinomycin in both neonatal and adult mitochondria. Respiration-independent Ca2+ uptake was also transient, but its initial rate was significantly higher in neonates than in adults (49. 4+/-10.0v 28.0+/-5.7 mmol Ca2+/min/mg protein,P<0.01). These results indicate that Ca2+ uptake capacity of rat cardiac mitochondria is remarkably high just after birth and declines over the first weeks of postnatal life, without change in apparent affinity of the transporter. Increased mitochondrial Ca2+ uptake rate in neonates appears to be related to the uniporter itself, rather than to modification of the driving force of the transport. Copyright 1998 Academic Press

  12. Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

    Directory of Open Access Journals (Sweden)

    T. RODRIGUES

    2009-01-01

    Full Text Available

    Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

  13. Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

    Science.gov (United States)

    Fattoretti, P; Bertoni-Freddari, C; Caselli, U; Paoloni, R; Meier-Ruge, W

    1998-03-16

    The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

  14. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

    Science.gov (United States)

    Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2017-07-01

    In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. 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 ...

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  17. 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

  18. Autophagic clearance of mitochondria in the kidney copes with metabolic acidosis.

    Science.gov (United States)

    Namba, Tomoko; Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi; Yamamoto, Takeshi; Matsuda, Jun; Kitamura, Harumi; Niimura, Fumio; Matsusaka, Taiji; Iwatani, Hirotsugu; Matsui, Isao; Kaimori, Junya; Kioka, Hidetaka; Isaka, Yoshitaka; Rakugi, Hiromi

    2014-10-01

    Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH4Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule-specific autophagy-deficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3-tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy. Copyright

  19. Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

    Directory of Open Access Journals (Sweden)

    Ivana Kancirová

    2016-06-01

    Full Text Available Objective(s: Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro or administered per os to rat (in vivo on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P

  20. Effects of exercise training and exhaustion on 45Ca uptake by rat skeletal muscle mitochondria and sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Bonner, H.W.; Leslie, S.W.; Combs, A.B.; Tate, C.A.

    1976-01-01

    Mitochondrial and sarcoplasmic reticular 45 Ca 2+ uptake and Ca 2+ -ATPase activity were determined in skeletal muscle from exercise trained and non-trained rats at rest or following short-term exhaustive exercise. In trained rats exercised to exhaustion, mitochondrial 45 Ca 2+ uptake was significantly depressed when compared to non-trained rats at rest. Ca 2+ -ATPase activity of sarcoplasmic reticulum from trained rats exercised to exhaustion was significantly increased as compared to trained rats at rest. These data suggest that the disruptive influence of Ca 2+ accumulation in mitochondria isolated following exhaustive exercise may be diminished as a result of training

  1. The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

    International Nuclear Information System (INIS)

    Kim, M.J.C.

    1988-01-01

    The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T 4 levels and T 4 treatment increased serum T 3 levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T 4 , the transition temperature disappeared due to a decoupling of succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T 4 treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca ++ Mg ++ ATPase and Mg ++ ATPase. T 4 treatment had potentiated this effect. T 4 increased the malate-aspartate shuttle and α-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-[ 14 C-U]/[6- 3 H]-glucose and gluconeogeneis from L-[ 14 C-U]-alanine was examined. Dietary fat or T 4 did not affect the glucose mass. T 4 increased the irreversible fractional glucose turnover rate

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

    Science.gov (United States)

    Yoldas, Atilla; Dayan, Mustafa Orhun

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  4. The Swelling of Rat Liver Mitochondria by Thyroxine and its Reversal

    Science.gov (United States)

    Lehninger, Albert L.; Ray, Betty Lou; Schneider, Marion

    1959-01-01

    The in vitro swelling action of L-thyroxine on rat liver mitochondria as examined photometrically represents an acceleration of a process which the mitochondria are already inherently capable of undergoing spontaneously, as indicated by the identical kinetic characteristics and the extent of thyroxine-induced and spontaneous swelling, the nearly identical pH dependence, and the fact that sucrose has a specific inhibitory action on both types of swelling. However, thyroxine does not appear to be a "catalyst" or coenzyme since it does not decrease the temperature coefficient of spontaneous swelling. The temperature coefficient is very high, approximately 6.0 near 20°. Aging of mitochondria at 0° causes loss of thyroxine sensitivity which correlates closely with the loss of bound DPN from the mitochondria, but not with loss of activity of the respiratory chain or with the efficiency of oxidative phosphorylation. Tests with various respiratory chain inhibitors showed that the oxidation state of bound DPN may be a major determinant of thyroxine sensitivity; the oxidation state of the other respiratory carriers does not appear to influence sensitivity to thyroxine. These facts and other considerations suggest that a bound form of mitochondrial DPN is the "target" of the action of thyroxine. The thyroxine-induced swelling is not reversed by increasing the osmolar concentration of external sucrose, but can be "passively" or osmotically reversed by adding the high-particle weight solute polyvinylpyrrolidone. The mitochondrial membrane becomes more permeable to sucrose during the swelling reaction. On the other hand, thyroxine-induced swelling can be "actively" reversed by ATP in a medium of 0.15 M KCl or NaCl but not in a 0.30 M sucrose medium. The action of ATP is specific; ADP, Mn++, and ethylenediaminetetraacetate are not active. It is concluded that sucrose is an inhibitor of the enzymatic relationship between oxidative phosphorylation and the contractility and

  5. Substrate specific effects of calcium on metabolism of rat heart mitochondria.

    Science.gov (United States)

    Panov, A V; Scaduto, R C

    1996-04-01

    Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased

  6. Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria.

    Science.gov (United States)

    Zhang, Jun; Salminen, Alec; Yang, Xi; Luo, Yong; Wu, Qiangen; White, Matthew; Greenhaw, James; Ren, Lijun; Bryant, Matthew; Salminen, William; Papoian, Thomas; Mattes, William; Shi, Qiang

    2017-08-01

    The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels. Ten endpoints were measured, including oxygen consumption rate, inner membrane potential, cytochrome c release, swelling, reactive oxygen species, and individual respiratory chain complex (I-V) activities. Of the 31 KIs examined only three including sorafenib, regorafenib and pazopanib, all of which are hepatotoxic, caused significant mitochondrial toxicity at concentrations equal to the Cmax, indicating that mitochondrial toxicity likely contributes to the pathogenesis of hepatotoxicity associated with these KIs. At concentrations equal to 100-fold Cmax, 18 KIs were found to be toxic to mitochondria, and among six KIs with BBW-H, mitochondrial injury was induced by regorafenib, lapatinib, idelalisib, and pazopanib, but not ponatinib, or sunitinib. Mitochondrial liability at 100-fold Cmax had a positive predictive power (PPV) of 72% and negative predictive power (NPV) of 33% in predicting human KI hepatotoxicity as defined by product labeling, with the sensitivity and specificity being 62% and 44%, respectively. Similar predictive power was obtained using the criterion of Cmax ≥1.1 µM or daily dose ≥100 mg. Mitochondrial liability at 1-2.5-fold Cmax showed a 100% PPV and specificity, though the NPV and sensitivity were 32% and 14%, respectively. These data provide novel mechanistic insights into KI hepatotoxicity and indicate that

  7. Glucagon effects on the membrane potential and calcium uptake rate of rat liver mitochondria

    International Nuclear Information System (INIS)

    Wingrove, D.E.; Amatruda, J.M.; Gunter, T.E.

    1984-01-01

    It has been widely reported that the in vivo administration of glucagon to rats results in the stimulation of calcium influx in subsequently isolated liver mitochondria. The mechanism of this effect is investigated through simultaneous measurements of calcium uptake rate and mitochondrial membrane potential. This allows the measurement of the calcium uniporter conductance independent of hormonal effects on electron transport or respiration. Two experimental approaches are used. The first involves measuring the uptake of 40-50 nmol of Ca 2+ /mg of mitochondrial protein with the calcium dye antipyrylazo III; the second uses 45 Ca 2+ to follow uptake in the presence of 0.5 to 1.5 μM free calcium, buffered with HEDTA. In both cases a tetraphenyl phosphonium electrode is used to follow membrane potential, and membrane potential is varied using either malonate or butylmalonate in the presence of rotenone. The relative merits of these two approaches are discussed. The conductance of the calcium uniporter is found not to be stimulated by glucagon pretreatment. Also, the relative glucagon stimulation of both calcium influx and membrane potential is found to increase with increasing malonate concentration. These results imply that there is no direct stimulation of calcium uptake into liver mitochondria following glucagon treatment. The results are consistent with a glucagon stimulation of substrate transport, substrate oxidation, or a stimulation of electron transport resulting in an increased membrane potential and secondary stimulation of calcium uptake

  8. [Role of calcium ions in the mechanism of action of acetylcholine on energy metabolism in rat liver mitochondria].

    Science.gov (United States)

    Vatamaniuk, M Z; Artym, V V; Kuka, O B; Doliba, M M; Shostakovs'ka, I V

    1996-01-01

    It is shown that administration of acetylcholine to animals (50 micrograms per 100 g of body weight) leads to the activation of respiration and oxidative phosphorylation in the rat liver mitochondria under oxidation of alpha-ketoglutarate; this effect depends on the concentration of calcium ions in the incubation medium of mitochondria. The rate of ADP-stimulated respiration of mitochondria of experimental animals reaches its maximum level under lower concentrations of Ca2+ than in the control animals. The results of investigation of dependence of acetyl choline effect on respiration of mitochondria on the concentration of alpha-ketoglutarate in calcium and calcium-free incubation medium have shown that the half-maximum effect of acetylcholine is observed in calcium medium at lower concentration of the substrate than in calcium-free medium. The latter indicates to the increase of affinity of alpha-ketoglutarate dehydrogenase to alpha-ketoglutarate under these conditions. It is found out that acetylcholine (1.10(-8) M) increases the rate of ADP- and Ca(2+)-stimulated respiration of mitochondria of isolated perfused rat liver, while mutual effect of verapamyl and niphedipin removes this effect.

  9. Effect of some organic solvents on oxidative phosphorylation in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2013-01-01

    The effect of acetone, acetonitrile, dimethyl sulfoxide (DMSO), ethanol and methanol on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria has been studied. All the organic solvents inhibited the oxidative phosphorylation in a concentration dependent manner, but with differences...... in potencies. Among the tested organic solvents, acetonitrile and acetone were more potent than ethanol, methanol, and DMSO. There was no significant difference in oxidative phosphorylation, compared to controls, when the concentrations of acetone was below 1% (v/v), of acetonitrile below 2% (v/v), of DMSO...... below 10% (v/v), of ethanol below 5% or of methanol below 2%, respectively. There was complete inhibition of oxidative phosphorylation at 50% (v/v) of acetone, acetonitrile and ethanol. But in the case of DMSO and methanol there were some residual activities observed at the 50% concentration level. DMSO...

  10. Novel function of glutathione transferase in rat liver mitochondrial membrane: Role for cytochrome c release from mitochondria

    International Nuclear Information System (INIS)

    Lee, Kang Kwang; Shimoji, Manami; Hossain, Quazi Sohel; Sunakawa, Hajime; Aniya, Yoko

    2008-01-01

    Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST1. In the present study, we aimed to determine whether mtMGST1 also undergoes activation and about its function. When rats were treated with galactosamine/lipopolysaccharide (GalN/LPS), mtMGST1 activity was significantly increased, and the increased activity was reduced by the disulfide reducing agent dithiothreitol. In mitochondria from GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed protein glutathione disulfides (glutathionylation) were detected. In addition, cytochrome c release from mitochondria isolated from GalN/LPS-treated rats was observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of mitochondria from control rats with diamide and diamide plus GSH in vitro resulted in dimer- and mixed disulfide bond-mediated activation of mtMGST1, respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c release from the mitochondria, and the release was prevented by treatment with anti-MGST1 antibodies. In addition, diamide plus GSH treatment caused mitochondrial swelling accompanied by cytochrome c release, which was inhibited by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also inhibited by CsA and BKA. These results indicate that mtMGST1 is activated through mixed disulfide bond formation that contributes to cytochrome c release from mitochondria through the MPT pore

  11. 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

  12. Effects of Aluminium on Rat Brain Mitochondria Bioenergetics: an In vitro and In vivo Study.

    Science.gov (United States)

    Iglesias-González, Javier; Sánchez-Iglesias, Sofía; Beiras-Iglesias, Andrés; Méndez-Álvarez, Estefanía; Soto-Otero, Ramón

    2017-01-01

    Numerous studies have highlighted the potential of aluminium as an aetiological factor for some neurodegenerative disorders, particularly Alzheimer's disease and Parkinson's disease. Our previous studies have shown that aluminium can cause oxidative stress, reduce the activity of some antioxidant enzymes, and enhance the dopaminergic neurodegeneration induced by 6-hydroxydopamine in an experimental model of Parkinson's disease in rats. We now report a study on the effects caused by aluminium on mitochondrial bioenergetics following aluminium addition and after its chronic administration to rats. To develop our study, we used a high-resolution respirometry to test the mitochondrial respiratory capacities under the conditions of coupling, uncoupling, and non-coupling. Our study showed alterations in leakiness, a reduction in the maximum capacity of complex II-linked respiratory pathway, a decline in the respiration efficiency, and a decrease in the activities of complexes III and V in both models studied. The observed effects also included both an alteration in mitochondrial transmembrane potential and a decrease in oxidative phosphorylation capacity when relatively high concentrations of aluminium were added to the isolated mitochondria. These findings contribute to explain both the ability of aluminium to generate oxidative stress and its suggested potential to act as an etiological factor by promoting the progression of neurodegenerative disorders such as Parkinson's disease.

  13. Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats.

    Science.gov (United States)

    Tu, Huiyin; Liu, Jinxu; Zhu, Zhen; Zhang, Libin; Pipinos, Iraklis I; Li, Yu-Long

    2012-01-01

    Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage-gated sodium (Na(v)) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in the CHF state. The present study examined the role of mitochondria-derived superoxide in the reduced Na(v) channel function in coronary artery ligation-induced CHF rats. CHF decreased the protein expression and activity of mitochondrial complex enzymes and manganese SOD (MnSOD) and elevated the mitochondria-derived superoxide level in the nodose neurons compared with those in sham nodose neurons. Adenoviral MnSOD (Ad.MnSOD) gene transfection (50 multiplicity of infection) into the nodose neurons normalized the MnSOD expression and reduced the elevation of mitochondrial superoxide in the nodose neurons from CHF rats. Ad.MnSOD also partially reversed the reduced protein expression and current density of the Na(v) channels and the suppressed cell excitability (the number of action potential and the current threshold for inducing action potential) in aortic baroreceptor neurons from CHF rats. Data from the present study indicate that mitochondrial dysfunction, including decreased protein expression and activity of mitochondrial complex enzymes and MnSOD and elevated mitochondria-derived superoxide, contributes to the reduced Na(v) channel activation and cell excitability in the aortic baroreceptor neurons in CHF rats.

  14. Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

    International Nuclear Information System (INIS)

    Konopka, K.; Romslo, I.; Bergen Univ.

    1981-01-01

    1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

  15. 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...

  16. Volume effect on the radiation injury of rat kidney

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  17. Histopathological effects of doxorubicin on kidneys in rats

    Directory of Open Access Journals (Sweden)

    I.A. Ali

    2014-06-01

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

  18. Toxicity of thallium on isolated rat liver mitochondria: the role of oxidative stress and MPT pore opening.

    Science.gov (United States)

    Eskandari, M R; Mashayekhi, Vida; Aslani, Majid; Hosseini, Mir-Jamal

    2015-02-01

    Thallium(I) is a highly toxic heavy metal; however, up to now, its mechanisms are poorly understood. The authors' previous studies showed that this compound could induce reactive oxygen species (ROS) formation, reduced glutathione (GSH) oxidation, membrane lipid peroxidation, and mitochondrial membrane potential (MMP) collapse in isolated rat hepatocyte. Because the liver is the storage site of thallium, it seems that the liver mitochondria are one of the important targets for hepatotoxicity. In this investigation, the effects of thallium on mitochondria were studied to investigate its mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with different concentrations of thallium (25-200 µM). Thallium(I)-treated mitochondria showed a marked elevation in oxidative stress parameters accompanied by MMP collapse when compared with the control group. These results showed that different concentrations of thallium (25-200 µM) induced a significant (P thallium(I)-induced liver toxicity is a result of the disruptive effect of this metal on the mitochondrial respiratory complexes (I, II, and IV), which are the obvious causes of metal-induced ROS formation and ATP depletion. The latter two events, in turn, trigger cell death signaling via opening of mitochondrial permeability transition pore and cytochrome c expulsion. © 2013 Wiley Periodicals, Inc.

  19. Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency

    Directory of Open Access Journals (Sweden)

    G. P. Kopylchuk

    2016-04-01

    Full Text Available The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide generation, the level of oxidative modification of mitochondrial proteins in the liver of rats with toxic hepatitis was investigated on the background of alimentary protein deficiency. We did not find significant increases of the intensity of free radical processes in liver mitochondria of rats maintained on the protein-deficient ration. The most significant intensification of free radical processes in liver mitochondria is observed under the conditions of toxic hepatitis, induced on the background of alimentary protein deprivation. Under these conditions the aggravation of all studied forms of reactive oxygen species generation was observed in liver mitochondria. The generation rates were increased as follows: O2 – by 1.7 times, Н2О2 – by 1.5 times, •ОН – practically double on the background of accumulation of oxidized mitochondria-derived proteins. The established changes in thiol groups’ redox status of respiratory chain proteins insoluble in 0.05 M sodium-phosphate buffer (pH 11.5, and changes of their carbonyl derivatives content may be considered as one of the regulatory factors of mitochondrial energy-generating function.

  20. Effect of temperature on fatty acid metabolism in skeletal muscle mitochondria of untrained and endurance-trained rats.

    Science.gov (United States)

    Zoladz, Jerzy A; Koziel, Agnieszka; Broniarek, Izabela; Woyda-Ploszczyca, Andrzej M; Ogrodna, Karolina; Majerczak, Joanna; Celichowski, Jan; Szkutnik, Zbigniew; Jarmuszkiewicz, Wieslawa

    2017-01-01

    We studied the effects of various assay temperatures, representing hypothermia (25°C), normothermia (35°C), and hyperthermia (42°C), on the oxidation of lipid-derived fuels in rat skeletal muscle mitochondria of untrained and endurance-trained rats. Adult 4-month-old male Wistar rats were assigned to a training group (rats trained on a treadmill for 8 weeks) or a sedentary control group. In skeletal muscle mitochondria of both control and trained rats, an increase in the assay temperature from 25°C to 42°C was accompanied by a consistent increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate. Moreover, endurance training increased mitochondrial capacity to oxidize the lipid-derived fuels at all studied temperatures. The endurance training-induced increase in mitochondrial capacity to oxidize fatty acids was accompanied by an enhancement of mitochondrial biogenesis, as shown by the elevated expression levels of Nrf2, PGC1α, and mitochondrial marker and by the elevated expression levels of mitochondrial proteins involved in fatty acid metabolism, such as fatty acid transporter CD36, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase (ACADS). We conclude that hyperthermia enhances but hypothermia attenuates the rate of the oxidation of fatty acids and glycerol-3-phosphate in rat skeletal muscle mitochondria isolated from both untrained and trained rats. Moreover, our results indicate that endurance training up-regulates mitochondrial biogenesis markers, lipid-sustained oxidative capacity, and CD36 and CPT1A proteins involved in fatty acid transport, possibly via PGC1α and Nrf2 signaling pathways.

  1. Effect of temperature on fatty acid metabolism in skeletal muscle mitochondria of untrained and endurance-trained rats.

    Directory of Open Access Journals (Sweden)

    Jerzy A Zoladz

    Full Text Available We studied the effects of various assay temperatures, representing hypothermia (25°C, normothermia (35°C, and hyperthermia (42°C, on the oxidation of lipid-derived fuels in rat skeletal muscle mitochondria of untrained and endurance-trained rats. Adult 4-month-old male Wistar rats were assigned to a training group (rats trained on a treadmill for 8 weeks or a sedentary control group. In skeletal muscle mitochondria of both control and trained rats, an increase in the assay temperature from 25°C to 42°C was accompanied by a consistent increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate. Moreover, endurance training increased mitochondrial capacity to oxidize the lipid-derived fuels at all studied temperatures. The endurance training-induced increase in mitochondrial capacity to oxidize fatty acids was accompanied by an enhancement of mitochondrial biogenesis, as shown by the elevated expression levels of Nrf2, PGC1α, and mitochondrial marker and by the elevated expression levels of mitochondrial proteins involved in fatty acid metabolism, such as fatty acid transporter CD36, carnitine palmitoyltransferase 1A (CPT1A, and acyl-CoA dehydrogenase (ACADS. We conclude that hyperthermia enhances but hypothermia attenuates the rate of the oxidation of fatty acids and glycerol-3-phosphate in rat skeletal muscle mitochondria isolated from both untrained and trained rats. Moreover, our results indicate that endurance training up-regulates mitochondrial biogenesis markers, lipid-sustained oxidative capacity, and CD36 and CPT1A proteins involved in fatty acid transport, possibly via PGC1α and Nrf2 signaling pathways.

  2. Protective effects of potassium transport in mitochondria from rat myometrium under activation of mitochondrial permeability transition pore

    Directory of Open Access Journals (Sweden)

    O. B. Vadzyuk

    2015-12-01

    Full Text Available We demonstrated using PBFI K+-sensitive fluorescent probe an enhancement of both components of K+-cycle – the ATP-sensitive K+-uptake and quinine-sensitive K+/H+-exchange – under the Ca2+ induced opening­ of mitochondrial permeability transition pore (MPTP in rat myometrium mitochondria. Addition of CaCl2 (100 μM to K+-free medium results in the enhancement of reactive oxygen species (ROS production, which was eliminated by cyclosporine A. Addition of CaCl2 to K+-rich medium did not increase the rate of ROS production, but blocking of mitoK+ATP-channels with glybenclamide (10 μM increased production of ROS. We conclude that K+-cycle exerts a protective influence in mitochondria from rat myometrium by regulation of matrix volume and rate of ROS production under the condition of Ca2+-induced MPTP.

  3. Hydrocortisone and insulin effect on oxidative phosphorylation in mitochondria of liver and spleen th rats exposed to fast neutrons

    International Nuclear Information System (INIS)

    Sutkovoj, D.A.; Alferov, A.N.; Letov, V.N.

    1979-01-01

    Total-body exposure of rats to fast neutrons (100 rad) elicits an increase in the content of 11-oxycorticosteroids in blood plasma and an appreciable decrease in the respiratory and phosphorylation activity of liver and spleen mitochondria. Administration of hydrocortisone (50 mg/kg) and particularly insulin (2 units/kg) intensifies energy generation in the liver. In the spleen, a beneficial effect was only produced by insulin. Glucocorticoid considerably aggravates the postradiation impairment of oxidative phosphorylation

  4. Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

    Directory of Open Access Journals (Sweden)

    Norshalizah Mamikutty

    2015-01-01

    Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

  5. Novel distribution of calreticulin to cardiomyocyte mitochondria and its increase in a rat model of dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ming [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Wei, Jin, E-mail: weijindr@163.com [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Li, Yali [Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Shan, Hu; Yan, Rui; Lin, Lin [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Zhang, Qiuhong [Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China); Xue, Jiahong [Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi (China)

    2014-06-20

    Highlights: • Calreticulin can also be found in cardiomyocyte mitochondria. • The mitochondrial content of calreticulin is increased in DCM hearts. • Increased expression of mitochondrial CRT may induce mitochondrial damage. • Mitochondrial CRT may inhibit the phosphorylation of mitochondrial STAT3. - Abstract: Background: Calreticulin (CRT), a Ca{sup 2+}-binding chaperone of the endoplasmic reticulum, can also be found in several other locations including the cytosol, nucleus, secretory granules, the outer side of the plasma membrane, and the extracellular matrix. Whether CRT is localized at mitochondria of cardiomyocytes and whether such localization is affected under DCM are still unclear. Methods and results: The DCM model was generated in rats by the daily oral administration of furazolidone for thirty weeks. Echocardiographic and hemodynamic studies demonstrated enlarged left ventricular dimensions and reduced systolic and diastolic function in DCM rats. Immuno-electron microscopy and Western blot showed that CRT was present in cardiomyocyte mitochondria and the mitochondrial content of CRT was increased in DCM hearts (P < 0.05). Morphometric analysis showed notable myocardial apoptosis and mitochondrial swelling with fractured or dissolved cristae in the DCM hearts. Compared with the control group, the mitochondrial membrane potential level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P < 0.05), and the myocardial apoptosis index and the caspase activities of caspase-9 and caspase-3 were significantly increased (P < 0.05). Pearson linear correlation analysis showed that the mitochondrial content of CRT had negative correlations with the mitochondrial function, and a positive correlation with myocardial apoptosis index (P < 0.001). The protein expression level of cytochrome c and the phosphorylation activity of STAT3 in the

  6. A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

    Science.gov (United States)

    Kajma, Anna; Szewczyk, Adam

    2012-10-01

    Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Divalent phosphate is a counterion for carboxyatractyloside-insensitive adenine nucleotide transport in rat liver mitochondria

    International Nuclear Information System (INIS)

    Nosek, M.T.; Aprille, J.R.

    1986-01-01

    Unidirectional, carboxyatractyloside(CAT)-insensitive adenine nucleotide (AdN) fluxes have been studied in isolated rat liver mitochondria (mito). Previous work has shown that ATP x Mg transport in one direction is coupled to ATP x Mg or P/sub i/ transport in the opposite direction. The purpose of this study was to determine whether divalent HPO 4 2- or monovalent H 2 PO 4 - is the transported phosphate species. The authors used the monofluorophosphate (PO 3 F 2- ) and difluorophosphate (PO 2 F 2 - ) analogues as potential counterions forAdN efflux. After a preincubation on ice with 14 C-ADP to label the matrix AdN, efflux was measured at 30 0 C, pH 7.4, in 225mM sucrose, 10mM KCl, 5mM MgCl 2 , 5mM glutamate, 5mM malate, 10mM Tris, 0.5mM P/sub i/, 1mM ATP, and 5μM CAT. With no other additions efflux was -0.62 +/- 0.20 nmole/minute/mg protein. The data supports the hypothesis that divalent but not monovalent phosphate can act as a counterion for ATPx Mg transport over this CAT-insensitive carrier

  8. Stoichiometry of H+ ejection during respiration-dependent accumulation of Ca2+ by rat liver mitochondria.

    Science.gov (United States)

    Brand, M D; Chen, C H; Lehninger, A L

    1976-02-25

    We have investigated the energy-dependent uptake of Ca2+ by rat liver mitochondria with succinate as respiratory substrate with rotenone added to block NAD-linked electron transport. In the presence of 3-hydroxybutyric or other permeant monocarboxylic acids Ca2+ was taken up to extents approaching those seen in the presence of phosphate. The quantitative relationship between cation and anion uptake was determined from the slope of a plot of 3-hydroxybutyrate uptake against Ca2+ uptake, a method which allowed determination of the stoichiometry without requiring ambiguous corrections for early nonenergized or nonstoichiometric binding events. This procedure showed that 2 molecules of 3-hydroxtbutyrate were accumulated with each Ca2+ ion. Under these conditions close to 2 Ca2+ ions and 4 molecules of 3-hydroxybutyrate were accumulated per pair of electrons per energy-conserving site of the respiratory chain. Since 3-hydroxybutyrate must be protonated to pass the membrane as the undissociated free acid, it is concluded that 4 protons were ejected (and subsequently reabsorbed) per pair of electrons per energy-conserving site, in contrast to the value 2.0 postulated by the chemiosmotic hypothesis.

  9. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ye Ding

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

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

    Science.gov (United States)

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

    2011-01-01

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

  13. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water

    Science.gov (United States)

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury. PMID:26316710

  14. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

    Science.gov (United States)

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

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

    Science.gov (United States)

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

    2016-06-01

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

  16. The effect of alpha-tocopheryl succinate on succinate respiration in rat liver mitochondria

    Czech Academy of Sciences Publication Activity Database

    Sobotka, O.; Drahota, Zdeněk; Kučera, O.; Endlicher, R.; Rauchová, Hana; Červinková, Z.

    2015-01-01

    Roč. 64, Suppl.5 (2015), S609-S615 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : tocopheryl succinate * Complex II * liver * mitochondria * homogenate * hepatocytes Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  17. Identification of the protein responsible for pyruvate transport into rat liver and heart mitochondria by specific labelling with [3H]N-phenylmaleimide.

    OpenAIRE

    Thomas, A P; Halestrap, A P

    1981-01-01

    1. N-Phenylmaleimide irreversibly inhibits pyruvate transport into rat heart and liver mitochondria to a much greater extent than does N-ethylmaleimide, iodoacetate or bromopyruvate. alpha-Cyanocinnamate protects the pyruvate transporter from attack by this thiol-blocking reagent. 2. In both heart and liver mitochondria alpha-cyanocinnamate diminishes labelling by [3H]N-phenylmaleimide of a membrane protein of subunit mol.wt. 15000 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis...

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

    Directory of Open Access Journals (Sweden)

    Indira Pokkunuri

    2016-01-01

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

  19. The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

    Science.gov (United States)

    Tian, Shan; Zhu, Fengping; Hu, Ruiping; Tian, Song; Chen, Xingxing; Lou, Dan; Cao, Bing; Chen, Qiulei; Li, Bai; Li, Fang; Bai, Yulong; Wu, Yi; Zhu, Yulian

    2018-01-01

    Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Studies on the lipid peroxidation in mitochondria of x-ray whole-body irradiated rat liver, 2

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroshi

    1976-01-01

    The results of investigation made on the mitochondria of rat liver on the 3rd day after irradiation of 650 R are as follows: After lipid peroxidation, the mitochondria showed a decrease of polyenoic acids (C-20:4, C-22:6) suggesting that polyenoic acids are the substrate of the reaction. Unsaturated fatty acids were decreased due to the decrement of C-18:1 and C-18:2, and polyenoic acid was relatively increased. These changes were transient, reaching a maximum on the 3rd day after irradiation. The rate of peroxidation in total lipids extracted form normal mitochondria was the same as that from whole-body irradiated mitochondria. There was no lag in the induction period in either reaction. Marked peroxidation of the total lipid was seen in the phospholipid fraction and slight peroxidation in the simple lipid fractions. No significant effect of whole-body irradiation on the peroxidation activities of the phospholipid was observed. With thin-layer chromatography, peroxidation of subfractionated phospholipid showed marked activity in the lecithin and aminophosphatide fractions containing large amounts of C-20:4 and C-22.6. Recovery of activity in the subfractions was greater than that in the total phospholipid. The effect of whole-body irradiation appeared to be significant in these subfractions. However no relationships could be seen between the activities peroxidation and the fatty acid composition of the subfractions. The ratio of phospholipid to total lipid increased in whole-body irradiated samples. From these findings there was a discussion of whether or not Fe ++ -induced lipid peroxidation at the mitochondrial level is due to change in the composition of fatty acid and the association of lipid in the membrane. (Evans, J.)

  1. Theoretical paper: exploring overlooked natural mitochondria-rejuvenative intervention: the puzzle of bowhead whales and naked mole rats.

    Science.gov (United States)

    Prokopov, Arkadi F

    2007-12-01

    There is an imperative need for exploring and implementing mitochondria-rejuvenative interventions that can bridge the current gap toward the step-by step realization of strategies for engineered negligible senescence (SENS) agenda. Recently discovered in mammals, natural mechanism mitoptosis-a selective "suicide" of mutated mitochondria-can facilitate continuous purification of mitochondrial pool in an organism from the most reactive oxygen species (ROS)-producing mitochondria. Mitoptosis, which is considered to be the first stage of ROS-induced apoptosis, underlies follicular atresia (a "quality control" mechanism in female germline cells that eliminates most germinal follicles in female embryos). Mitoptosis can be also activated in adult postmitotic somatic cells by evolutionary conserved phenotypic adaptations to intermittent oxygen restriction (IOR) and synergistically acting intermittent caloric restriction (ICR). IOR and ICR are common in mammals and seem to underlie extraordinary longevity and augmented cancer resistance in bowhead whales (Balena mysticetus) and naked mole rats (Heterocephalus glaber). Furthermore, in mammals IOR can facilitate continuous stromal stem cells-de-pendent tissue repair. A comparative analysis of IOR and ICR mechanisms in both mammals, in conjunction with the experience of decades of biomedical and clinical research on emerging preventative, therapeutic, and rehabilitative modality-the intermittent hypoxic training/therapy (IHT)-indicates that the notable clinical efficiency of IHT is based on the universal adaptational mechanisms that are common in mammals. Further exploration of natural mitochondria-preserving and -rejuvenating strategies can help refinement of IOR- and ICR-based synergistic protocols, having value in clinical human rejuvenation.

  2. 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

  3. 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

  4. Differentiating between apparent and actual rates of H2O2 metabolism by isolated rat muscle mitochondria to test a simple model of mitochondria as regulators of H2O2 concentration

    Science.gov (United States)

    Treberg, Jason R.; Munro, Daniel; Banh, Sheena; Zacharias, Pamela; Sotiri, Emianka

    2015-01-01

    Mitochondria are often regarded as a major source of reactive oxygen species (ROS) in animal cells, with H2O2 being the predominant ROS released from mitochondria; however, it has been recently demonstrated that energized brain mitochondria may act as stabilizers of H2O2 concentration (Starkov et al. [1]) based on the balance between production and the consumption of H2O2, the later of which is a function of [H2O2] and follows first order kinetics. Here we test the hypothesis that isolated skeletal muscle mitochondria, from the rat, are able to modulate [H2O2] based upon the interaction between the production of ROS, as superoxide/H2O2, and the H2O2 decomposition capacity. The compartmentalization of detection systems for H2O2 and the intramitochondrial metabolism of H2O2 leads to spacial separation between these two components of the assay system. This results in an underestimation of rates when relying solely on extramitochondrial H2O2 detection. We find that differentiating between these apparent rates found when using extramitochondrial H2O2 detection and the actual rates of metabolism is important to determining the rate constant for H2O2 consumption by mitochondria in kinetic experiments. Using the high rate of ROS production by mitochondria respiring on succinate, we demonstrate that net H2O2 metabolism by mitochondria can approach a stable steady-state of extramitochondrial [H2O2]. Importantly, the rate constant determined by extrapolation of kinetic experiments is similar to the rate constant determined as the [H2O2] approaches a steady state. PMID:26001520

  5. Inhibition of lipid peroxidation induced by γ- radiation and AAPH in rat liver and brain mitochondria by mushrooms

    International Nuclear Information System (INIS)

    Lakshmi, B.; Janardhanan, K.K.; Tilak, J.C.; Devasagayam, T.P.A.; Adhikari, S.

    2005-01-01

    Exposure to radiation or 2.2' Azobis(2-amidopropane) dihydrochloride (AAPH) induces generation of reactive oxygen species (ROS) especially hydroxyl radical ( . OH) and peroxyl radical (ROO . ), which are capable of inducing lipid peroxidation. Our earlier studies have demonstrated that extracts of the medicinal and edible mushrooms Ganoderma lucidum, Pleurotus florida, Pleurotus sajor-caju and Phellinus rimosus possessed significant antioxidant activity, measured as radical scavenging. In the present study, we examined the protective effect of these mushroom extracts against radiation- and AAPH-induced lipid peroxidation using rat liver and brain mitochondria as model systems. The results obtained showed that the investigated mushroom extracts significantly inhibited the formation of lipid hydroperoxide and thiobarbituric acid reactive substances, indicating membrane protective effects. The finding suggests the profound protective effect of the extracts of the fruiting bodies of G. lucidum, P. florida, P. sajor-caju and P. rimosus against lipid peroxidation by two major forms of ROS capable of inducing this type of damage in a major organelle, the mitochondria from both rat liver and brain. This observation can possibly explain the health benefits of these mushrooms. (author)

  6. Mitochondrial toxicity of selective COX-2 inhibitors via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    Cyclooxygenase-2 (COX-2) inhibitors (coxibs) are non-steroidal anti-inflammatory drugs (NSAIDs) designed to selectively inhibit COX-2. However, drugs of this therapeutic class are associated with drug induced liver injury (DILI) and mitochondrial injury is likely to play a role. The effects...... of selective COX-2 inhibitors on inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria were investigated. The order of potency of inhibition of ATP synthesis was: lumiracoxib (IC50: 6.48 ± 2.74 μM)>celecoxib (IC50: 14.92 ± 6.40 μM)>valdecoxib (IC50: 161.4 ± 28.6 μM)>rofecoxib (IC50...... correlation (with r(2)=0.921) was observed between the potency of inhibition of ATP synthesis and the log P values. The in vitro metabolism of coxibs in rat liver mitochondria yielded for each drug substance a major single metabolite and identified a hydroxy metabolite with each of the coxibs...

  7. [Features of noradrenaline stimulation of rat liver mitochondria respiration by ADP and calcium ions].

    Science.gov (United States)

    Stefankiv, Iu S; Babskyĭ, A M; Shostakovska, Y V

    1995-01-01

    A single administration of a physiological dose of noradrenaline to animals. in contrast to adrenaline, stimulates the respiration of mitochondria not only under oxidation of FAD-dependent Krebbs cycle substrate of the succinase but also HAD-dependent substrate of alpha-ketoglutarate. In the both cases the phosphorylation rate increases, since the action of noradrenaline, separating the respiration and oxidative phosphorylation, was not found. Noradrenaline increases the capacity of mitochondria to more actively absorb calcium ions under oxidation of succinate than under that of alpha-ketoglutarate.

  8. 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 ...

  9. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-09-01

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

  11. Autoradiographic localization of benzodiazepine receptors in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-11-01

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

  12. 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.

