Changes in antioxidant defence systems induced by cyclosporine A in cultures of hepatocytes from 2- and 12-month-old rats.

摘要: Abstract The in vitro effect of cyclosporine A (CsA) was studied reference to the production reactive oxygen species (peroxides and superoxide anion) cell enzyme-mediated antioxidant defence hepatocytes isolated from rats aged 2 12 months. Primary cultures were incubated presence concentrations range 0 50 μM for 24 hr, release lactate dehydrogenase into culture medium evaluated as a parameter cytotoxicity membrane lysis. Peroxides quantified by using 2′,7′-dichlorodihydrofluorescein diacetate, anion levels fluorescence dihydroethidium. Enzyme activity gene expression catalase Mn- Cu,Zn-superoxide dismutase also assayed. CsA significantly higher months when compared those Intracellular peroxide content resulted dose-dependent increase, while intracellular level slightly decreased increased 0–50 μM. progressive increase peroxides associated with loss viability accompanied enzyme activities mRNAs, slight increases mRNA. We conclude that, primary hepatocyte cultures, both age groups 12-month-old 2-month-old animals. non-coordinated regulation systems, i.e. dismutases, evidenced greater extent older group rats, could be one mechanisms involved toxicity.