involvement of cytochrome p-450 in n-butyl nitrite-induced hepatocyte cytotoxicity
نویسندگان
چکیده
addition of n-butyl nitrite to isolated rat hepatocytes caused an immediate glutathione depletion followed by an inhibition of mitochondrial respiration, inhi- bition of 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, lipid peroxidation and plasma membrane disruption. however, glutathione depletion, s-nitroso-glutathione (gsno) formation, or the inhibition of glycolysis was not affected by cytochrome p-450 inhibitors. glutathione-depleted hepatocytes were resistant to butyl nitrite which suggests that cytotoxicity and peroxynitrite forma- tion results from gsno formation. peroxynitrite formation was also inhibited by reactive oxygen scavengers. these findings suggest that cytochrome p-450 iso- forms (particularly cyp2e1) act as a source of superoxide anion radicals in the formation of cytotoxic peroxynitrite from nitric oxide.
منابع مشابه
Involvement of Cytochrome P-450 in n-Butyl Nitrite-Induced Hepatocyte Cytotoxicity
Addition of n-butyl nitrite to isolated rat hepatocytes caused an immediate glutathione depletion followed by an inhibition of mitochondrial respiration, inhi- bition of 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 prev...
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عنوان ژورنال:
iranian journal of pharmaceutical sciencesجلد ۱، شماره ۱، صفحات ۱۱-۱۹
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