Paraquat-induced alterations of phospholipids and GSSG-release in the isolated perfused rat liver, and the effect of SOD-active copper complexes

Abstract

The possibility that generation of active oxygen species and lipid peroxidation are involved in paraquat toxicity was examined through the use of the Superoxide dismutase-active, low molecular weight copper complexes Cu(tyr) 2 and Cu-penicillamine. In addition, it was investigated whether the oxidation of glutathione is directly associated with paraquat-induced lipid peroxidation. An increase in diene absorption and a decrease in phospholipids of mitochondria and microsomes isolated after perfusion of rat livers with paraquat could be observed. These effects may be explained by lipid peroxidation. Cu(tyr) 2 abolished these effects of paraquat. In contrast, the increase of GSSG-release into the perfusate upon paraquat-treatment could not be influenced by Cu-penicillamine and was only partially inhibited by Cu(tyr) 2. Therefore the GSSG-release cannot be the result of paraquat-induced generation of O 2 − or lipid peroxidation and seems more likely to be caused by the NADPH depleting action of paraquat. It is proposed that the alterations suggesting lipid peroxidation may only be observed if hepatic glutathione content decreased below a critical value.