  13. Biosynthesis of agmatine in isolated mitochondria and perfused rat liver: studies with 15N-labelled arginine

    Science.gov (United States)

    2005-01-01

    An important but unresolved question is whether mammalian mitochondria metabolize arginine to agmatine by the ADC (arginine decarboxylase) reaction. 15N-labelled arginine was used as a precursor to address this question and to determine the flux through the ADC reaction in isolated mitochondria obtained from rat liver. In addition, liver perfusion system was used to examine a possible action of insulin, glucagon or cAMP on a flux through the ADC reaction. In mitochondria and liver perfusion, 15N-labelled agmatine was generated from external 15N-labelled arginine. The production of 15N-labelled agmatine was time- and dose-dependent. The time-course of [U-15N4]agmatine formation from 2 mM [U-15N4]arginine was best fitted to a one-phase exponential curve with a production rate of approx. 29 pmol·min−1·(mg of protein)−1. Experiments with an increasing concentration (0– 40 mM) of [guanidino-15N2]arginine showed a Michaelis constant Km for arginine of 46 mM and a Vmax of 3.7 nmol·min−1·(mg of protein)−1 for flux through the ADC reaction. Experiments with broken mitochondria showed little changes in Vmax or Km values, suggesting that mitochondrial arginine uptake had little effect on the observed Vmax or Km values. Experiments with liver perfusion demonstrated that over 95% of the effluent agmatine was derived from perfusate [guanidino-15N2]arginine regardless of the experimental condition. However, the output of 15N-labelled agmatine (nmol·min−1·g−1) increased by approx. 2-fold (P<0.05) in perfusions with cAMP. The findings of the present study provide compelling evidence that mitochondrial ADC is present in the rat liver, and suggest that cAMP may stimulate flux through this pathway. PMID:15656789

  14. Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.

    Science.gov (United States)

    Sil, Rajarshi; Chakraborti, Abhay Sankar

    2016-09-01

    Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Sotiria Palimeri

    2016-06-01

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

  19. 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....

  20. Persistent changes in the initial rate of pyruvate transport by isolated rat liver mitochondria after preincubation with adenine nucleotides and calcium ions

    NARCIS (Netherlands)

    Vaartjes, W.J.; Breejen, J.N. den; Geelen, M.J.H.; Bergh, S.G. van den

    1980-01-01

    1. Preincubation of isolated rat-liver mitochondria in the presence of adenine nucleotides or Ca2+ results in definite and persistent changes in the initial rate of pyruvate transport. 2. These changes in the rate of pyruvate transport are accompanied by equally persistent changes in the opposite

  1. Analysis of effects of 2,2',5,5'-tetracholorobiphenyl on the flux control in oxidative phosphorylation system in rat liver mitochondria.

    NARCIS (Netherlands)

    Mildaziene, V.; Nauciene, Z.; Baniene, R.; Demin, O.V.; Krab, K.

    2002-01-01

    Modular kinetic analysis reveals that the environmental pollutant 2,2′,5,5′tetrachlorobiphenyl (2,2′,5,5′-TCB) affects a large number of steps in oxidative phosphorylation in rat liver mitochondria. 2,2′,5,5′-TCB increases membrane permeability to ions, and inhibits NADH dehydrogenase, cytochrome

  2. 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...

  3. Glycerophosphate-dependent peroxide production by brown fat mitochondria from newborn rats

    Czech Academy of Sciences Publication Activity Database

    Drahota, Zdeněk; Rauchová, Hana; Ješina, Pavel; Vojtíšková, Alena; Houštěk, Josef

    2003-01-01

    Roč. 22, - (2003), s. 93-102 ISSN 0231-5882 R&D Projects: GA MŠk LN00A079; GA ČR GA303/03/0799; GA MŠk OC 918.50; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 111100003 Keywords : Brown adipose tissue mitochondria * glycerophosphate dehydrogenase * hydrogen peroxide Subject RIV: CE - Biochemistry Impact factor: 0.794, year: 2003

  4. Inhibition of Palmityl Carnitine Oxidation in Rat Liver Mitochondria by Tert-Butyl Hydroperoxide

    Czech Academy of Sciences Publication Activity Database

    Červinková, Z.; Rauchová, Hana; Křiváková, P.; Drahota, Zdeněk

    2008-01-01

    Roč. 57, č. 1 (2008), s. 133-136 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GD303/03/H065; GA ČR(CZ) GA305/04/0500; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50110509 Keywords : liver mitochondria * palmityl carnitine oxidation * tert-butylhydroperoxide Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

  5. 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 ...

  6. 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

  7. Direct Effects of (−-Epicatechin and Procyanidin B2 on the Respiration of Rat Heart Mitochondria

    Directory of Open Access Journals (Sweden)

    Dalia M. Kopustinskiene

    2015-01-01

    Full Text Available Flavonol (−-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (−-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (−-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control on substrate-driven (State 2 mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (−-Epicatechin at higher concentrations (from 0.27 µg/mL significantly decreased (up to 15% substrate- and ADP-driven (State 3 mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7–17.9 ng/mL inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (−-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (−-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.

  8. Direct measurement of the initial proton extrusion to oxygen uptake ratio accompanying succinate oxidation by rat liver mitochondria.

    Science.gov (United States)

    Setty, O H; Shrager, R I; Bunow, B; Reynafarje, B; Lehninger, A L; Hendler, R W

    1986-01-01

    The problem of obtaining very early ratios for the H+/O stoichiometry accompanying succinate oxidation by rat liver mitochondria was attacked using new techniques for direct measurement rather than extrapolations based on data obtained after mixing and the recovery of the electrode from initial injection of O2. Respiration was quickly initiated in a thoroughly mixed O2-containing suspension of mitochondria under a CO atmosphere by photolysis of the CO-cytochrome c oxidase complex-. Fast responding O2 and pH electrodes were used to collect data every 10 ms. The response time for each electrode was experimentally measured in each experiment and suitable corrections for electrode relaxations were made. With uncorrected data obtained after 0.8 s, the extrapolation back to zero time on the basis of single-exponential curve fitting confirmed values close to 8.0 as previously reported (Costa et al., 1984). The data directly obtained, however, indicate an initial burst in H+/O ratio that peaked to values of approximately 20 to 30 prior to 50 ms and which was no longer evident after 0.3 s. Newer information and considerations that place all extrapolation methods in question are discussed. PMID:3019443

  9. 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

  10. 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

  11. Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats.

    Science.gov (United States)

    Ajith, Thekkuttuparambil Ananthanarayanan; Nima, Nalin; Veena, Ravindran Kalathil; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

    2014-01-01

    According to the mitochondrial mutation theory of aging, the impairment of mitochondrial functions and decline of cellular bioenergetics are induced by highly reactive oxygen species (ROS). Supplementation with antioxidants may protect mitochondria against respiration-linked oxidative stress and reduce decay by preserving genomic and structural integrity. Several clinical studies have reported beneficial effects of α-lipoic acid (LA) administration in individuals with Alzheimer's disease, particularly improving their spatial orientation; however, no studies have been reported on the effects of palladium α-lipoic acid (Pd-LA). The current study examined the effects of the Pd-LA complex on mitochondrial energy status in the brains of aged rats. The study used male Wistar rats, some that were older than 24 mo and weighed approximately 350 ± 50 g and some that were younger than 24 mo and weighed approximately 175 ± 25 g. The research team divided the rats into 5 groups of 6 rats. The study was conducted at the Amala Cancer Research Centre in Amala Nagar, Thrissur, Kerala, India. Three groups of rats were controls: (1) young controls administered no solution, (2) aged controls administered 1 mL/kg of a 0.25% solution (PO) of sodium hydroxide (NaOH), and (3) positive aged controls treated with LA (7.6 mg/kg, PO) dissolved in an alkaline saline (0.25% NaOH, w/v). Two groups were intervention groups: (1) aged rats treated with 1.2 mg/kg of Pd-LA (PO) and (2) aged rats treated with 23.5 mg/kg of Pd-LA (PO). The research team administered the solutions once daily for 30 d. After 30 d, all animals were sacrificed. The research team evaluated serum transaminases, lactate dehydrogenase (LDH), serum urea, and creatinine. The activities of superoxide dismutase (SOD), catalase (CAT), and the levels of reduced glutathione (GSH) were determined in the blood samples. Krebs cycle dehydrogenases were evaluated in the brain mitochondria. Furthermore, the activities of the

  12. Oxidative metabolism of 5-o-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria.

    Science.gov (United States)

    dos Santos, Michel D; Martins, Patrícia R; dos Santos, Pierre A; Bortocan, Renato; Iamamoto, Y; Lopes, Norberto P

    2005-09-01

    Synthetic metalloporphyrins, in the presence of monooxygen donors, are known to mimic the various reactions of cytochrome P450 enzymes systems in the oxidation and oxygenation of various drugs and biologically active compounds. This paper reports an HPLC-MS-MS investigation of chlorogenic acid (CGA) oxidation by iodosylbenzene using iron(III) tetraphenylporphyrin chloride as catalyst. The oxidation products have been detected by sequential MS analyses. In addition, CGA was submitted to an in vitro metabolism assay employing isolated rat liver mitochondria. The single oxidized product obtained from mitochondrial metabolism corresponds to the major product formed by the metalloporphyrin-catalyzed reaction. These results indicate that biomimetic oxidation reactions, in addition to in vitro metabolism assays employing isolated organs/organelles, could replace some in vivo metabolism studies, thus minimizing the problems related to the use of a large number of living animals in experimental research.

  13. The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

    Science.gov (United States)

    Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

    2010-06-01

    The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

  14. Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inh......Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation...... of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism...

  15. Purification and characterization of the reconstitutively active P/sub i//H/sup +/ symporter from rat liver mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, R.S.; Pratt, R.D.; Pedersen, P.L.

    1986-05-01

    A highly purified preparation of reconstitutively active P/sub i//H/sup +/ symporter has been obtained from rat liver mitochondria. The carrier is isolated by extraction of hypotonically shocked mitoplasts with Triton X-114 in the presence of cardiolipin followed by sequential chromatography on hydroxylapatite, DEAE-Sepharose CL-6B, and Affi-Gel 501. Upon incorporation of the final Affi-Gel eluate into phospholipid vesicles, an N-ethylmaleimide (NEM)-sensitive P/sub i//P/sub i/ exchange of greater than 15 ..mu..mol/min/mg protein has been measured. This exchange is characterized by a first order rate constant of 0.85 min/sup -1/ and a t/sub 1/2/ of 49 sec. Furthermore, /sup 32/P/sub i/ uptake into vesicles can be inhibited by SH reagents and by the lysine reactive reagent dansyl chloride. Coomassie-stained SDS polyacrylamide gradient gels verify the high purity of this fraction and indicate the presence of two bands, of nearly equivalent staining intensity, at 33 kDa and 35 kDa. A small amount of higher molecular weight material also appears at approx. 61 kDa. Alkylation of the purified fraction with NEM causes the two lower molecular weight protein bands to migrate as a single species at 35 kDa which binds (/sup 3/H)NEM. It is concluded that the purifed protein represents a nearly homogeneous form of the NEM-sensitive P/sub i//H/sup +/ symporter of rat liver mitochondria. Additionally, the purified carrier appears to contain cysteine and lysine residues that are essential for activity.

  16. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

    Science.gov (United States)

    Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

    2017-03-15

    Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Light-induced translocation of Pyronine G from mitochondria to nucleoli in monkey kidney CV-1 cells

    Science.gov (United States)

    Geze, Marc; Dellinger, M.; Bazin, M.; Santus, Rene C.

    1996-12-01

    Pyronine G (3,6-bis-N,N-dimethylaminoxanthylium chloride; PG) is a cationic dye that concentrates in mitochondria of living cells due to the high membrane potential of these organelles, similarly to rhodamine 123 and many other cationic dyes. Pyronine G also shows a preferential affinity for RNA. Upon light irradiation PG has been shown to induce cell death, but the photosensitizing properties of this molecule and the mechanism of cell death are not well understood. Microfluorometry and most particularly microspectrofluorometry are now powerful non-invasive techniques for quantitative studies of single living cells in real time which allow, for example, knowing how living cells are affected by photosensitization. To demonstrate the usefulness of image acquisition with high resolution and high sensitive camera, we present data on photosensitizer relocalization during illumination leading to functional and structural damage in the cells.

  18. Persistent changes in the initial rate of pyruvate transport by isolated rat liver mitochondria after preincubation with adenine nucleotides and calcium ions

    OpenAIRE

    Vaartjes, W.J.; Breejen, J.N. den; Geelen, M.J.H.; Bergh, S.G. van den

    1980-01-01

    1. Preincubation of isolated rat-liver mitochondria in the presence of adenine nucleotides or Ca2+ results in definite and persistent changes in the initial rate of pyruvate transport. 2. These changes in the rate of pyruvate transport are accompanied by equally persistent changes in the opposite direction of the activity of pyruvate dehydrogenase (EC. 1.2.4.1). 3. Changes of the transmembrane pH gradient and of the membrane potential, brought about by the pretreatments of the mitochondria, c...

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    Mingliang Li

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

  4. Developing CNS mitochondria oxidative phosphorylation P/O/ADP/O index for rats

    International Nuclear Information System (INIS)

    Egana, E.; Diaz, G.

    1975-01-01

    The effect of whole-body-gamma irradiation on developing CNS mitochondria oxidative phosphorylation was studied through the P/O/ADP/O index; three irradiation doses (5, 50 and 500 R) were employed at neonatal stage and both 'prompt' (10 min approx,) and 'delayed' (7 days for 500 R exposure, 21 days for 5 and 50 R) effects were observed. In the 'prompt' effects investigated after 500 R exposure, the oxidative phosphorylation diminished; the same occurred at 7 days with this dose ('delayed' effect). With doses of 5 and 50 R there was no alteration of oxidative phosphorylation as a 'prompt' effect, but it diminished at 21 days post irradiation. The uncoupling between respiration and oxidative phosphorylation should explain - at least, in part -these results. (author)

  5. Developing CNS mitochondria oxidative phosphorylation P/O/ADP/O index for rats

    Energy Technology Data Exchange (ETDEWEB)

    Egana, E; Diaz, G [Institute of Experimental Medicine, Santiago (Chile). Lab. of Neurochemistry

    1975-11-01

    The effect of whole-body-gamma irradiation on developing CNS mitochondria oxidative phosphorylation was studied through the P/O/ADP/O index; three irradiation doses (5, 50 and 500 R) were employed at neonatal stage and both 'prompt' (10 min approx,) and 'delayed' (7 days for 500 R exposure, 21 days for 5 and 50 R) effects were observed. In the 'prompt' effects investigated after 500 R exposure, the oxidative phosphorylation diminished; the same occurred at 7 days with this dose ('delayed' effect). With doses of 5 and 50 R there was no alteration of oxidative phosphorylation as a 'prompt' effect, but it diminished at 21 days post irradiation. The uncoupling between respiration and oxidative phosphorylation should explain - at least, in part -these results.

  6. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    International Nuclear Information System (INIS)

    Xu, Ying; Nie, Ling; Yin, Yang-Guang; Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan; Zhou, Shi-Wen

    2012-01-01

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  7. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ying [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Nie, Ling [Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Yin, Yang-Guang [Emergency Department, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhou, Shi-Wen, E-mail: Zhoushiwen1956@yahoo.cn [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)

    2012-03-15

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  8. Mangifera indica L. extract (Vimang) inhibits Fe2+-citrate-induced lipoperoxidation in isolated rat liver mitochondria.

    Science.gov (United States)

    Pardo Andreu, Gilberto; Delgado, René; Velho, Jesus; Inada, Natalia M; Curti, Carlos; Vercesi, Anibal E

    2005-05-01

    The extract of Mangifera indica L. (Vimang) is able to prevent iron mediated mitochondrial damage by means of oxidation of reduced transition metals required for the production of superoxide and hydroxyl radicals and direct free radical scavenging activity. In this study we report for the first time the iron-complexing ability of Vimang as a primary mechanism for protection of rat liver mitochondria against Fe2+ -citrate-induced lipoperoxidation. Thiobarbituric acid reactive substances (TBARS) and antimycin A-insensitive oxygen consumption were used as quantitative measures of lipoperoxidation. Vimang at 10 microM mangiferin concentration equivalent induced near-full protection against 50 microM Fe2+ -citrate-induced mitochondrial swelling and loss of mitochondrial transmembrane potential (DeltaPsi). The IC50 value for Vimang protection against Fe2+ -citrate-induced mitochondrial TBARS formation (7.89+/-1.19 microM) was around 10 times lower than that for tert-butylhydroperoxide mitochondrial induction of TBARS formation. The extract also inhibited the iron citrate induction of mitochondrial antimycin A-insensitive oxygen consumption, stimulated oxygen consumption due to Fe2+ autoxidation and prevented Fe3+ ascorbate reduction. The extracted polyphenolic compound, mainly mangiferin, could form a complex with Fe2+, accelerating Fe2+ oxidation and the formation of more stable Fe3+ -polyphenol complexes, unable to participate in Fenton-type reactions and lipoperoxidation propagation phase. The strong DPPH radical scavenging activity with an apparent IC50 of 2.45+/-0.08 microM suggests that besides its iron-complexing capacity, Vimang could also protect mitochondria from Fe2+ -citrate lipoperoxidation through direct free radical scavenging ability, mainly lipoperoxyl and alcoxyl radicals, acting as both a chain-breaking and iron-complexing antioxidant. These results are of pharmacological relevance since Vimang could be a potential candidate for antioxidant therapy in

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

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

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

  10. High resolution helium ion scanning microscopy of the rat kidney.

    Directory of Open Access Journals (Sweden)

    William L Rice

    Full Text Available Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2016-01-01

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

  13. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Hiroshi, E-mail: htomita@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574 (Japan); Tabata, Kitako, E-mail: ktabata@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Takahashi, Maki, E-mail: mqdelta@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Nishiyama, Fumiaki, E-mail: t2114018@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Sugano, Eriko, E-mail: sseriko@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan)

    2016-05-13

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  14. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    International Nuclear Information System (INIS)

    Tomita, Hiroshi; Tabata, Kitako; Takahashi, Maki; Nishiyama, Fumiaki; Sugano, Eriko

    2016-01-01

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

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

    Science.gov (United States)

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

    2000-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Hüseyin Türker

    2014-04-01

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

  18. The influence of oxazaphosphorine agents on kidney function in rats

    Directory of Open Access Journals (Sweden)

    Łukasz Dobrek

    2017-01-01

    Conclusions: CP caused more advanced kidney dysfunction and some indices suggested the development of prerenal acute kidney injury. In the CP-treated group some particularly marked urinary and plasma uric acid disturbances suggested compensation of increased oxidative stress as uric acid is considered to exert also antioxidant properties.

  19. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  20. A complex effect of arsenite on the formation of alpha-ketoglutarate in rat liver mitochondria.

