EFFECT OF LINOLEIC ACID HYDROPEROXIDEON LIVER MICROSOMAL ENZYMES IN VITRO

Abstract

Rat liver microsomes incubated with linoleic acid hydroperoxide (LAHPO) lost cytochrome P-450 specifically among the enzymes of microsomal electron transport systems. The loss of cytochrome P-450 content and glucose-6-phosphatase activity by LAHPO was accompanied by an increase in malondialdehyde (MDA) production. Microsomal suspension turbidity was decreased with increasing MDA production but not proportionately. Diethyldithiocarbamate (DTC), N,N''-diphenyl-p-phenylenediamine and .alpha.-tocopherol inhibited almost completely the LAHPO-induced MDA production of microsomes; no perfect protection against the loss of cytochrome P-450 content and glucose-6-phosphatase activity was seen. The decrease of microsomal turbidity by LAHPO was little affected in the presence of DTC. Purified cytochrome P-450 was destroyed by LAHPO with minimal protection by the compounds described above. The loss of microsomal enzyme activities during lipid peroxidation may be largely due to a direct attack on enzyme proteins by lipid peroxides rather than indirectly to a structural damage of microsomal membranes resulting from peroxidative breakdown of membrane lipids.