Initiation of in vitro lipid peroxidation by N-hydroxynorcocaine and norcocaine nitroxide

Norcocaine nitroxide and N-hydroxynorcocaine were found to stimulate hepatic microsomal lipid peroxidation in vitro, as measured by spin-trapping techniques using the spin trap alpha-[4-pyridyl-1-oxide]-N-tert-butylnitrone. It was determined that either norcocaine nitroxide or N-hydroxynorcocaine markedly enhanced the rate of spin trapping of lipid peroxyl radicals when added to hepatic microsomal preparations. Glutathione, in the presence of dialyzed cytosol, inhibited the formation of lipid peroxyl spin-trapped adducts. This finding suggests that cytosolic glutathione-dependent enzymes perhaps including glutathione peroxidase play an important role in the prevention of norcocaine nitroxide-or N-hydroxynorcocaine-mediated lipid peroxidation.