The inhibitory action of dithiocarbamates and carbon disulphide on malondialdehyde formation resulting from lipid peroxidation in rat liver microsomes.

Abstract

The dithiocarbamates (DTCs) disulfiram, thiram, diethyldithiocarbamate and dimethyldithiocarbamate on the equimolar base inhibited to the same extent both the lipid peroxidation (LPO) induced by ascorbic acid (non-enzymatic) and that stimulated by an NADPH-regenerating system with CCl4 admixture (enzymatic). Lipid peroxidation measurements were made in terms of malondialdehyde (MDA) formation in rat liver microsomes, or in the 9000 X g supernatant. The inhibitory action of tetramethylthiuram monosulphide was considerably weaker. Carbon disulphide (CS2) inhibited the enzymatic and non-enzymatic stimulated microsomal LPO by 4 orders less than the DTCs. In parallel with the inhibition of MDA formation, oxidative destruction of microsomal cytochrome P-450 was delayed with increasing concentrations of the DTCs. A well-correlated, non-linear, semi-logarithmic relation was found for the concentration-activity relationship for all DTCs and CS2. As the DTCs inhibited LPO both in heat-denatured and freshly prepared microsomes, it can be deduced that the DTCs intervene in a non-enzymatic oxidation phase of the LPO. The DTC inhibitory action is attributed to a radical-trap mechanism since LPO that has already been initiated was inhibited with the DTCs. However, more inhibitor is required to trap the radicals the later the DTC administration takes place.