Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450

FEBS Lett. 1985 Apr 22;183(2):265-9. doi: 10.1016/0014-5793(85)80790-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / pharmacology*
  • Chloroform / metabolism
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Drug Synergism
  • Enzyme Induction
  • Ethanol / pharmacology*
  • Isoenzymes / biosynthesis*
  • Lipid Peroxides / metabolism*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Rabbits
  • Time Factors


  • Isoenzymes
  • Lipid Peroxides
  • Ethanol
  • Chloroform
  • Cytochrome P-450 Enzyme System
  • Carbon Tetrachloride