Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450.
Treatment of rats with ethanol or rabbits with either imidazole or pyrazole, agents known to induce the ethanol-inducible form of liver microsomal cytochrome P-450 (P-450 LMeb), caused, compared to controls, 3-25-fold enhanced rates of CCl4-dependent lipid peroxidation or chloroform production in isolated liver microsomes. No significant differences were seen when the rate of CCl4-dependent lipid peroxidation was expressed relative to the amount of P-450 LMeb in the various types of microsomal preparations. In reconstituted membranous systems, this type of P-450 was a 100-fold more effective catalyst of CCl4 metabolism than either of the cytochromes P-450 LM2 or P-450 LM4. It is proposed that the induction of this isozyme provides the explanation on a molecular level for the synergism seen of ethanol on CCl4-dependent hepatotoxicity.
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002725:Chloroform / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004357:Drug Synergism; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011817:Rabbits; D013997:Time Factors
D007527:Isoenzymes; D008054:Lipid Peroxides; D000431:Ethanol; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride