Inhibition of hepatic microsomal lipid peroxidation by drug substrates without drug metabolism.
Miles-PR; Wright-JR; Bowman-L; Colby-HD
Biochem Pharmacol 1980 Feb; 29(4):565-570
The relationship between drug metabolism and lipid peroxidation in rat hepatic microsomes was investigated. Addition of aniline (62533), beta-diethylaminoethyl-diphenylpropylacetate (62680) (SKF- 525A), aminopyrine (58151), benzo(a)pyrene (50328), or ethylmorphine (76584) to cultures of rat hepatic microsomes caused almost complete inhibition of nicotinamide-adenine-dinucleotide-phosphate (NADPH) or enzymatic induced lipid peroxidation. These substrates also inhibited ascorbate or nonenzymatic induced lipid peroxidation in microsomes in which drug metabolizing enzymes were inactivated by heat treatment. The substrate concentrations which produced half maximal inhibition were similar for both NADPH and ascorbate induced lipid peroxidation. The addition of metyrapone (54364) had no effect on either half maximal or maximal substrate inhibition of NADPH induced lipid peroxidation. All five substrates inhibited ferrous iron stimulated peroxidation of linoleic-acid. The authors conclude that inhibition of hepatic microsomal lipid peroxidation by drug substrates is not dependent on substrate metabolism. They suggest that the antioxidant properties of the substrates are responsible for the inhibition of hepatic lipid peroxidation.
NIOSH-Author; Liver-enzyme; Enzymatic-action; Oxidative-enzymes; Chemical-exposure; Enzymatic-inhibition; Lipids; Metabolic-effects
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