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Freundt KJ, Romer KG, Kamal AM: The inhibitory action of dithiocarbamates and carbon disulphide on malondialdehyde formation resulting from lipid peroxidation in rat liver microsomes. J Appl Toxicol. 1981 Aug;1(4):215-9.
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. |
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