    Science.gov (United States)

    Lenartowicz, E

    1990-12-01

    This investigation presents disturbances of the mitochondrial metabolism by arsenite, a hydrophilic dithiol reagent known as an inhibitor of mitochondrial alpha-keto acid dehydrogenases. Arsenite at concentrations of 0.1-1.0 mM was shown to induce a considerable oxidation of intramitochondrial NADPH, NADH, and glutathione without decreasing the mitochondrial membrane potential. The oxidation of NAD(P)H required the presence of phosphate and was sensitive to ruthenium red, but occurred without the addition of calcium salts. Mitochondrial reactions producing alpha-ketoglutarate from glutamate and isocitrate were modulated by arsenite through various mechanisms: (i) both glutamate transaminations, with oxaloacetate and with pyruvate, were inhibited by accumulating alpha-ketoglutarate; however, at low concentrations of alpha-ketoglutarate the aspartate aminotransferase reaction was stimulated due to the increase of NAD+ content; (ii) the oxidation of isocitrate was stimulated at its low concentration only, due to the oxidation of NADPH and NADH; this oxidation was prevented by concentrations of citrate or isocitrate greater than 1 mM; (iii) the conversion of isocitrate to citrate was suppressed, presumably as a result of the decrease of Mg2+ concentration in mitochondria. Thus the depletion of mitochondrial vicinal thiol groups in hydrophilic domains disturbs the mitochondrial metabolism not only by the inhibition of alpha-keto acid dehydrogenases but also by the oxidation of NAD(P)H and, possibly, by the change in the ion concentrations.

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

    Science.gov (United States)

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

    1983-01-01

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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Michał Biernacki

    2018-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Zoran Miloradović

    2014-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  6. 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....

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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)

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

    Science.gov (United States)

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

    2017-07-29

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

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

    Science.gov (United States)

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

    2012-08-01

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

  11. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huseyin Aydin Mitil

    2017-01-01

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

  14. [Role of functional state of neuronal mitochondria of cerebral cortex in mechanisms of nootropic activity of neuroprotectors in rats with alloxan hyperglycemia].

    Science.gov (United States)

    Zhiliuk, V I; Mamchur, V I; Pavlov, S V

    2015-01-01

    The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.

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

    Science.gov (United States)

    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...

  16. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

  18. 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

  19. Cardioprotective effect of hyperthyroidism on the stunned rat heart during ischaemia-reperfusion: energetics and role of mitochondria.

    Science.gov (United States)

    Ragone, María Inés; Bonazzola, Patricia; Colareda, Germán A; Consolini, Alicia E

    2015-06-01

    What is the central question of this study? Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+) handling of the postischaemic stunned heart? What is the main finding and its importance? Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia. Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'-triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c. daily with 20 μg kg(-1) triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by

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

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Stubbe, Jane; Skøtt, Ole

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hyun-Soo Kim

    2012-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  3. 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.

  4. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    International Nuclear Information System (INIS)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

    2017-01-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  5. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

    2017-05-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  6. Influence of Glucose Deprivation on Membrane Potentials of Plasma Membranes, Mitochondria and Synaptic Vesicles in Rat Brain Synaptosomes.

    Science.gov (United States)

    Hrynevich, Sviatlana V; Pekun, Tatyana G; Waseem, Tatyana V; Fedorovich, Sergei V

    2015-06-01

    Hypoglycemia can cause neuronal cell death similar to that of glutamate-induced cell death. In the present paper, we investigated the effect of glucose removal from incubation medium on changes of mitochondrial and plasma membrane potentials in rat brain synaptosomes using the fluorescent dyes DiSC3(5) and JC-1. We also monitored pH gradients in synaptic vesicles and their recycling by the fluorescent dye acridine orange. Glucose deprivation was found to cause an inhibition of K(+)-induced Ca(2+)-dependent exocytosis and a shift of mitochondrial and plasma membrane potentials to more positive values. The sensitivity of these parameters to the energy deficit caused by the removal of glucose showed the following order: mitochondrial membrane potential > plasma membrane potential > pH gradient in synaptic vesicles. The latter was almost unaffected by deprivation compared with the control. The pH-dependent dye acridine orange was used to investigate synaptic vesicle recycling. However, the compound's fluorescence was shown to be enhanced also by the mixture of mitochondrial toxins rotenone (10 µM) and oligomycin (5 µg/mL). This means that acridine orange can presumably be partially distributed in the intermembrane space of mitochondria. Glucose removal from the incubation medium resulted in a 3.7-fold raise of acridine orange response to rotenone + oligomycin suggesting a dramatic increase in the mitochondrial pH gradient. Our results suggest that the biophysical characteristics of neuronal presynaptic endings do not favor excessive non-controlled neurotransmitter release in case of hypoglycemia. The inhibition of exocytosis and the increase of the mitochondrial pH gradient, while preserving the vesicular pH gradient, are proposed as compensatory mechanisms.

  7. Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes.

    Science.gov (United States)

    González, Antonio; Pariente, José A; Salido, Ginés M

    2007-10-31

    We have employed rat hippocampal astrocytes in culture to investigate the effect of ethanol on reactive oxygen species (ROS) production as well as its effect on [Ca2+]c and GFAP expression. Cells were loaded with the fluorescent probes fura-2 and H2DCFDA for the determination of changes in [Ca2+]c and ROS production respectively, employing spectrofluorimetry. GFAP content was determined by immunocytochemistry and confocal scanning microscopy. Our results show ROS production in response to 50 mM ethanol, that was reduced in Ca2+-free medium (containing 0.5 mM EGTA) and in the presence of the intracellular Ca2+ chelator BAPTA (10 microM). The effect of ethanol on ROS production was significantly reduced in the presence of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1 mM), and the antioxidants resveratrol (100 microM) or catalase (300 U/ml). Preincubation of astrocytes in the presence of 10 microM antimycin plus 10 microM oligomycin to inhibit mitochondria completely blocked ethanol-evoked ROS production. In addition, ethanol led to a sustained increase in [Ca2+]c that reached a constant level over the prestimulation values. Finally, incubation of astrocytes in the presence of ethanol increased the content of GFAP that was significantly reduced in the absence of extracellular Ca2+ and by resveratrol and catalase pretreatment. The data obtained in the present study suggest that astrocytes are able to metabolize ethanol, which induces two effects on intracellular homeostasis: an immediate response (Ca2+ release and ROS generation) and later changes involving GFAP expression. Both effects may underline various signaling pathways which are important for cell proliferation, differentiation and function.

  8. 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.

  9. 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.

  10. 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.

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

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    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

  12. 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.

  13. Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation

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    Ahmad F

    2018-03-01

    Full Text Available Faraz Ahmad,1,2 Mohammad Salahuddin,3 Widyan Alamoudi,2 Sadananda Acharya1 1Department of Public Health, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Neuroscience Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Animal House Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia Background: Lead (Pb is a widespread environmental neurotoxin and its exposure even in minute quantities can lead to compromised neuronal functions. A developing brain is particularly vulnerable to Pb mediated toxicity and early-life exposure leads to permanent alterations in brain development and neuronal signaling and plasticity, culminating into cognitive and behavioral dysfunctions and elevated risk of neuropsychiatric disorders later in life. Nevertheless, the underlying biochemical mechanisms have not been completely discerned. Methods: Because of their ability to fulfill high energy needs and to act as calcium buffers in events of high intensity neuronal activity as well as their adaptive regulatory capability to match the requirements of the dynamicity of synaptic signaling, synapse-specific or synaptic mitochondria (SM are critical for synaptic development, function and plasticity. Our aim for the present study hence was to characterize the effects of early-life Pb exposure on the functions of SM of prepubertal rats. For this purpose, employing a chronic model of Pb neurotoxicity, we exposed rat pups perinatally and postnatally to Pb and used a plethora of colorimetric and fluorometric assays for assessing redox and bioenergetic properties of SM. In addition, taking advantage of its ability as an antioxidant and as a metal chelator, we employed ascorbic acid (vitamin C supplementation as an ameliorative therapeutic strategy against Pb-induced neurotoxicity and dysfunction of SM

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

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    Xia, Qiang; Liu, Chunxiao; Zheng, Xia

    2018-02-01

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

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2017-11-01

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

  18. 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.

  19. Electroacupuncture inhibits apoptosis in annulus fibrosis cells through suppression of the mitochondria-dependent pathway in a rat model of cervical intervertebral disc degradation

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    Jun Liao

    2012-01-01

    Full Text Available The purpose of this study was to investigate whether treatment with electroacupuncture (EA inhibited mitochondria-dependent apoptosis in annulus fibrosis (AF cells in a rat model of cervical intervertebral disc degradation induced by unbalanced dynamic and static forces. Forty Sprague-Dawley rats were used in this study, of which 30 underwent surgery to induce cervical intervertebral disc degradation, 10 rats received EA at acupoints Dazhui (DU 14 and Shousanli (LI 10. TUNEL staining was measured to assess apoptosis in AF cells, immunohistochemistry was used to examine Bcl-2 and Bax expression, colorimetric assays were used to determine caspase 9 and caspase 3 activities and RT-PCR and western blotting were used to assess the mRNA and protein expression of Crk and ERK2. Treatment with EA reduced the number of AF-positive cells in TUNEL staining, increased Bcl-2-positive cells and decreased Bax-positive cells in immunohistochemical staining, significantly inhibited the activation of caspases-9 and -3, and enhanced the mRNA and protein expression of Crk and ERK2. Our data show that EA inhibits AF cell apoptosis via the mitochondria-dependent pathway and up-regulates Crk and ERK2 expression. These results suggest that treatment with may be a good alternative therapy for preventing cervical spondylosis.

  20. 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.

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    1987-11-15

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

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

    Directory of Open Access Journals (Sweden)

    Uğur Koca

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-15

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

  13. 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)

  14. 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)

  15. 9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

    Science.gov (United States)

    Asciak, C P; Domazet, Z

    1975-02-20

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

  16. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Nisreen A. Rajeh

    2017-02-01

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

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

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Chirculescu, A R; Neagu, S

    1983-01-01

    The present paper reports on the changes occurring in the juxtaglomerular apparatus during preservation of the rat kidney by cold storage, using two media: Sacks and Plasmagel, to which a membrane stabilizing "cocktail" was added (hydrocortisone, chlorpromazine, epsilonaminocaproic acid - EACA, propranolol). Evident alterations appeared at 48 hours more accentuated at 72 and 96 hours, and more intense when preserved in Plasmagel. The most affected structure in the juxtaglomerular apparatus was the macula densa, the epithelial cells having a more stable structure.

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

    Kumar, Gurusiddaiah Suresh; Salimath, Paramahans Veerayya

    2014-01-01

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

  7. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  8. Time-dependent effect of severe hypoxia/reoxygenation on oxidative stress level, antioxidant capacity and p53 accumulation in mitochondria of rat heart

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    O. A. Gonchar

    2017-12-01

    Full Text Available The intensity of oxidative stress, protein expression of antiapoptotic Bcl-2 as well as antioxidant enzymes manganese superoxide dismutase (MnSOD and glutathione peroxidase (GPx and their regulator p53 were studied in the mitochondria of rat heart. Sessions of repeated hypoxia/reoxygenation ((H/R, 5 cycles of 10 min hypoxia (5.5% O2 in N2 alternated with 10 min normoxia, daily were performed in our study. It was shown that short-term sessions of H/R (during 1-3 days caused a significant increase in the oxidative stress markers (ROS formation and lipid peroxidation, mitochondrial p53 translocation, a decrease in MnSOD­ protein expression/activity and Bcl-2 protein content, but up-regulated GPx. We have demonstrated that prolonged H/R (7-14 days induced myocardial tolerance to fluctuation in oxygen levels that was associa­ted with the reduction in mitochondrial p53 protein content, elevation of mitochondrial Bcl-2 protein level, and increase in antioxidant capacity. A close correlation between the mitochondrial p53 accumulation and ROS formation as well as the activity and protein content of MnSOD and GPx allowed us to assume that p53 took an active part in the regulation of prooxidant/antioxidant balance in mitochondria of rat heart during repeated H/R.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Akomolafe Rufus O.

    2016-06-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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)

  14. 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.

  15. 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.

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

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

    2015-01-01

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

  17. 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

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

    Science.gov (United States)

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

    2001-05-01

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

  19. Antioxidant Protection against Pathological Mycotoxins Alterations on Proximal Tubules in Rat Kidney

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    Susan Abdu

    2011-04-01

    Full Text Available Background: Ochratoxin A (OTA was one of the mycotoxins and received attention worldwide because of the hazard it posed to human and animal health, where the kidney was the primary target organ for OTA toxicity. In the other hand, dates served as a good source of natural antioxidants and could potentially be considered as a functional food.Methods: The study was performed in the department of biology in King Abdulaziz University. Animals were gavage administrated and divided into four groups: first group received (sodium bicarbonate, second group received (289 µg OTA /kg B.W. /day, third group received (1mg Ajwa/kg B.W. / day and fourth group received (289 µg OTA /kg B.W./day+ 1mg Ajwa /kg B.W. / day. Serum (creatinine - urea levels were measured in each group at the time of tissue collection , some biopsies were fixed in 10% buffered formalin solution for light microscopy processing stained with Haematoxylin and Eosin (H& E., Periodic Acid-Schiff (PAS and Masson´s Trichrome (M.T..Other biopsies were immediately collected into electron microscopy processing. Results: After 28 days, a significant decrease in body weight, kidney weight and relative weight was detected in OTA treated group. Also, Serum (creatinine - urea level were elevated .The normal cyto-architecture of proximal tubules were lost exhibiting damaged bruch border, degenerated, binucleated and karyomegalic cells. The most destructed ultra-structure was the mitochondria which severely swollen with disintegrated membranes. In Ajwa Date extract-group the proximal tubules were normal, whereas in Ajwa date extract + OTA -group the severity of the lesions was significantly reduced. Conclusion: The present results indicated that, Ajwa date have protective effects and ameliorated the lesions of Ochratoxin nepherotoxicity which might lead to kidney failure.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-15

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-11-01

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

  4. Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression.

    Directory of Open Access Journals (Sweden)

    Anton M Markovets

    Full Text Available UNLABELLED: The incidence of age-related macular degeneration (AMD, the main cause of blindness in older patients in the developed countries, is increasing with the ageing population. At present there is no effective treatment for the prevailing geographic atrophy, dry AMD, whereas antiangiogenic therapies successful used in managing the wet form of AMD. Recently we showed that mitochondria-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1 is able to prevent the development and moreover caused regression of pre-existing signs of the retinopathy in OXYS rats, an animal model of AMD. Here we examine the effects of SkQ1 on expression of key regulators of angiogenesis vascular endothelial growth factor A (VEGF and its antagonist pigment epithelium-derived factor (PEDF genes in the retina of OXYS rats as evidenced by real-time PCR and an ELISA test for VEGF using Wistar rats as control. Ophthalmoscopic examinations confirmed that SkQ1 supplementation (from 1.5 to 3 months of age, 250 nmol/kg prevented development while eye drops SkQ1 (250 nM, from 9 to 12 months caused some reduction of retinopathy signs in OXYS rats and did not reveal any negative effects on the control Wistar rat's retina. Prevention of premature retinopathy by SkQ1 was connected with an increase of VEGF mRNA and protein in OXYS rat's retina up to the levels corresponding to the Wistar rats, and did not involve changes in PEDF expression. In contrast the treatment with SkQ1 drops caused a decrease of VEGF mRNA and protein levels and an increase in the PEDF mRNA level in the middle-aged OXYS rats, but in Wistar rats the changes of gene expression were the opposite. CONCLUSIONS: The beneficial effects of SkQ1 on retinopathy connected with normalization of expression of VEGF and PEDF in the retina of OXYS rats and depended on age of the animals and the stage of retinopathy.

  5. Oleamide synthesizing activity from rat kidney: identification as cytochrome c.

    Science.gov (United States)

    Driscoll, William J; Chaturvedi, Shalini; Mueller, Gregory P

    2007-08-03

    Oleamide (cis-9-octadecenamide) is the prototype member of an emerging class of lipid signaling molecules collectively known as the primary fatty acid amides. Current evidence suggests that oleamide participates in the biochemical mechanisms underlying the drive to sleep, thermoregulation, and antinociception. Despite the potential importance of oleamide in these physiologic processes, the biochemical pathway for its synthesis in vivo has not been established. We report here the discovery of an oleamide synthetase found in rat tissues using [(14)C]oleoyl-CoA and ammonium ion. Hydrogen peroxide was subsequently found to be a required cofactor. The enzyme displayed temperature and pH optima in the physiologic range, a remarkable resistance to proteolysis, and specificity for long-chain acyl-CoA substrates. The reaction demonstrated Michaelis-Menten kinetics with a K(m) for oleoyl-CoA of 21 microm. Proteomic, biochemical, and immunologic analyses were used to identify the source of the oleamide synthesizing activity as cytochrome c. This identification was based upon peptide mass fingerprinting of isolated synthase protein, a tight correlation between enzymatic activity and immunoreactivity for cytochrome c, and identical functional properties shared by the tissue-derived synthetase and commercially obtained cytochrome c. The ability of cytochrome c to catalyze the formation of oleamide experimentally raises the possibility that cytochrome c may mediate oleamide biosynthesis in vivo.

  6. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

    OpenAIRE

    Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

    2011-01-01

    Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Jin-jin LIU

    2013-09-01

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

  9. 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.

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

    Science.gov (United States)

    Chougule, Priti; Patil, Bhagyashree; Kanase, Aruna

    2005-06-01

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

  11. 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.).

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Sandra Villanueva

    Full Text Available The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10-18 mmHg; however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO(2 on NFAT5 activity. We found that 1 Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2 Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3 The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O(2. 4 At 2.5% of O(2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5 siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6 siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7 NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla from rats subjected to an experimental model of ischemia and reperfusion (I/R. 7 Experimental I/R increased the NFAT5-target gene aldose reductase (AR. 8 NFAT5 activators (ATM and PI3K were induced in vitro (HEK293 cells and in vivo (I/R kidneys with the same timing of NFAT5. 8 Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage.

  15. Curcumin attenuates Cr(VI)-induced ascites and changes in the activity of aconitase and F(1)F(0) ATPase and the ATP content in rat liver mitochondria.

    Science.gov (United States)

    García-Niño, Wylly Ramsés; Zazueta, Cecilia; Tapia, Edilia; Pedraza-Chaverri, José

    2014-11-01

    Occupational and environmental exposure to potassium dichromate (K2Cr2O7), a hexavalent chromium compound, can result in liver damage associated with oxidative stress and mitochondrial dysfunction. The purpose of this study was to evaluate the effect of the antioxidant curcumin (400 mg/kg b.w.) on the K2Cr2O7-induced injury, with special emphasis on ascitic fluid accumulation and oxidative phosphorylation mitochondrial enzymes and the adenosine triphosphate (ATP) levels in isolated mitochondria from livers of rats treated with K2Cr2O7 (15 mg/kg b.w.). Thus, curcumin attenuated the ascites generation, prevented the decrease in the activities of aconitase and F1F0 ATPase, and maintained the ATP levels. The activity of complex II was not completely reestablished by curcumin, whereas complexes III and IV activities were unchanged. © 2014 Wiley Periodicals, Inc.

  16. 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)

  17. 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.

  18. Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

    Directory of Open Access Journals (Sweden)

    Ali Karadeniz

    2011-01-01

    Full Text Available Cisplatin (CDDP is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg-1 body weight i.p., single dose; group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day; group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA and glutathione (GSH levels, glutathione S-transferase (GST, glutathione peroxidase (GSH-Px, and superoxide dismutase (SOD activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA, elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

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

    OpenAIRE

    Yokote, Shinya; Katsuoka, Yuichi; Yamada, Akifumi; Ohkido, Ichiro; Yokoo, Takashi

    2017-01-01

    Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced s...

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2010-12-14

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

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

    Directory of Open Access Journals (Sweden)

    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  3. Olmesartan Attenuates Tacrolimus-Induced Biochemical and Ultrastructural Changes in Rat Kidney Tissue

    Directory of Open Access Journals (Sweden)

    Naif O. Al-Harbi

    2014-01-01

    Full Text Available Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Tacrolimus significantly increased BUN and creatinine level. Treatment with olmesartan reversed tacrolimus-induced changes in the biochemical markers (BUN and creatinine of nephrotoxicity. Tacrolimus significantly decreased GSH level and catalase activity while increasing MDA level. Olmesartan also attenuated the effects of tacrolimus on MDA, GSH, and catalase. In tacrolimus group histological examination showed marked changes in renal tubule, mitochondria, and podocyte processes. Histopathological and ultrastructural studies showed that treatment with olmesartan prevented tacrolimus-induced renal damage. These results suggest that olmesartan has protective effects on tacrolimus-induced nephrotoxicity, implying that RAS might be playing role in tacrolimus-induced nephrotoxicity.

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

    Science.gov (United States)

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

    2007-11-01

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

  5. Your mitochondria are what you eat

    DEFF Research Database (Denmark)

    Jørgensen, Wenche; Rud, Kasper Abildgaard; Mortensen, Ole Hartvig

    2017-01-01

    of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randle‐type fat‐carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux‐ratio: pyruvate dehydrogenase (PDH)/β‐oxidation to suit...... the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate‐fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for 12 weeks to a HF‐ or a HS diet as compared to rats given...... a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

    Directory of Open Access Journals (Sweden)

    Ayodele Jacob Akinyemi

    2017-04-01

    Full Text Available In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6: saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05. However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO. However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

  8. 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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-09-08

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

  12. Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidence by autoradiography

    International Nuclear Information System (INIS)

    Bouizar, Z.; Rostene, W.H.; Milhaud, G.

    1987-01-01

    In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with 125 I-labeled sCT. Autoradiograms demonstrated a heterogeneous distribution of 125 I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert it physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Aging and mitochondria.

    Science.gov (United States)

    Gadaleta, M N; Cormio, A; Pesce, V; Lezza, A M; Cantatore, P

    1998-10-01

    Aging is a complex physiological phenomenon and several different theories have been elaborated about its origin. Among such theories, the 'mitochondrial theory of aging', which has gained a large support, indicates the accumulation of somatic mutations of mitochondrial DNA leading to the decline of mitochondrial functionality as one of the driving forces for the process itself. In this review data on rat and man from our laboratory and from recent literature have been thoroughly examined and compared in order to provide the 'state-of-the-art' on the role of mitochondria in aging. Alterations of structure and expression of mitochondrial genome with aging, to find out the eventual relevant changes of mitochondrial biogenesis, have been studied in rat whereas the relationship between cytochrome c oxidase activity and 'common deletion' has been studied in man. Results on the effect of acetyl-L-carnitine on the mitochondrial functionality are also reported.

  19. 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.

  20. 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.

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

    Science.gov (United States)

    Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

    2008-01-01

    The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

  2. 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.

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

    Science.gov (United States)

    Golshan, Alireza; Hayatdavoudi, Parichehr; Hadjzadeh, Mousa Al-Reza; Khajavi Rad, Abolfazl; Mohamadian Roshan, Nema; Abbasnezhad, Abbasali; Mousavi, Seyed Mojtaba; Pakdel, Roghayeh; Zarei, Batool; Aghaee, Azita

    2017-01-01

    The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon ( C. dactylon ) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper. Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining. Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon , lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05). A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.

  4. Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

    OpenAIRE

    Takakura, Kentaro; Ito, Shogo; Sonoda, Junya; Tabata, Koji; Shiozaki, Motoko; Nagai, Kaoru; Shibata, Masahiro; Koike, Masato; Uchiyama, Yasuo; Gotow, Takahiro

    2017-01-01

    The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to â¼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of ...

  5. Evidence for two compartments of exchangeable calcium in isolated rat liver mitochondria obtained using a 45Ca exchange technique in the presence of magnesium, phosphate, and ATPase at 370C

    International Nuclear Information System (INIS)

    Barritt, G.J.

    1981-01-01

    The distribution of calcium between isolated rat liver mitochondria and the extramitochondrial medium at 37 degrees C and in the presence of 2 mM inorganic phosphate, 3 mM ATP, 0.05 or 1.1 mM free magnesium and a calcium buffer, nitrilotriacetic acid, was investigated using a 45 Ca exchange technique. The amounts of 40 Ca in the mitochondria and medium were allowed to reach equilibrium before initiation of the measurement of 45 Ca exchange. At 0.05 mM free magnesium and initial extramitochondrial free calcium concentrations of between 0.15 and 0.5 microM, the mitochondria accumulated calcium until the extramitochondrial free calcium concentration was reduced to 0.15 microM. Control experiments showed that the mitochondria were stable under the incubation conditions employed. The 45 Ca exchange data were found to be consistent with a system in which two compartments of exchangeable calcium are associated with the mitochondria. Changes in the concentration of inorganic phosphate did not significantly affect the 45 Ca exchange curves, whereas an increase in the concentration of free magnesium inhibited exchange. The maximum rate of calcium outflow from the mitochondria was estimated to be 1.7 nmol/min per mg of protein, and the value of K0.5 for intramitochondrial exchangeable calcium to be about 1.6 nmol per mg of protein. Ruthenium Red decreased the fractional transfer rate for calcium inflow to the mitochondria while nupercaine affected principally the fractional transfer rates for the transfer of calcium between the two mitochondrial compartments. The use of the incubation conditions and 45 Ca exchange technique described in this report for studies of the effects of agents which may alter mitochondrial calcium uptake or release (e.g., the pre-treatment of cells with hormones) is briefly discussed

  6. Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes.

    Science.gov (United States)

    Liu, Xue-Ru; Cao, Lu; Li, Tao; Chen, Lin-Lin; Yu, Yi-Yan; Huang, Wen-Jun; Liu, Li; Tan, Xiao-Qiu

    2017-05-01

    Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H 2 O 2 at 500 μM (H 2 O 2 group), propofol at 50 μM (propofol group), and H 2 O 2 plus propofol (H 2 O 2  + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H 2 O 2 -induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H 2 O 2 -induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H 2 O 2 -induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H 2 O 2 -induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.

  7. Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI).

    Science.gov (United States)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-03-01

    Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism based inhibition of ATP synthesis is exerted by diclofenac and its metabolites. Phase-I metabolite (4'-OH-Dic) and Phase-II metabolites (DicGluA and DicSG) showed potent inhibition (2-5 fold) of ATP synthesis, where as 5-OH-Dic, one of the Phase-I metabolite, was a less potent inhibitor as compared to Dic. The calculated kinetic constants of mechanism based inhibition of ATP synthesis by Dic showed maximal rate of inactivation (Kinact) of 2.64 ± 0.15 min(-1) and half maximal rate of inactivation (KI) of 7.69 ± 2.48 μM with Kinact/KI ratio of 0.343 min(-1) μM(-1). Co-incubation of mitochondria with Dic and reduced GSH exhibited a protective effect on Dic mediated inhibition of ATP synthesis. Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sheila Marques Fernandes

    2016-01-01

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

  14. Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Bartlomiej Kalaska

    2017-10-01

    Full Text Available The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone

  15. Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: differences in mitochondria.

    Science.gov (United States)

    Harada, K; Endo, Y; Warashina, A; Inoue, M

    2015-08-20

    The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. 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:

  17. 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

  18. 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

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

    Science.gov (United States)

    Apaydın, Fatma Gökçe; Baş, Hatice; Kalender, Suna; Kalender, Yusuf

    2016-01-01

    Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Inhibition of calcium oxalate crystal deposition on kidneys of urolithiatic rats by Hibiscus sabdariffa L. extract.

    Science.gov (United States)

    Laikangbam, Reena; Damayanti Devi, M

    2012-06-01

    The present study aims at systematic evaluation of the calyces of Hibiscus sabdariffa to establish its scientific validity for anti-urolithiatic property using ethylene glycol-induced hyperoxaluria model in male albino rats. Administration of a mixture of 0.75% ethylene glycol and 2% ammonium chloride resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. The decrease in the serum calcium concentration indicates an increased calcium oxalate formation. Supplementation of aqueous extract of H. sabdariffa at different doses (250, 500 and 750 mg/kg body weight) significantly lowered the deposition of stone-forming constituents in the kidneys and serum of urolithiatic rats. These findings have been confirmed through histological investigations. Results of in vivo genotoxicity testing showed no significant chromosomal aberrations in the bone marrow cells of ethylene glycol-induced rats. The plant extracts at the doses investigated induced neither toxic nor lethal effects and are safe. It can be concluded that the calyces of H. sabdariffa are endowed with anti-urolithiatic activity and do not have genotoxic effects. Thus, it can be introduced in clinical practices and medicine in the form of orally administered syrup after further investigations and clinical trials.

  1. Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Sivaprasad, R.; Nagaraj, M.; Varalakshmi, P. [Department of Medical Biochemistry, University of Madras (Taramani), Chennai 600 113 (India)

    2002-08-01

    The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-{alpha}-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of {gamma}-glutamyl transferase and N-acetyl {beta}-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell. (orig.)

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-03-31

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

  5. Protonmotive force in muscle mitochondria

    International Nuclear Information System (INIS)

    Stumpf, D.A.; Haas, R.; Eguren, L.A.; Parks, J.K.; Eilert, R.E.

    1982-01-01

    The protonmotive force (delta p) of muscle mitochondria was measured by estimating the distribution of 14C-labeled TPMP (trimethylphenylphosphonium iodide) and 14C-labeled acetate across the inner membrane of muscle mitochondria. The matrix volume was simultaneously determined using 3H-labeled H2O and 3H-labeled mannitol and repeated drying to distinguish the label in these 2 compounds. Rapid separation of mitochondria from the incubation medium by centrifugation through silicone oil avoids the problems of potential anaerobic conditions associated with conventional centrifugation and large volumes of trapped media associated with filtration. The value for delta p (mean +/- SD) was 192+/- 26 mV in 30 determinations with rat muscle mitochondria during state 4. Measurement of oxygen consumption allowed calculation of membrane conductance (Cm,H+) which was 0.49 +/- 0.18 nmol of H+/min/mg protein/mV. The values for delta p and Cm,H+ are reported for a variety of experimental conditions and are consistent with Mitchell's chemiosmotic theory. Biopsy specimens obtained from human muscle gave state-4 delta p values of 197+/- 30 mV (n .5) and Cm,H+ values of 0.52 +/- 0.12 nmol of H+/min/mg/mV (n . 4). This delta p assay is the first described for coupled mammalian muscle mitochondria and will be useful in assessing membrane function

  6. Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria

    Czech Academy of Sciences Publication Activity Database

    Wasková-Arnoštová, P.; Elsnicová, B.; Kašparová, D.; Horníková, D.; Kolář, František; Novotný, J.; Žurmanová, J.

    2015-01-01

    Roč. 119, č. 12 (2015), s. 1487-1493 ISSN 8750-7587 Institutional support: RVO:67985823 Keywords : hexokinase * mitochondrial colocalization * cardioprotection * chronic hypoxia * rat heart Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.004, year: 2015

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

    Science.gov (United States)

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

    2003-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Chung-Kan Peng

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

  9. 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.

  10. Morphological aspects of the rat kidney preserved by cold storage. IV. Histoenzymological changes. V. Endopeptidase activity.

    Science.gov (United States)

    Neagu, S; Bandu, C; Chirculescu, A R; Codorean, E; Cuida, I; Gabrielescu, E

    1984-01-01

    Rat kidneys were preserved by initial washing and cooling perfusion, followed by cold storage at 6 degrees C for 24, 48, 72 and 96 hours, in two different media: Sacks (hyperosmolar electrolytic solution of intracellular type) and Plasmagel (gelation solution 4%). Evidence was found of DPNH-diaphorase, lactate dehydrogenase (LDH), leucylaminopeptidase (LAP) and adenosine-triphosphatase (ATPase) (pH 9.4) activities. Histoenzymological determination showed various levels of enzymatic activities in different segments of the nephron, levels relatively well maintained during storage, even at 72 and 96 hours. At the same time, cathepsin B and D and neutral proteinase activities were determined as parameters of maintained cellular enzymatic activity; different aspects were observed with the two preservation media used.

  11. Simple radioisotopic technique for the study of urate transport in the rat kidney

    International Nuclear Information System (INIS)

    Abramson, R.G.; Levitt, M.F.; Maesaka, J.K.; Katz, J.H.

    1974-01-01

    To study uric acid transport in single nephrons and whole kidney of the rat, a technique has been developed for the radioassay of uric acid-2- 14 C in plasma, urine, and tubular fluid. Labeled allantoin, which results from the in vivo oxidation of uric acid-2- 14 C, is readily separated from the labeled uric acid by a two-step elution from a strongly basic anion exchange resin using column chromatography. It is concluded that this radioassay is a valid technique and that it provides a more sensitive and precise means of measuring U/P uric acid ratios at endogenous plasma uric acid concentrations than does a conventional differential spectrophotometric method

  12. Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Lipsø, Hans Kasper Wigh; Østergaard, Jakob Appel

    2014-01-01

    with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which...... administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization...... and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates...

  13. Time- and sequence-dependent responses to cisplatin and radiation in the rat kidney

    International Nuclear Information System (INIS)

    Rongen, Eric van; Kuijpers, W.C.; Baten-Wittwer, Andrea

    1991-01-01

    The influence of time interval and sequence between administration of cisplatin and a radiation dose was studied in the rat kidney. Changes in glomerular function were only detected after 30 weeks following the higher drug dose (6.0 mg/kg). X-rays alone caused measurable alterations in both glomerular and tubular function after 16 weeks. In the combined treatment the influence of time and sequence was significant. If cisplatin was given at 7 to 1 days before X-rays the effect of time was minimal. Administration of cisplatin 12 h to 15 min before irradiation resulted in an increase of radiation damage with decreasing time interval. Total damage sharply decreased when both modalities were given at the same time, and decreased further with increasing time between irradiation and drug administration. (author)

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  15. DNA methylation analysis in rat kidney epithelial cells exposed to 3-MCPD and glycidol.

    Science.gov (United States)

    Senyildiz, Mine; Alpertunga, Buket; Ozden, Sibel

    2017-10-01

    3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been regarded as a rat carcinogen, which is known to induce Leydig-cell and mammary gland tumors in males, as well as kidney tumors in both genders. 3-MCPD is highly suspected to be a non-genotoxic carcinogen. 2,3-Epoxy-1-propanol (glycidol) can be formed via dehalogenation from 3-MCPD. We aimed to investigate the cytotoxic effects of 3-MCPD and glycidol, then to demonstrate the possible epigenetic mechanisms with global and gene-specific DNA methylation in rat kidney epithelial cells (NRK-52E). IC 50 value of 3-MCPD was determined as 48 mM and 41.39 mM, whereas IC 50 value of glycidol was 1.67 mM and 1.13 mM by MTT and NRU test, respectively. Decreased global DNA methylation at the concentrations of 100 μM and 1000 μM for 3-MCPD and 100 μM and 500 μM for glycidol were observed after 48 h exposure by using 5-methylcytosine (5-mC) ELISA kit. Methylation changes were detected in promoter regions of c-myc and Rassf1a in 3-MCPD and glycidol treated NRK-52E cells by using methylation-specific PCR (MSP), whereas changes on gene expression of c-myc and Rassf1a were observed by using real-time PCR. However, e-cadherin, p16, VHL and p15 genes were unmethylated in their CpG promoter regions in response to treatment with 3-MCPD and glycidol. Alterations in DNA methylation might be key events in the toxicity of 3-MCPD and glycidol.

  16. Beneficial Effect of Moderate Exercise in Kidney of Rat after Chronic Consumption of Cola Drinks.

    Directory of Open Access Journals (Sweden)

    Gabriel Cao

    Full Text Available The purpose of this study was to investigate the effect of moderate intensity exercise on kidney in an animal model of high consumption of cola soft drinks.Forty-eight Wistar Kyoto rats (age: 16 weeks; weight: 350-400 g were assigned to the following groups: WR (water runners drank water and submitted to aerobic exercise; CR (cola runners drank cola and submitted to aerobic exercise; WS (water sedentary and CS (cola sedentary, not exercised groups. The aerobic exercise was performed for 5 days per week throughout the study (24 weeks and the exercise intensity was gradually increased during the first 8 weeks until it reached 20 meters / minute for 30 minutes. Body weight, lipid profile, glycemia, plasma creatinine levels, atherogenic index of plasma (AIP and systolic blood pressure (SBP were determined. After 6 months all rats were sacrificed. A kidney histopathological score was obtained using a semiquantitative scale. Glomerular size and glomerulosclerosis were estimated by point-counting. The oxidative stress and pro-inflammatory status were explored by immunohistochemistry. A one way analysis of variance (ANOVA with Tukey-Kramer post-hoc test or the Kruskal-Wallis test with Dunn's post-hoc test was used for statistics. A value of p < 0.05 was considered significant.At 6 months, an increased consumption of cola soft drink was shown in CS and CR compared with water consumers (p<0.0001. Chronic cola consumption was associated with increased plasma triglycerides, AIP, heart rate, histopathological score, glomerulosclerosis, oxidative stress and pro-inflammatory status. On the other hand, moderate exercise prevented these findings. No difference was observed in the body weight, SBP, glycemia, cholesterol and plasma creatinine levels across experimental groups.This study warns about the consequences of chronic consumption of cola drinks on lipid metabolism, especially regarding renal health. Additionally, these findings emphasize the protective

  17. Melatonin Protects the Heart, Lungs and Kidneys from Oxidative Stress under Intermittent Hypobaric Hypoxia in Rats

    Directory of Open Access Journals (Sweden)

    Jorge G Farías

    2012-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidney, and of the reproductive system, such as testis and epididymis in animals exposed to intermittent hypobaric hypoxia and therefore exposed to oxidative stress and analyzed by lipid peroxidation. Ten-week-old male Wistar rats were divided into 6 groups for 96 hours during 32 days under: 1 Normobaric conditions, 2 plus physiologic solution, 3 plus melatonin, 4 intermittent hypobaric hypoxia, 5 plus physiologic solution and 6 plus melatonin. The animals were injected with melatonin (10 mg/kg body weight at an interval of 96 hours during 32 days. Results indicated that melatonin decreased lipid peroxidation in heart, kidneys and lung under intermittent hypobaric hypoxia conditions. However, it did not exhibit any protective effect in liver, testis, epididymis and sperm count.

