Effects of alpha-tocopherol on carbon tetrachloride metabolism in rat liver microsomes.
alpha-tocopherol is the major lipid-soluble radical-scavenging antioxidant in rat liver. It has long been used as a putative protective agent in CCl4 induced liver injury but with variable results. We have used alpha-tocopherol loaded rat liver microsomes to study the effect of this vitamin on CCl4 metabolism in vitro. As expected, alpha-tocopherol inhibits CCl4-dependent microsomal lipid peroxidation and, at a very high concentration, will inhibit the covalent binding of CCl3 to microsomal protein by up to 50%. No inhibitory effect was observed towards CCl3 production as measured by the electron spin resonance technique of spin-trapping but this apparent discrepancy may represent a limitation of the technique. The high levels required to inhibit covalent binding probably preclude the likelihood of alpha-tocopherol significantly affecting that phenomenon at endogenous concentrations but may be relevant to other experiments employing high doses of alpha-tocopherol as an experimental hepatoprotective agent.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology*
D014810:Vitamin E; D002251:Carbon Tetrachloride; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase