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 anti oxidant enzyme status and the expression of fibrosis-related marker protein s in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal f ailure with development of tubulo-interstitial fibrosis and glomerulosclero sis. Lipids accumulate in blood and in both glomeruli and tubulo-interstiti al tissue. Desmin and alpha-smooth muscle actin expression increases in glo meruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for c atalase, to 56% for total superoxide dismutase and to 69% for glutathione p eroxidase). The mRNA levels of catalase, Cu/Zn-super oxide dismutase and gl utathione peroxidase-l evaluated by Northern blot are decreased by more tha n 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-l . We conclude that in the rat Adriamycin-induced model of chronic renal fai lure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissu e facilitates oxidative damage. Development of fibrosis is paralleled by in creased expression of desmin and a-smooth muscle actin. Copyright (C) 2000 S.Karger AG. Basel.