  18. Effect of administering a diet contamined with fumonisins on the kidneys of wistar rats

    Directory of Open Access Journals (Sweden)

    Jade Cabestre Venancio

    2014-08-01

    Full Text Available Fumonisins (FBs are mycotoxins produced by Fusarium molds. Several works have shown contamination of maize by this toxin. Fumonisin B1 (FB-1 is found in greatest proportion (about 70%, resistant to several industrialization processes. In that context, the objective of this work was to analyze the effect of administering a diet contaminated with FB-1 on the morphophysiology of the kidneys of 21-day old male Wistar rats. The animals were divided into 2 groups: G0 (with animals receiving feed free of FBs and G6 (6mg of FB1 kg-1 of feed. The diet was administered during 42 days. After that period, the animals were placed in metabolic cages for urine collection, blood was collected for analysis of plasma creatinine, and the kidneys were fixed and stained with Masson's trichrome. We observed that FB1 administration did not affect feed intake, body weight gain and animal growth. The normal levels of plasma creatinine suggest that the toxin did not lead to glomerular lesion. There was also no change in water intake, osmolarity and excretion of sodium in urine. However, there was a significant increase in urine volume and potassium excretion in urine, with mild tubulointerstitial changes in the outer cortex for the group receiving the mycotoxin.

  19. Right ventricular pressure elevated in one-kidney, one clip Goldblatt hypertensive rats.

    Science.gov (United States)

    Ketabchi, Farzaneh; Bajoovand, Shirin; Adlband, Mojtaba; Naseh, Maryam; Nekooeian, Ali A; Mashghoolozekr, Elaheh

    2017-01-01

    Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways.

  20. Varying effects of calcium on the oxidation of palmitate and alpha-ketoglutarate in isolated rat liver mitochondria incubated in KCl-based and sucrose-based media.

    Science.gov (United States)

    Borrebaek, B; Dolva, K; Singh, B

    1984-01-01

    Isolated mitochondria from rat liver were incubated in the presence of [U-14C]palmitate, ATP, CoA, carnitine, EGTA (ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid) and varying amounts of calcium. When a KC1-based incubation medium was used, the oxidation of palmitate was inhibited when the concentration of free calcium was increased from about 0.1-10 microM. When a sucrose-based incubation medium was used, the basal rate of palmitate oxidation was about half of that observed with the KC1-medium and calcium had a stimulatory effect. With the KC1-medium the rate of oxygen consumption was inhibited by calcium with alpha-ketoglutarate as well as palmitate as the respiratory substrate. No inhibitory effect of calcium was observed with succinate or beta-hydroxybutyrate. With the KC1-medium and with alpha-ketoglutarate as the respiratory substrate, state 3 respiration but not state 4 respiration was inhibited by calcium. When the sucrose-medium was used, state 3 respiration was first inhibited by calcium, but this inhibition was gradually relieved and the respiratory rate finally became higher than it was before calcium addition.

  1. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    International Nuclear Information System (INIS)

    Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

    2013-01-01

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary

  2. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2007-11-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Sumaira Sahreen

    2015-09-01

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

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

    Science.gov (United States)

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

    2014-05-27

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

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

    Directory of Open Access Journals (Sweden)

    Sarah Engeham

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  10. Safety Profile of Meswak Root Extract on Liver, Kidney, Sexual Hormones and Hematological Parameters of Rats

    Directory of Open Access Journals (Sweden)

    Abeer Y. IBRAHIM

    2012-02-01

    Full Text Available This study was conducted to investigate the safety profile of Salvadora persica (Salvadoraceae aqueous alcoholic root extract by carrying out acute and sub-chronic toxicity assessment in order to find out any side effect of the traditionally using of these root sticks. Regarding to acute toxicity test, mice were administered the extract up to 5 g kg-1, intraperitoneally. Animals were then observed for behavioural changes; signs of toxicity, and mortality within 24 h. Surviving mice were monitored for 7 days for signs of delayed toxicity. In the sub-chronic toxicity test, rats were daily treated with the extract at a dose of 400 mg kg-1 intraperitoneally, for 30 days. At the end of the test period, hematological and biochemical parameters were determined in blood and serum samples with determination of vital organs weights. In the acute toxicity test, the extract was practically non-toxic showing no mortality and visible signs of delayed toxicity. The LD50, given intraperitoneally, was estimated to be 4 g kg-1. Administration of extract (at a dose of 400 mg Kg-1 b.wt. to male and female rats for 30 days did not produce any significant (P < 0.05 effect on hematological and most biochemical parameters also vital organs weights. The root extract showed adverse effects on sexual hormones, by increasing estrogen secretion and reducing testosterone level in male rats. At the same time, the extract reduces progesterone level in female satellite group. Overall, Meswak aqueous extract is safe concerning liver and kidney functions and hematological assessments; however, it induces reversal effect on sexual hormones levels determined in sera.

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

    Science.gov (United States)

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

    2017-05-01

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

  12. Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Quistorff, Bjørn

    2008-01-01

    ADP is generally accepted as a key regulator of oxygen consumption both in isolated mitochondria and in permeabilized fibers from skeletal muscle. The present study explored inorganic phosphate in a similar regulatory role. Saponin permeabilized fibers and isolated mitochondria from type-I and type...

  13. Data on effects of rotenone on calcium retention capacity, respiration and activities of respiratory chain complexes I and II in isolated rat brain mitochondria

    Directory of Open Access Journals (Sweden)

    Evelina Rekuviene

    2017-08-01

    Full Text Available The data presented in this article are related to the research article entitled “Rotenone decreases ischemia-induced injury by inhibiting mitochondrial permeability transition in mature brains” (Rekuviene et al., 2017 [1]. Data in this article present the direct effects of rotenone on calcium retention capacity (CRC in isolated normal cortex and cerebellum mitochondria, effects of rotenone intravenous infusion on leak and phosphorylating respiration rates of isolated cortex and cerebellum mitochondria, on activities of respiratory chain complexes I and II in freezed-thawed/sonicated cortex and cerebellum mitochondria after brain ischemia. In addition, detailed experimental procedures of isolation of brain mitochondria, measurements of CRC, respiration, activities of respiratory chain complexes and H2O2 generation in cortex and cerebellum mitochondria are described.

  14. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1980-12-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  17. 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...

  18. 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...

  19. D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

    2013-02-15

    Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative stress

  20. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    International Nuclear Information System (INIS)

    Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

    2013-01-01

    The maintenance of extracellular Na + and Cl - concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na + and Cl - reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg -1 ·day -1 , sc) and progesterone (OVP, 1.7 mg·kg -1 ·day -1 , sc). We assessed Na + and Cl - fractional excretion (FE Na + and FE Cl - , respectively) and renal and plasma catecholamine release concentrations. FE Na + , FE Cl - , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE Na + , FE Cl - , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function

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

    Science.gov (United States)

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

    2016-12-20

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    EI-Tawil, G A [Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2009-07-01

    Whole body exposure to ionizing radiation provokes oxidative damage, organ dysfunction and metabolic disturbances. Fenugreek (Trigonella foenumgraecum L. Leguminosae), one of the oldest medicinal plants rich in polyphenolic compounds is known to possess antioxidant properties. The present study was designed to determine the possible protective effect of fenugreek, against {gamma}-radiation-induced oxidative stress in liver and kidney tissues of rats. In parallel, the alteration in the activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as markers of liver function, creatinine and urea levels as markers of kidney function. In addition, serum glucose and insulin levels were determined as markers for carbohydrate metabolism. Irradiated rats were whole body exposed to 3.5 Gy (Acute dose) {gamma}-radiations. Fenugreek-treated irradiated rats received 1g fenugreek seed powder/kg body weight/day, by gavages, during 7 days before irradiation. Animals were sacrificed on the 1 sl day after irradiation. The results obtained demonstrated that exposure to ionizing radiation induced significant decreases in SOD and CAT activities and GSH content associated to significant increase of TBARS levels in liver and kidney. Fenugreek treatment has significantly attenuated radiation-induced oxidative stress in both tissues, which was substantiated by the significant amelioration of serum ALP, AST and ALT activities, creatinine, urea, glucose, and insulin levels. It could be concluded that fenugreek would protect from oxidative damage and metabolic disturbances induced by ionizing irradiation.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Kerstin Stemmer

    2012-09-01

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

  8. Characterization of amino acid metabolism by cultured rat kidney cells: Study with 15N

    International Nuclear Information System (INIS)

    Nissim, I.; States, B.; Yudkoff, M.; Segal, S.

    1987-01-01

    The present study evaluates the metabolism of glutamine and glutamate by normal rat kidney (NRK) cells. The major aim was to evaluate the effect of acute acidosis on the metabolism of amino acid and ammonia formation by cultured NRK cells. Experiments at either pH 7.0 or 7.4 were conducted with phosphate-buffered saline supplemented with either 1 mM [5- 15 N]glutamine, [2- 15 N]glutamine, or [ 15 N]glutamate. Incubation with either glutamine or glutamate as a precursor showed that production of ammonia and glucose was increased significantly at pH 7.0 vs 7.4. In experiments with [5- 15 N]glutamine, the authors found that ∼57 and 43% of ammonia N was derived from 5-N of glutamine at pH 7.4 and 7.0, respectively. Three major metabolic pathways of [2- 15 N]glutamine or [ 15 N]glutamate disposal were identified: (1) transamination reactions involving the pH-independent formation of [ 15 N] aspartate and [ 15 N]alanine; (2) the synthesis of [6- 15 NH 2 ]adenine nucleotide, a process more active at pH 7.4 vs. 7.0; and (3) glutamine synthesis from [ 15 N]glutamate, especially at pH 7.4. The data indicate that NRK cells in culture consume glutamine and glutamate and generate ammonia and various amino acids, depending on the H + concentration in the media. The studies suggest that these cell lines may provide a useful model for studying various aspects of the effect of pH on rat renal ammoniagenesis

  9. Impact of Isotretinoin on The Liver and Kidney of Irradiated Pregnant Rats and Their Fetuses

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Ismail, N.H.

    2011-01-01

    This study aimed to evaluate the impact of isotretinoin and/or gamma radiation on the pregnant rats and their fetuses as judged by the maternal biochemical, histochemical and histopathological lesions induced in their fetuses. Isotretinoin (13-cis-retinoic acid) is related to both retinoic acid and retinol (vitamin A) and found in small natural quantities in liver. It is medically indicated for treatment of severe cytic acne vulgaris. Isotretinoin at a dose level of 30 mg/kg was daily administered orally to pregnant albino rats from the 5th to 10th day of gestation. Mothers were subjected to 1 Gy of gamma radiation (0.5 Gy each time) on the 6th and 9th days of gestation then investigations were carried out on 20th day of gestation. The data obtained revealed that isotretinoin administration and/or gamma radiation exposure caused significant increase in maternal serum levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C), glucose, alanine and aspartate transaminases (AST, ALT) and creatinine (Cr) . In addition to decreased levels of serum protein, gamma, beta, alpha 2, alpha 1 and albumin with concomitance increase in pre-albumin were observed. The histopathological results of the liver tissue showed different distortions, which varied from necrotic cells, such as loss of architecture of hepatic lobules, rupture of the walls of blood vessels, dilated and congested blood vessels and vacuolated cytoplasm of the liver cells. On the other hand, the kidney tissue showed thickness of Bowman's capsule with hyaline material, atrophic glomerular tufts, fragmentlysis convoluted and completely degeneration of renal tubules. In addition, the histochemical observations revealed diminutions in each of the polysaccharides and DNA contents. It could be concluded that isotretinoin intake and/or radiation exposure could exert deleterious effect, therefore, radiation occupational workers, especially females, have to be careful toward isotretinoin intake

  10. 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

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

    International Nuclear Information System (INIS)

    Sun Junhui; Teng Gaojun; Ju Shenghong; Ma Zhanlong; Mai Xiaoli; Zhang Yu; Ma Ming

    2006-01-01

    Objective: To evaluate in vivo depiction and tracking for magnetically labeled bone marrow mesenchymal stern cells (MSCs) in a renal failure rat model injected intravascularly using a 1.5 T magnetic resonance imaging (MRI) system. Methods: Rat MSCs were isolated, purified, expanded and then incubated with home synthesized Fe 2 O 3 -PLL. Prussian blue stain was employed for identifying intracellular irons. An acute renal failure in rat was induced by intramuscular injection of glycerol and MSCs were injected into renal arteries of 11 recipients (labeled cells in six, unlabeled cells in five). MR images of kidneys were obtained respectively before injection of MSCs, and immediately, 1, 3, 5, and 8 clays after transplantation. MR imaging findings were analyzed, which were correlated with histological findings. Results: Rat MSCs were successfully labeled, and labeling efficiency was almost 100%. Prussian blue staining of Fe 2 O 3 -PLL labeled cells revealed the presence of iron-containing vesicles or endosomes in the cytoplasm. In the renal failure model of rats, the labeled MSCs were demonstrated as signal intensity loss in renal cortex on T 2 * -weighted MR images. The signal intensity decrease was visualized up to days 8 after transplantation. Histological analyses showed that most Prussian blue staining-positive cells were well correlated with the area where a signal intensity loss was observed in MRI. Signal intensity decrease was not detected after transplantation of unlabeled cells. Conclusion: The rat MSCs can be effectively labeled with Fe 2 O 3 -PLL. 1.5-T MR imaging seems to be a good technique to monitor the magnetically labeled MSCs in vivo in renal failure rat model intravascularly administered, which may have much more potential values for studying the engraftment of stem cells in kidneys. (authors)

  12. Melatonin, mitochondria and hypertension.

    Science.gov (United States)

    Baltatu, Ovidiu C; Amaral, Fernanda G; Campos, Luciana A; Cipolla-Neto, Jose

    2017-11-01

    Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin-angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin-angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

  13. Thiazide diuretic receptors: Autoradiographic localization in rat kidney with [3H]metolazone

    International Nuclear Information System (INIS)

    Beaumont, K.; Vaughn, D.A.; Healy, D.P.

    1989-01-01

    The localization of binding sites for [ 3 H]metolazone, a quinazolinesulfonamide diuretic with thiazide-like actions, was determined by in vitro autoradiography. [ 3 H]Metolazone bound saturably to rat kidney sections incubated in vitro with a dissociation constant (Kd) = 3.4 nM and binding site density = 0.14 pmol/mg of protein. Incubation conditions were used that excluded binding to low affinity sites and carbonic anhydrase. Pharmacological specificity of binding was consistent with labeling of physiologically relevant thiazide diuretic receptors, as identified in previous studies of [ 3 H]metolazone binding to renal membranes. Autoradiographs obtained with tritium-sensitive film demonstrated that binding sites were limited to the renal cortex and were relatively sparsely distributed. Higher resolution autoradiography indicated that [ 3 H] metolazone binding sites were localized in a highly specific manner over short lengths of tubular segments, which by their morphology and distribution most likely represented distal convoluted tubules. In the short sections of tubule that contained receptors, labeling was very dense and appeared to be more prevalent over luminal than peritubular surfaces. The intrarenal distribution of [ 3 H]metolazone binding sites provides further evidence for their identity as thiazide diuretic receptors. These results are consistent with physiological studies demonstrating that the early distal tubule is the location of thiazide-sensitive sodium chloride cotransport

  14. 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.

  15. 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

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

    International Nuclear Information System (INIS)

    Zacikova, L.

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K. [Heidelberg Univ., Mannheim (Germany). Dept. of Medicine V

    2017-05-01

    To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

  18. 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.

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

    Science.gov (United States)

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

    2018-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Paweł Bodera

    2015-08-01

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

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

    International Nuclear Information System (INIS)

    Verbaeys, A.; Maele, G. van; Sy, W. de; Ringoir, S.; Lameire, N.; University Hospital, Ghent; University Hospital, Ghent

    1991-01-01

    Water soluble ionic contrast media (CM) and glucose 5% were administered to Sprague-Dawley rats 36 hours after bilateral warm renal ischemia for 45 min. In all animals (n=28) the renal ischemia caused a decrease of the absolute urinary creatinine output. Intraarterial injection of glucose 5% or CM did not produce different patterns of absolute urinary creatinine output. The serum creatinine increased after 36 hours of reflow. When compared by means of a Mann-Whitney U-test to a normal median serum creatinine obtained in a separate group of 22 normal rats, the increase was statistically significant (p≤0.01). The serum creatinine medians returned to a normal level after 24 hours. It seems therefore that 45 min of warm renal ischemia and 36 hours of reflow is an insufficient challenge to the rat kidney for the detection of the nephrotoxic properties of CM as opposed to when CM are injected during ischemia. (orig.)

  2. Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

    DEFF Research Database (Denmark)

    Patel, Sanket N; Ali, Quaisar; Samuel, Preethi

    2017-01-01

    The actions of angiotensin II type 2 receptor (AT2R) and the receptor Mas (MasR) are complex but show similar pronatriuretic function; particularly, AT2R expression and natriuretic function are enhanced in obese/diabetic rat kidney. In light of some reports suggesting a potential positive...... interaction between these receptors, we tested hypothesis that renal AT2R and MasR physically interact and are interdependent to stimulate cell signaling and promote natriuresis in obese rats. We found that infusion of AT2R agonist C21 in obese Zucker rats (OZR) increased urine flow and urinary Na excretion...... coimmunoprecipitated with MasR in cortical homogenate of OZR. Immunoblotting of cortical homogenate cross-linked with zero-length oxidative (sulfhydryl groups) cross-linker cupric-phenanthroline revealed a shift of AT2R and MasR bands upward with overlapping migration for their complexes which were sensitive...

  3. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Science.gov (United States)

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  4. 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

  5. Taurine Supplementation Alleviates Puromycin Aminonucleoside Damage by Modulating Endoplasmic Reticulum Stress and Mitochondrial-Related Apoptosis in Rat Kidney

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2018-05-01

    Full Text Available Taurine (TAU is a sulfur-containing beta amino acid that is not involved in protein composition and anabolism, conditionally essential in mammals provided through diet. Growing evidence supports a protective role of TAU supply in osmoregulation, calcium flux, and reduction of inflammation and oxidant damage in renal diseases like diabetes. Endoplasmic reticulum (ER stress, due to abnormal proteostasis, is a contributor to nephrotic syndrome and related renal damage. Here, we investigated the effect of dietary TAU (1.5% in drinking water for 15 days in an established rat model that mimics human minimal change nephrosis, consisting of a single puromycin aminonucleoside (PAN injection (intraperitoneally 15 mg/100 g body weight, with sacrifice after eight days. TAU limited proteinuria and podocytes foot processes effacement, and balanced slit diaphragm nephrin and glomerular claudin 1 expressions. In cortical proximal tubules, TAU improved lysosomal density, ER perimeter, restored proper ER-mitochondria tethering and mitochondrial cristae, and decreased inflammation. Remarkably, TAU downregulated glomerular ER stress markers (GRP78, GRP94, pro-apoptotic C/EBP homologous protein, activated caspase 3, tubular caspase1, and mitochondrial chaperone GRP75, but maintained anti-apoptotic HSP25. In conclusion, TAU, by targeting upstream ER stress separate from mitochondria dysfunctions at crucial renal sites, might be a promising dietary supplement in the treatment of the drug-resistant nephrotic syndrome.

