EFFECTS OF VARIOUS COMPOUNDS ON LIPID PEROXIDATION MEDIATED BY DETERGENT-SOLUBILIZED RAT LIVER NADPH-CYTOCHROME C REDUCTASE

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A reconstituted lipid peroxidation system containing NADPH-cytochrome c reductase isolated from detergent-solubilized rat liver microsomes was used to determine the effects of several compounds, including drugs, on the lipid peroxidation activity. EDTA and ferrous ion were essential requirements for reconstitution of the activity. The addition of 1, 10-phenanthroline to the system containing both EDTA and ferrous ion further enhanced the activity. Pyrocatecol, thymol, p-aminophenol, imipramine, p-chloromercuribenzoate (PCMB) and α-tocopherol exhibited strong inhibition, aniline, N-monomethylaniline, aminopyrine, benzphetamine, SKF 525-A and NADP exhibited moderate inhibition, and phenol, benzoic acid, acetanilide and nicotinamide exhibited less or no inhibition at the concentrations lower than 1000 μM. Metal ions such as Hg⁺, Hg²⁺, Co²⁺, Cu²⁺, Mn²⁺ and U⁶⁺ inhibited lipid peroxidation strongly. In addition, Cd²⁺, St²⁺ and Ca²⁺ exhibited less potent to moderate inhibition, and Ba²⁺ and Mg²⁺ were without effects on the activity. Among sulfhydryl compounds tested, dithiothreitol inhibited lipid peroxidation to a greater extent than did the other three compounds, glutathione, cysteine and mercaptoethanol.