STUDIES ON DESTRUCTION OF LIVER MICROSOMAL CYTOCHROME P-450 BY CARBON TETRACHLORIDE ADMINISTRATION

Carbon tetrachloride impairs the oxidative enzymes in liver microsomes by decreasing the amount of cytochrome P-450. The destruction is probably not mediated by an increase in lipid peroxidation, since ethanol which promotes lipid peroxidation does not decrease cytochrome P-450 or the metabolism of ethylmorphine. The decrease in cytochrome P-450 is not due to destruction of liver cells or to altered permeability of endoplasmic reticulum because NADPH cytochrome c reductase was not detected in plasma and was not decreased in liver microsomes. The solvent effect of CCl4 probably does not account for the decrease in cytochrome P-450 because CHCl3 and CH2Cl2 did not decrease the cytochrome. Our results are in accord with the view that CCl4 acts through an active metabolite, but they do not necessarily imply that the active metabolite is formed by a cytochrome P-450 enzyme. © 1968.