  6. 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

  7. High Intensity Interval Training (HIIT) Induces Specific Changes in Respiration and Electron Leakage in the Mitochondria of Different Rat Skeletal Muscles.

    Science.gov (United States)

    Ramos-Filho, Dionizio; Chicaybam, Gustavo; de-Souza-Ferreira, Eduardo; Guerra Martinez, Camila; Kurtenbach, Eleonora; Casimiro-Lopes, Gustavo; Galina, Antonio

    2015-01-01

    High intensity interval training (HIIT) is characterized by vigorous exercise with short rest intervals. Hydrogen peroxide (H2O2) plays a key role in muscle adaptation. This study aimed to evaluate whether HIIT promotes similar H2O2 formation via O2 consumption (electron leakage) in three skeletal muscles with different twitch characteristics. Rats were assigned to two groups: sedentary (n=10) and HIIT (n=10, swimming training). We collected the tibialis anterior (TA-fast), gastrocnemius (GAST-fast/slow) and soleus (SOL-slow) muscles. The fibers were analyzed for mitochondrial respiration, H2O2 production and citrate synthase (CS) activity. A multi-substrate (glycerol phosphate (G3P), pyruvate, malate, glutamate and succinate) approach was used to analyze the mitochondria in permeabilized fibers. Compared to the control group, oxygen flow coupled to ATP synthesis, complex I and complex II was higher in the TA of the HIIT group by 1.5-, 3.0- and 2.7-fold, respectively. In contrast, oxygen consumed by mitochondrial glycerol phosphate dehydrogenase (mGPdH) was 30% lower. Surprisingly, the oxygen flow coupled to ATP synthesis was 42% lower after HIIT in the SOL. Moreover, oxygen flow coupled to ATP synthesis and complex II was higher by 1.4- and 2.7-fold in the GAST of the HIIT group. After HIIT, CS activity increased 1.3-fold in the TA, and H2O2 production was 1.3-fold higher in the TA at sites containing mGPdH. No significant differences in H2O2 production were detected in the SOL. Surprisingly, HIIT increased H2O2 production in the GAST via complex II, phosphorylation, oligomycin and antimycin by 1.6-, 1.8-, 2.2-, and 2.2-fold, respectively. Electron leakage was 3.3-fold higher in the TA with G3P and 1.8-fold higher in the GAST with multiple substrates. Unexpectedly, the HIIT protocol induced different respiration and electron leakage responses in different types of muscle.

  8. High Intensity Interval Training (HIIT Induces Specific Changes in Respiration and Electron Leakage in the Mitochondria of Different Rat Skeletal Muscles.

    Directory of Open Access Journals (Sweden)

    Dionizio Ramos-Filho

    Full Text Available High intensity interval training (HIIT is characterized by vigorous exercise with short rest intervals. Hydrogen peroxide (H2O2 plays a key role in muscle adaptation. This study aimed to evaluate whether HIIT promotes similar H2O2 formation via O2 consumption (electron leakage in three skeletal muscles with different twitch characteristics. Rats were assigned to two groups: sedentary (n=10 and HIIT (n=10, swimming training. We collected the tibialis anterior (TA-fast, gastrocnemius (GAST-fast/slow and soleus (SOL-slow muscles. The fibers were analyzed for mitochondrial respiration, H2O2 production and citrate synthase (CS activity. A multi-substrate (glycerol phosphate (G3P, pyruvate, malate, glutamate and succinate approach was used to analyze the mitochondria in permeabilized fibers. Compared to the control group, oxygen flow coupled to ATP synthesis, complex I and complex II was higher in the TA of the HIIT group by 1.5-, 3.0- and 2.7-fold, respectively. In contrast, oxygen consumed by mitochondrial glycerol phosphate dehydrogenase (mGPdH was 30% lower. Surprisingly, the oxygen flow coupled to ATP synthesis was 42% lower after HIIT in the SOL. Moreover, oxygen flow coupled to ATP synthesis and complex II was higher by 1.4- and 2.7-fold in the GAST of the HIIT group. After HIIT, CS activity increased 1.3-fold in the TA, and H2O2 production was 1.3-fold higher in the TA at sites containing mGPdH. No significant differences in H2O2 production were detected in the SOL. Surprisingly, HIIT increased H2O2 production in the GAST via complex II, phosphorylation, oligomycin and antimycin by 1.6-, 1.8-, 2.2-, and 2.2-fold, respectively. Electron leakage was 3.3-fold higher in the TA with G3P and 1.8-fold higher in the GAST with multiple substrates. Unexpectedly, the HIIT protocol induced different respiration and electron leakage responses in different types of muscle.

  9. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Han, B.; Zhao, Z.G.; Zhang, L.M.; Li, S.G.; Niu, C.Y. [Institute of Microcirculation, Hebei North University, Hebei Zhangjiakou (China)

    2015-04-28

    Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H{sub 2}S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H{sub 2}S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H{sub 2}S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H{sub 2}S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H{sub 2}S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H{sub 2}S and H{sub 2}S-mediated inflammation.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  11. The effects of prolonged CO2 insufflation on kidney function in a rat pneumoperitoneum model.

    Science.gov (United States)

    Yildirim, Dogan; Donmez, Turgut; Sunamak, Oguzhan; Mirapoglu, Semih; Hut, Adnan; Erdogan, Nilgun Rukiye; Saglam, Zumrut Mine Isık; Kilincaslan, Huseyin

    2017-06-01

    Pneumoperitoneum (PP) is known to cause ischemia in kidneys and other intra-abdominal organs because of decreased splanchnic blood flow. We aimed to determine the degree of renal injury that occurs due to a PP and prolonged PP. We measured renal injury biomarkers and made a histopathological evaluation to estimate the degree of injury and assessed the correlation of biomarkers with histopathological findings. Twenty-one female Sprague Dawley rats were separated randomly into three groups. Group 1 was the control group and was given anesthesia for 3 h. In group 2, a PP was administered under anesthesia for 1 h. A pneumoperitoneum was administered under anesthesia to animals in group 3 for 3 h. Pathological analysis showed a significant statistical difference between the 3 groups. In particular, neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys C) levels at the 24 th h and preoperative mean urea levels showed a significant difference between the groups. The 24 th -hour NGAL level in group 3 was significantly higher than that of group 1. The preoperative Cys C level was higher in group 1 than in either group 2 or 3. Cys C was decreased significantly in group 1 and increased significantly in both groups 2 and 3. The increase in NGAL and Cys C levels directly correlated with the duration of PP and intra-abdominal pressure, and they are therefore good biomarkers in diagnosing acute renal injury in the early phase. Serum creatinine level is not a good biomarker in the early phase of renal injury.

  12. Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model.

    Science.gov (United States)

    La Manna, Gaetano; Bianchi, Francesca; Cappuccilli, Maria; Cenacchi, Giovanna; Tarantino, Lucia; Pasquinelli, Gianandrea; Valente, Sabrina; Della Bella, Elena; Cantoni, Silvia; Claudia, Cavallini; Neri, Flavia; Tsivian, Matvey; Nardo, Bruno; Ventura, Carlo; Stefoni, Sergio

    2011-01-01

    Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

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

    Science.gov (United States)

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

    2008-01-01

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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun Oularbi

    2014-04-01

    Full Text Available Lambda-cyhalothrin (LCT is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administered orally over 28 days. The effects of the insecticide on various biochemical parameters were evaluated at 14 and 28 days. Histopathological studies were carried out in the kidneys and adrenal glands at the end of the experiment. Lambda-cyhalothrin, as a pyrethroid insecticide, induced significant increases (P≤0.05 in plasma urea, creatinine, uric acid and glucose concentrations, and alanine aminotransferase and aspartate aminotransferase activities after 14 and 28 days. In the rat plasma samples after 28 days, residual concentrations of LCT 1R, cis,

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

    Science.gov (United States)

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

    2018-05-01

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

  17. Monitoring hemodynamics and oxygenation of the kidney in rats by a combined near-infrared spectroscopy and invasive probe approach

    Science.gov (United States)

    Grosenick, Dirk; Cantow, Kathleen; Arakelyan, Karen; Wabnitz, Heidrun; Flemming, Bert; Skalweit, Angela; Ladwig, Mechthild; Macdonald, Rainer; Niendorf, Thoralf; Seeliger, Erdmann

    2015-07-01

    We have developed a hybrid approach to investigate the dynamics of perfusion and oxygenation in the kidney of rats under pathophysiologically relevant conditions. Our approach combines near-infrared spectroscopy to quantify hemoglobin concentration and oxygen saturation in the renal cortex, and an invasive probe method for measuring total renal blood flow by an ultrasonic probe, perfusion by laser-Doppler fluxmetry, and tissue oxygen tension via fluorescence quenching. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The hybrid approach was applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas. The approach was also applied to study the effects of the x-ray contrast medium iodixanol on the kidney.

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

    DEFF Research Database (Denmark)

    Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

    2017-12-11

    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

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

    Directory of Open Access Journals (Sweden)

    A. Caires

    2017-12-01

    Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

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

    Directory of Open Access Journals (Sweden)

    Andi N.K. Syarifin

    2015-11-01

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

  3. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. II. histoenzymatic studies

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, M.M.; Moniuszko-Jakoniuk, J. [Dept. of Toxicology, Medical Univ. of Bialystok, Bialystok (Poland); Kaminski, M.; Dziki, M. [Dept. of Histology and Embryology, Silesian School of Medicine, Katowice-Ligota (Poland)

    2004-04-01

    Early effects of cadmium (Cd) on the structure and function of the kidney were studied in an experimental model using rats intoxicated with Cd at the levels of 5 and 50 mg Cd/1 drinking water. The effect of Cd was evaluated histopathologically and biochemically. Damage to the cellular structures was assessed on the basis of histoenzymatic analyses of the activity and localization of indicator enzymes (succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphatase, Mg{sup 2+}-dependent adenosine triphosphatase and acid phosphatase). The histochemical observations indicate that Cd causes damage to the organization and function of the nephron. Several structures, i.e. endoplasmic reticulum, mitochondrion, lysosome, cellular and intracellular membrane, as well as their biological functions, i.e. aerobic and anaerobic respiration, transport functions and biochemical processes taking place in the endoplasmic reticulum, were affected. The cytotoxic action of Cd occurs mainly in the tubules and partially also in the glomeruli. The results clearly indicate that Cd damages kidney structurally and functionally even at a relatively low level (5 mg/l) corresponding to human environmental exposure, and they confirm our previous hypothesis that the threshold for the kidney effects of Cd is less than 4.08 {+-} 0.33 {mu}g/g kidney wet weight and higher than 2.40 {+-} 0.15 {mu}g/g. The target for Cd action in the kidney is the tubules (proximal convoluted tubules and straight tubules), and disturbance in their function is the main toxic effect of Cd. Renal glomeruli are also injured, but only partially, whereas in other parts of the nephron the damage is slight. The results, together with observations reported in the first paper of the study, incline us to conclude that humans environmentally exposed to Cd are at risk of tubular damage. (orig.)

  4. Effect of Antiretroviral Drug (arved) on the Kidney in Albino Rat ...

    African Journals Online (AJOL)

    African studies on effect of antiretroviral drugs on the kidney are limited resulting to scanty information on the safety of these drugs. This study was therefore designed to evaluate the effects of antiretroviral drugs arved®, on creatinine, urea, potassium and sodium ions as well as histological effect on the kidney. A total of fifty ...

  5. 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...

  6. Mitochondria in neutrophil apoptosis

    NARCIS (Netherlands)

    van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

    2006-01-01

    Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

  7. Kidney transplant

    Science.gov (United States)

    ... always take your medicine as directed. Alternative Names Renal transplant; Transplant - kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney - blood and urine flow Kidneys Kidney transplant - ...

  8. The effect of anthralin (dithranol) on mitochondria.

    Science.gov (United States)

    Morlière, P; Dubertret, L; Sa e Melo, T; Salet, C; Fosse, M; Santus, R

    1985-05-01

    The short-term effect of topical application of anthralin (dithranol) on normal human skin was investigated by electron microscopy. Mitochondria appeared markedly damaged. By contrast other cellular structures, particularly the nuclear and cytoplasmic membranes were unchanged. In vitro experiments were therefore performed on isolated rat liver mitochondria and it was shown that anthralin acts as an uncoupler of oxidative phosphorylation. These results suggest that anthralin can inhibit the adenosine triphosphate supply in epidermal cells. This loss of energy supply in keratinocytes could explain, at least in part, the therapeutic efficiency of anthralin in psoriasis.

  9. 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

  10. 6-Gingerol-Rich Fraction from Zingiber officinale Prevents Hematotoxicity and Oxidative Damage in Kidney and Liver of Rats Exposed to Carbendazim.

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-12-05

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

  12. Permanent catheterization of the carotid artery induces kidney infection and inflammation in the rat

    DEFF Research Database (Denmark)

    Fonseca, Uno Nicolas Kjærup; Nielsen, Sanne Gram; Hau, Jann

    2010-01-01

    Catheterization of the carotid artery and the jugular vein is one of the most commonly applied techniques used to gain intravascular access in pharmacology studies on rodents. We catheterized 10 rats by conventional clean techniques, 10 rats by aseptic techniques and 10 rats by conventional clean...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadzadeh-Vardin

    2015-06-01

    Full Text Available Purpose: Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI. However, the early death of transplanted mesenchymal stem cells (MSCs in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2, in MSCs could protect rats against AKI. Methods: The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI. Results: The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI. Conclusion: These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression.

  15. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  16. Protective effects of nettle (Urtica dioica extract against acute kidney injury induced by gentamycin in the rat

    Directory of Open Access Journals (Sweden)

    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

  17. 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

  18. The antiestrogen endoxifen protects rat liver mitochondria from permeability transition pore opening and oxidative stress at concentrations that do not affect the phosphorylation efficiency

    International Nuclear Information System (INIS)

    Ribeiro, Mariana P.C.; Silva, Filomena S.G.; Santos, Armanda E.; Santos, Maria S.; Custódio, José B.A.

    2013-01-01

    Endoxifen (EDX) is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptors that also inhibits aromatase activity. It is safe and well tolerated by healthy humans, but its use requires toxicological characterization. In this study, the effects of EDX on mitochondria, the primary targets for xenobiotic-induced toxicity, were monitored to clarify its potential side effects. EDX up to 30 nmol/mg protein did not affect the mitochondrial oxidative phosphorylation. At 50 nmol EDX/mg protein, EDX decreased the ADP phosphorylation rate and a partial collapse of mitochondrial membrane potential (Δψ), that parallels a state 4 stimulation, was observed. As the stimulation of state 4 was not inhibited by oligomycin and 50 nmol EDX/mg protein caused a slight decrease in the light scattering of mitochondria, these data suggest that EDX promotes membrane permeabilization to protons, whereas TAM at the same concentration induced mitochondrial membrane disruption. Moreover, EDX at 10 nmol/mg protein prevented and reversed the Ca 2+ -induced depolarization of ΔΨ and the release of mitochondrial Ca 2+ , similarly to cyclosporine A, indicating that EDX did not affect Ca 2+ uptake, but directly interfered with the proteins of the mitochondrial permeability transition (MPT) megacomplex, inhibiting MPT induction. At this concentration, EDX exhibited antioxidant activity that may account for the protective effect against MPT pore opening. In conclusion, EDX within the range of concentrations reached in tissues did not significantly damage the bioenergetic functions of mitochondria, contrarily to the prodrug TAM, and prevented the MPT pore opening and the oxidative stress in mitochondria, supporting that EDX may be a less toxic drug for women with breast carcinoma. - Highlights: ► Mitochondria are important targets of Endoxifen. ► Endoxifen prevents mitochondrial permeability transition. ► Endoxifen prevents oxidative stress in

  19. The antiestrogen endoxifen protects rat liver mitochondria from permeability transition pore opening and oxidative stress at concentrations that do not affect the phosphorylation efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Mariana P.C.; Silva, Filomena S.G.; Santos, Armanda E. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal); Santos, Maria S. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3004-517 Coimbra (Portugal); Custódio, José B.A., E-mail: custodio@ci.uc.pt [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal)

    2013-02-15

    Endoxifen (EDX) is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptors that also inhibits aromatase activity. It is safe and well tolerated by healthy humans, but its use requires toxicological characterization. In this study, the effects of EDX on mitochondria, the primary targets for xenobiotic-induced toxicity, were monitored to clarify its potential side effects. EDX up to 30 nmol/mg protein did not affect the mitochondrial oxidative phosphorylation. At 50 nmol EDX/mg protein, EDX decreased the ADP phosphorylation rate and a partial collapse of mitochondrial membrane potential (Δψ), that parallels a state 4 stimulation, was observed. As the stimulation of state 4 was not inhibited by oligomycin and 50 nmol EDX/mg protein caused a slight decrease in the light scattering of mitochondria, these data suggest that EDX promotes membrane permeabilization to protons, whereas TAM at the same concentration induced mitochondrial membrane disruption. Moreover, EDX at 10 nmol/mg protein prevented and reversed the Ca{sup 2+}-induced depolarization of ΔΨ and the release of mitochondrial Ca{sup 2+}, similarly to cyclosporine A, indicating that EDX did not affect Ca{sup 2+} uptake, but directly interfered with the proteins of the mitochondrial permeability transition (MPT) megacomplex, inhibiting MPT induction. At this concentration, EDX exhibited antioxidant activity that may account for the protective effect against MPT pore opening. In conclusion, EDX within the range of concentrations reached in tissues did not significantly damage the bioenergetic functions of mitochondria, contrarily to the prodrug TAM, and prevented the MPT pore opening and the oxidative stress in mitochondria, supporting that EDX may be a less toxic drug for women with breast carcinoma. - Highlights: ► Mitochondria are important targets of Endoxifen. ► Endoxifen prevents mitochondrial permeability transition. ► Endoxifen prevents oxidative

  20. 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.

  1. EVALUATION OF SOME ANTIOXIDANTS TREATMENT ON KIDNEY FUNCTION AND LIPID PEROXIDATION STATUS IN HYPERTENSIVE RATS INDUCED WITH L-NAME

    International Nuclear Information System (INIS)

    MATTA, T.F.

