Lipid peroxidation as a consequence of glutathione depletion in rat and mouse liver

Treatment of rats and mice with either vinylidene chloride or diethylmaleate led to a time-dependent depletion of liver glutathione (GSH). Incubations of liver homogenates from such glutathione-depleted animals resulted in a large increase of the spontaneous lipid peroxidation. This was suppressed by the hepatoprotective agents (+)-cyanidanol-3 and dithiocarb which may both act as antioxidants and radical scavengers while dithiocarb, in addition, inhibits the microsomal monooxygenase system. Addition of glutathione in a physiological concentration range totally inhibited lipid peroxidation. These findings are interpreted in terms of glutathione depletion leading per se to an increased lipid peroxidation, possibly due to its lack as part of the cellular defence system against endogenous toxic intermediates.