فهرست نشریات علمی دسترسی آزاد ایران

Addition of n-butyl nitrite to isolated rat hepatocytes caused an immediate glutathione depletion followed by an inhibition of mitochondrial respiration, inhibitionof glycolysis and ATP depletion. At cytotoxic butyl nitrite concentrations, lipid peroxidation occurred before the plasma membrane was disrupted.Cytochrome P-450 inhibitors inhibited peroxynitrite formation and prevented butyl nitrite-induced mitochondrial respiration inhibition, ATP depletion, lipidperoxidation and plasma membrane disruption. However, glutathione depletion, S-nitroso-glutathione (GSNO) formation, or the inhibition of glycolysis was notaffected by cytochrome P-450 inhibitors. Glutathione-depleted hepatocytes were resistant to butyl nitrite which suggests that cytotoxicity and peroxynitrite formation results from GSNO formation. Peroxynitrite formation was also inhibited by reactive oxygen scavengers. These findings suggest that cytochrome P-450 isoforms (particularly CYP2E1) act as a source of superoxide anion radicals in the formation of cytotoxic peroxynitrite from nitric oxide.