چكيده لاتين :
Addition of n-butyl nitrite to isolated rat hepatocytes caused an immediate
glutathione depletion followed by an inhibition of mitochondrial respiration,
inhibition 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 nitriteinduced
mitochondrial respiration inhibition, ATP depletion, lipid peroxidation
and plasma membrane disruption. However, glutathione depletion, S-nitrosoglutathione
(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 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.
