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      Vitamin E Protects Renal Antioxidant Enzymes and Attenuates Glomerulosclerosis in Adriamycin-Treated Rats


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          Background/Aims: In the rat Adriamycin model of chronic renal failure, the development of glomerulosclerosis and tubulointerstitial lesions is accompanied by decreased activities and mRNA levels of the antioxidant enzymes. In this study, we investigated the effect of oral vitamin E supplementation on antioxidant enzyme activities in both the cortex and isolated glomeruli from Adriamycin-treated rats. Methods: Glomerulosclerosis, tubulointerstitial lesions and ferric iron deposits were evaluated by histochemical staining methods, and antioxidant enzyme activities were measured by spectrophotometry. Results: Vitamin E supplementation of the normal diet attenuates Adriamycin-induced glomerulosclerosis and tubulointerstitial lesions, but not proteinuria and serum total cholesterol, low-density lipoprotein cholesterol, triglycerides and total protein concentrations. In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase, catalase and glutathione peroxidase, and partly for Mn superoxide dismutase. Conclusion: Dietary supplementation of vitamin E protects the activities of antioxidant enzymes in the kidney cortex and glomeruli, and attenuates the evolution towards terminal renal failure in rats treated with Adriamycin.

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          Role of free radicals in the pathogenesis of lipid-induced glomerulosclerosis in rats.

          We examined whether a high-cholesterol (HC) diet causes glomerulosclerosis in rats, and investigated the role of free radicals and lipid peroxidation in lipid-induced glomerulosclerosis.
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            Renal Antioxidant Enzymes and Fibrosis-Related Markers in the Rat Adriamycin Model

            Excessive generation of reactive oxygen intermediates can induce changes in the cellular antioxidant defence system. In this study we examine the antioxidant enzyme status and the expression of fibrosis-related marker proteins in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin and α-smooth muscle actin expression increases in glomeruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for catalase, to 56% for total superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin-induced model of chronic renal failure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissue facilitates oxidative damage. Development of fibrosis is paralleled by increased expression of desmin and α-smooth muscle actin.
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              Effect of Vitamin E on Adriamycin- Induced Nephrotoxicity at the Ultrastructural Level in Guinea Pigs

              It is known that Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. In this study, we have established that vitamin E has some beneficial effects on the kidney by protecting it from some of the toxcity induced by Adriamycin. A study was carried out which comprised one control group and two experimental groups of guinea pigs. In the experiment Adriamycin was administered either alone (group II) or together with vitamin E (group III). The results of groups II and III were compared with controls (group I). The kidneys were subsequently removed and examined by routine electron microscopic techniques. We found that vitamin E administered together with Adriamycin could reverse some of the degenerative changes caused by Adriamycin.

                Author and article information

                S. Karger AG
                May 2002
                02 May 2002
                : 91
                : 1
                : 129-133
                aDepartment of Human Anatomy, bLearning Resource Centre and cDepartment of Nephrology, Vrije Universiteit Brussel, Belgium
                57614 Nephron 2002;91:129–133
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 1, References: 23, Pages: 5
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/57614
                Self URI (text/html): https://www.karger.com/Article/FullText/57614
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                Ferric iron,Glomeruli,Oxidative stress,Superoxide dismutase,Catalase,Glutathione peroxidase


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