    2008-01-01

    Hypertension, the disease known as the s ilent killer , is a common problem facing peoples today with million new cases being diagnosed each year. Although a great amount of money is spent annually for the treatment and detection of this disease and its complications, current conventional treatment have done little to reduce the number of patients with hypertension. Research has found a variety of alternative therapies to be successful in reducing high blood pressure including diet, exercise, stress management, supplements and herbs.In this study, the changes in some selected biochemical blood variables, which are thought to represent risk factors coincident with hypertension and kidney function, were compared between a group of normotensive male albino rats and other group suffered from hypertension induced artificially by N-nitro-L-arginine methyl ester (L-NAME). Also, this study investigated the effects of daily administration of some antioxidants nutrients for two weeks namely carnitine, coenzyme Q 1 0 , garlic oil and their mixture on the same variables in order to show to what extent these nutrients are valid to control the levels of these variables without any deleterious effects after treatment. Fifty mg of coenzyme Q 10 and 50 mg of carnitine were daily injected intraperitoneally for two weeks in two groups of hypertensive rats while 200 mg/kg b.wt was given to another group of hypertensive rats by oral intubation. A combination of all the above mentioned nutrients was given to the fourth group. Another hypertensive group was left without any treatment and served as a recovery group. Fasting blood samples were drawn and kidney tissues were taken at the terminal of treatments.The obtained results revealed that induced hypertension caused significant (P<0.05) increase of thiobarbeturic acid reactive substances (TBARs), malondialdehyde (MAD), parathormone (PTH), renin, blood urea, creatinine, phosphorus, sodium and potassium while glutathione (GSH), calcium

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

    Science.gov (United States)

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

    2017-10-01

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

  3. The Preventive Role of Pioglitazone in Glycerol-Induced Acute Kidney Injury in Rats during Two Different Treatment Periods

    Directory of Open Access Journals (Sweden)

    Rama Mousleh

    2018-03-01

    Full Text Available Background: Acute kidney injury is the most life-threatening complication of rhabdomyolysis. Glycerol is commonly used to induce this injury. The aim was to investigate the renoprotective effects of pioglitazone and the possible advantage of administering the drug for a longer period. Methods: Twenty-four male Albino Wistar rats were randomly divided into 4 groups (n=6/group: (A control, (B glycerol (50%, 10 mL/kg intramuscularly, (C glycerol+pioglitazone (10 mg/kg orally for 3 days, and (D glycerol+pioglitazone (for 6 days. Serum urea and creatinine levels were measured to assess the renal function. Reduced glutathione (GSH levels and histological alterations were also measured. Statistical analysis was performed using Prism (version 6. The numerical data were evaluated by ANOVA, followed by the Tukey tests. The categorical data were evaluated by the Mann–Whitney test and the Fisher exact tests. P<0.05 was considered significant. Results: In the glycerol-injected rats, the serum urea and creatinine levels were increased (P<0.001, while the GSH levels were decreased (P<0.001 compared to Group A. The nephrotoxicity showed significant tubular (P=0.01 and glomerular (P=0.02 injuries. In the pioglitazone-treated rats, the changes in the serum biomarkers and in the GSH levels were reversed in Group C (P=0.01 and in Group D (P=0.01. The microscopic examinations of the kidneys also showed some improvement. No obvious statistically significant difference was found between these 2 preventive groups in most studied features. Conclusion: These results indicate that pioglitazone might have nephroprotective effects in this injury model. Pioglitazone succeeded in producing this effect within 3 days. Doubling the drug administration period did not produce any significant superior benefit.

  4. Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips

    International Nuclear Information System (INIS)

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Lotz, Kerstin; Ahr, Hans-J.; Dietrich, Daniel R.

    2006-01-01

    Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treated for 7 days and 6 months with 10 and 1 mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H and E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230 2 .0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats

  5. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

    International Nuclear Information System (INIS)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de; Vermeij, Marcel

    2007-01-01

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Male Lewis rats were injected with 278 or 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99m Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of 99m Tc-DMSA SPECT scintigrams at 130 days after [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

  6. Effect of Low Level Laser Irradiation at Wavelengths 488 and 515 nm on Glutamate Neurotransmitter in Mitochondria of Visual Brain Cortex in Albino Rat

    International Nuclear Information System (INIS)

    Omran, M.F.; El-Ahdal, M.A.; El-Kady, M.H.; Yousri, R.M.

    2004-01-01

    The presence of glutamate in the visual cortex and mitochondria could be used as a measure for the argon laser effect having wavelengths 488 and 515 nm, on the mitochondria. A comparative response for the bound and free glutamate was found. Irradiation with different energies 0.2, 0.5 and 1.0 J for both wavelengths were accomplished. This study makes us to recommend the advantage of using argon laser having wavelength 515 nm to enhance the blocking of glutamate and hence the reduction of brain toxicity. Most of the energy required for cellular functions comes from mitochondria (Shepherd, 1994). Glutamate, which is present in central nervous system at very high level is essential for brain intermediary metabolism (Frazer et al., 1994; Meldrum et al., 2000 and Blumcke et al., 2000). Glutamate is enriched in synaptic vesicles, the subcellular organelles, which are associated with the storage and release of neurotransmitters. Also, biochemical evidence for glutamate as neurotransmitter in fibers from the visual cortex to the subcortical visual relay nuclei has been indicated (Fose and Fonnum, 1987 and George, 1998)

  7. 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

  8. 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

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

    International Nuclear Information System (INIS)

    Slovinska, L.; Kropacova, K.; Kolesarova, M.; Misurova, E.

    2001-01-01

    The influence of Cd (1 mg/rat CdCl 2 i.p.) and/or gamma radiation (6 Gy) on RNA and DNA content and/or concentration in the intact kidney and hypertrophic kidney (on the 44th hour after unilateral nephrectomy - UN) and in other slowly and quickly proliferating organs was studied. The period between administration of Cd and ionizing irradiation (Ir) in the group with combined treatment was 30 min, between treatment (administration of Cd, Ir and combination of both treatments - Cd + Ir) and UN it was 1, 7, 14 and 21 days. The total extent of damage caused by the treatments in the investigated organs was following: intact kidney < liver < hypertrophic kidney and bone marrow < spleen < thymus. In the intact and hypertrophic kidney and liver, the administration of Cd caused more extensive changes in comparison with gamma irradiation and the effects of combination of the treatments were similar to those of Cd alone. In the bone marrow, spleen and thymus, more profound changes were observed after Ir in comparison with Cd administration, and the effects of combined treatment were similar to the effects of Ir alone. The changes in the hypertrophic kidney after administration of Cd and/or Ir were more extensive than in the intact kidney, which suggests latent injury induction in the rat kidney by these noxa. The higher effectiveness of the treatments in the hypertrophic kidney than in the intact one was manifested mostly by the decrease in the RNA and DNA content, which was mainly due to inhibition of growth induced by UN and not by a real decrease in DNA and RNA contents caused by loss of damaged cells. (author)

  10. Calcium isotope signature: new proxy for net change in bone volume for chronic kidney disease and diabetic rats.

    Science.gov (United States)

    Tanaka, Yu-Ki; Yajima, Nobuyuki; Higuchi, Yusuke; Yamato, Hideyuki; Hirata, Takafumi

    2017-12-01

    Herein, we measure the Ca isotope ratios ( 44 Ca/ 42 Ca and 43 Ca/ 42 Ca) in serum and bone samples collected from rats with chronic kidney disease (CKD) or diabetes mellitus (DM). For the serum samples, the isotope ratios are lower for the CKD (δ 44 Ca/ 42 Ca serum = 0.16 ± 0.11‰; 2SD, n = 6) and the DM (δ 44 Ca/ 42 Ca serum = -0.11 ± 0.25‰; 2SD, n = 7) rats than that for the control rats (δ 44 Ca/ 42 Ca serum = 0.25 ± 0.04‰; 2SD, n = 7). Bone samples from two distinct positions of 20 rats in total, namely, the center and proximal parts of the tibial diaphysis, are subject to Ca isotope analysis. The resulting δ 44 Ca/ 42 Ca values for the bone of the proximal part are about 0.3‰ lower than that for the serum samples from the same rats. The larger isotope fractionations between the serum and bone are consistent with previously reported data for vertebrate animals (e.g., Skulan and DePaolo, 1999), which suggests the preferential incorporation of lighter Ca isotopes through bone formation. For the bones from the control and CKD rats, there were no differences in the δ 44 Ca/ 42 Ca values between the positions of the bone. In contrast, the δ 44 Ca/ 42 Ca values of the bone for the DM rats were different between the positions of the bone. Due to the lower bone turnover rate for the DM rats, the δ 44 Ca/ 42 Ca for the middle of the diaphysis can reflect the Ca isotopes in the bone formed prior to the progression of DM states. Thus, the resulting δ 44 Ca/ 42 Ca values show a clear correlation with bone mineral density (BMD). This can be due to the release of isotopically lighter Ca from the bone to the serum. In the present study, our data demonstrate that the δ 44 Ca/ 42 Ca value for serum can be used as a new biomarker for evaluating changes in bone turnover rate, followed by changes in bone volume.

  11. Mitochondria in Lung Diseases

    Science.gov (United States)

    Aravamudan, Bharathi; Thompson, Michael A.; Pabelick, Christina M.; Prakash, Y. S.

    2014-01-01

    Summary Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabolism, energy production, calcium buffering, and cell fate determination. Regulation of their morphology and diverse activities beyond energy production are being recognized as playing major roles in cellular health and dysfunction. This review is aimed at summarizing what is known regarding mitochondrial contributions to pathogenesis of lung diseases. Emphasis is given to understanding the importance of structural and functional aspects of mitochondria in both normal cellular function (based on knowledge from other cell types) and in development and modulation of lung diseases such as asthma, COPD, cystic fibrosis and cancer. Emerging techniques that allow examination of mitochondria, and potential strategies to target mitochondria in the treatment of lung diseases are also discussed. PMID:23978003

  12. Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

    Directory of Open Access Journals (Sweden)

    Noeman Saad A

    2011-08-01

    Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

  13. Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

    NARCIS (Netherlands)

    Hendriksen, P.J.M.; Freidig, A.P.; Jonker, D.; Thissen, U.; Bogaards, J.J.P.; Mumtaz, M.M.; Groten, J.P.; Stierum, R.H.

    2007-01-01

    The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were

  14. 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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Hoon-In Choi

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  18. Effects of Vitamin C on Kidney and Bone of Rats Exposed to Low ...

    African Journals Online (AJOL)

    ABSTRACT: In this study, the effect of vitamin C on cadmium-induced toxicity was investigated. Wister rats were exposed to ... and muscles of cadmium exposed rats (1.0- ..... Fauci, A.S., Braunwald, K., Isselbacher, K.J., Wilson,. J.D., Martin ...

  19. Effects of dietary salt on adrenomedullin and its receptor mRNAs in rat kidney

    DEFF Research Database (Denmark)

    Jensen, B L; Gambaryan, S; Schmaus, E

    1998-01-01

    There is accumulating evidence that adrenomedullin (ADM) is involved in the control of salt and water homeostasis. ADM is considered to act primarily in a paracrine fashion, and since the kidneys are target organs for ADM, we investigated the localization and regulation of ADM and ADM receptor (ADM...... and a preferential action of ADM in the papilla. Ten days of feeding a low-salt (0.02%) or a high-salt diet (4%) did not change ADM mRNA or ADM-R mRNA in any kidney zone....

  20. 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

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

    Science.gov (United States)

    Ncir, Marwa; Saoudi, Mongi; Sellami, Hanen; Rahmouni, Fatma; Lahyani, Amina; Makni Ayadi, Fatma; El Feki, Abdelfattah; Allagui, Mohamed Salah

    2017-09-18

    The present study investigated the in vitro and the in vivo antioxidant capacities of Allium sativum (garlic) extract against deltamethrin-induced oxidative damage in rat's brain and kidney. The in vitro result showed that highest extraction yield was achieved with methanol (20.08%). Among the tested extracts, the methanol extract exhibited the highest total phenolic, flavonoids contents and antioxidant activity. The in vivo results showed that deltamethrin treatment caused an increase of the acetylcholinesterase level (AChE) in brain and plasma, the brain and kidney conjugated dienes and lipid peroxidation (LPO) levels as compared to control group. The antioxidant enzymes results showed that deltamethrin treatment induced a significantly decrease (p < 0.01) in brain and kidney antioxidant enzymes as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) to control group. The co-administration of garlic extract reduced the toxic effects in brain and kidney tissues induced by deltamethrin.

  2. Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Wickes, W A; Wiskich, J T

    1976-01-01

    The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

  3. A survey of the interaction of calcium ions with mitochondria from different tissues and species

    Science.gov (United States)

    Carafoli, Ernesto; Lehninger, Albert L.

    1971-01-01

    A survey was made of the capacity of mitochondria isolated from a number of different tissues and species to accumulate Ca2+ from the suspending medium during electron transport. The species examined included the rat, mouse, rabbit, hamster, guinea pig, cow, chicken, turtle, blowfly, yeast and Neurospora crassa. The tissues examined included vertebrate liver, kidney, brain, heart, spleen, thyroid and adrenal cortex, and the flight muscle of the blowfly. The mitochondria from all vertebrate tissues examined showed: (a) stimulation of State 4 respiration by added Ca2+ (Ca2+/~ activation ratio about 2.0), accompanied by accumulation of Ca2+ and ejection of H+, with a H+/Ca2+ ratio about 1.0; (b) a requirement of phosphate for accumulation of large amounts of Ca2+; (c) respiration-independent high-affinity binding sites for Ca2+; (d) endogenous Ca2+, which is largely released by uncoupling agents. However, mitochondria from yeast and blowfly flight muscle are unable to accumulate Ca2+ in a respiration-dependent process and possess no high-affinity Ca2+-binding sites. These findings support the view that the high-affinity sites represent the ligand-binding sites of a specific Ca2+ `permease' or transport system in the membrane. The relatively high affinity for Ca2+, which equals or exceeds the affinity for ADP, and the generally uniform characteristics of Ca2+ transport in all the vertebrate mitochondria tested strongly suggest that respiration-linked Ca2+ accumulation plays a general and fundamental role in vertebrate cell physiology. PMID:5129264

  4. Alterations of NO synthase isoforms in brain and kidney of rats with genetic and salt hypertension

    Czech Academy of Sciences Publication Activity Database

    Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

    2010-01-01

    Roč. 59, č. 6 (2010), s. 997-1009 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/08/0139 Institutional research plan: CEZ:AV0Z50110509 Keywords : brainstem * diencephalon * kidney Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  5. Azilsartan Improves Glycemic Status and Reduces Kidney Damage in Zucker Diabetic Fatty Rats

    Czech Academy of Sciences Publication Activity Database

    Khan, M. A. H.; Neckář, Jan; Haines, J.; Imig, J. D.

    2014-01-01

    Roč. 27, č. 8 (2014), s. 1087-1095 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : azilsartan medoxomil * blood pressure * hypertension * inflammation * kidney injury * oxidative stress * type 2 diabetes Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.852, year: 2014

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

    Science.gov (United States)

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

  7. Orally Active Epoxyeicosatrienoic Acid Analog Attenuates Kidney Injury in Hypertensive Dahl Salt–Sensitive Rat

    Czech Academy of Sciences Publication Activity Database

    Khan, M. A. H.; Neckář, Jan; Manthati, V.; Errabelli, R.; Pavlov, T. S.; Staruschenko, A.; Falck, J. R.; Imig, J. D.

    2013-01-01

    Roč. 62, č. 5 (2013), s. 905-913 ISSN 0194-911X Institutional support: RVO:67985823 Keywords : kidney * hypertension * oxidative stress * inflammation * arachidonate epoxygenase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 7.632, year: 2013

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

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    Lee, Sang-Keel

    2000-12-01

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

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

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    H Aqababa

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Piliang Hao

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  14. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

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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.

  15. Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats.

    Science.gov (United States)

    Lakshmi, G Dhana; Kumar, P Ravi; Bharavi, K; Annapurna, P; Rajendar, B; Patel, Pankaj T; Kumar, C S V Satish; Rao, G S

    2012-02-01

    Administration of cadmium (Cd) significantly increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney tissues. Cadmium also caused a significant alteration in hepatic and renal functional markers in serum viz. total protein, albumin, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were severe vascular and sinusoidal congestion with diffuse degenerative changes and mononuclear infiltration into peripheral areas, while the kidney showed vascular and glomerular congestion, cloudy swelling of tubular epithelium. Coadministration of ethonolic extract of T. terrestris or vitamin E along with Cd significantly reversed the Cd induced changes along with significant reduction in Cd load.

  16. Effect of cisplatin on proximal convoluted and straight segments of the rat kidney

    DEFF Research Database (Denmark)

    Daugaard, G; Holstein-Rathlou, N H; Leyssac, P P

    1988-01-01

    lithium clearance (CLi/Cin) and e-TT/OT was observed (from 270 +/- 32 to 387 +/- 60 microliters/min/g kidney weight, 0.202 +/- 0.03 to 0.340 +/- 0.06 and 0.415 +/- 0.02 to 0.497 +/- 0.02, respectively). These increases indicate an increased fluid delivery from both the proximal straight segment...

  17. 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.

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

    Science.gov (United States)

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

    2017-01-10

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

  19. Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

    Science.gov (United States)

    Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

    2014-08-15

    Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

  20. Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves.

    Science.gov (United States)

    Adeyemi, O S; Akanji, M A

    2011-09-01

    Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.

  1. 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

  2. On Cellular Darwinism: Mitochondria.

    Science.gov (United States)

    Bull, Larry

    2016-01-01

    The significant role of mitochondria within cells is becoming increasingly clear. This letter uses the NKCS model of coupled fitness landscapes to explore aspects of organelle-nucleus coevolution. The phenomenon of mitochondrial diversity is allowed to emerge under a simple intracellular evolutionary process, including varying the relative rate of evolution by the organelle. It is shown how the conditions for the maintenance of more than one genetic variant of mitochondria are similar to those previously suggested as needed for the original symbiotic origins of the relationship using the NKCS model.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Wu S

    2014-12-01

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

  6. The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats.

    Science.gov (United States)

    Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh

    2018-01-01

    Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

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

    Science.gov (United States)

    Xu, Xing-xin; Qi, Xiang-Ming; Zhang, Wei; Zhang, Chao-Qun; Wu, Xiao-Xu; Wu, Yong-Gui; Wang, Kun; Shen, Ji-Jia

    2014-05-15

    TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Imad M Al-Ani

    2017-08-01

    Full Text Available Background: The aims of this study were to explore the antihyperglycemic effect of curry leaves, Murraya koenigii "MK" aqueous extract, and to examine its possible protective effects on the islets of Langerhans and kidneys of streptozotocin (STZ diabetic rats. Methods: Thirty healthy adult male Sprague Dawley rats were randomized into five groups (n=6; normal control, normal treated with "MK" control, diabetic control (non-treated with "MK", diabetic treated with 200 mg/kg MK aqueous leaf extract and diabetic treated with 400 mg/kg MK aqueous leaf extract. Blood glucose levels and body weight were monitored gravimetrically. The animals were sacrificed on the 30th day; the kidney and pancreatic tissues were processed for histological studies. Results: The diabetic group showed considerable loss of body weight and increase in blood glucose levels and degeneration of the glomeruli and renal convoluted tubules and atrophied islets with disintegration of β-cells. Treatment of diabetic rats with MK extract showed significant (p < 0.001 improvement in blood glucose levels and body weight gain. The MK extract also caused an improvement in tissue injury induced by STZ injection in the kidney and islets of Langerhans. Conclusions: These findings highlighted the beneficial effects of MK aqueous extract against cellular oxidative damage in STZ-induced diabetic rats.

  9. Fructus ligustri lucidi ethanol extract improves bone mineral density and properties through modulating calcium absorption-related gene expression in kidney and duodenum of growing rats.

    Science.gov (United States)

    Feng, Xin; Lyu, Ying; Wu, Zhenghao; Fang, Yuehui; Xu, Hao; Zhao, Pengling; Xu, Yajun; Feng, Haotian

    2014-04-01

    Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague-Da