BIOCHEMICAL BASIS FOR IN VITRO PRO-OXIDANT ACTION OF CARBON TETRACHLORIDE

The occurrence of TPNH-linked liver microsomal lipid peroxidation has been confirmed in the present study. Cytochrome c and ferricyanide were effective inhibitors in vitro of malonaldehyde production in hepatic microsomes and microsome-supernatant fractions, but only when added at the beginning of the incubation. Although malonaldehyde formation ceased when EDTA was added to a microsome-supernatant preparation undergoing vigorous lipid peroxidation, cytochrome c or ferricyanide, when added at a similar time, did not affect the further course of lipid peroxidation. A pro-oxidant action of carbon tetrachloride which required TPNH as a cofactor was demonstrated in washed liver microsome preparations. Addition of carbon tetrachloride produced an increase in malonaldehyde formation in this system. When a TPNH-generating system was added to the microsome-supernatant fraction of rat liver, malonaldehyde production was depressed, and in this supplemented microsome-supernatant system carbon tetrachloride exhibited a marked pro-oxidant action. Addition of reduced glutathione to a microsome-supernatant system supplemented with a TPNH-generating system resulted in a further suppression of spontaneous lipid peroxidation, and in this system a maximal pro-oxidant effect of added carbon tetrachloride was observed. Benzene and heptane did not exhibit pro-oxidant actions in hepatic microsome-supernatant fractions supplemented with TPNH. The role of the microsomal electron transport system in the necrogenic action of carbon tetrachloride is briefly discussed. Alteratons of this system may explain why certain substances protect the liver from carbon tetrachloride-induced damage as well as why other materials potentiate the effects of the haloalkane. © 1969.