Effect of L-carnitine supplementation on xenobiotic-metabolizing hepatic enzymes exposed to methanol

Exp Toxicol Pathol. 2006 Jul;57(5-6):427-35. doi: 10.1016/j.etp.2006.03.001. Epub 2006 Apr 17.

Abstract

The study aimed to evaluate the effect of L-carnitine on hepatic cytochrome P450-dependent monooxygenases exposed to methanol. Male Spraque-Dawley rats were given methanol (1/4 LD50 and 1/2 LD50) together with L-carnitine (1g/kg body weight). The parameters of microsome electron transport chains I and II and the levels of CYP2E1, CYP2B1/2 and CYP1A2 were measured 8, 12, 24, 48, 72 and 96 h after exposure. L-carnitine did not affect cytochrome P450 but it significantly increased at 72 and 96 h NADPH-cytochrome P450 reductase. It stimulated cytochrome b5 at 48 and 96 h and NADH-cytochrome b5 reductase activity at 12, 72 and 96 h. Methanol, especially the lower dose, inhibited cytochrome P450 after 48 h, but the higher methanol dose inhibited NADH-cytochrome b5 reductase activity in this time. L-carnitine, combined with the lower dose of methanol, stimulated NADPH-cytochrome P450 reductase after 48 h and cytochrome b5 and NADH-cytochrome b5 reductase over the whole period of observation. L-carnitine stimulated CYP2B1/2 but not CYP2E1 and CYP1A2. Methanol stimulated CYP2E1 at 24 h, but CYP1A2 at 96 h in the studied doses. CYP2B1/2 was induced by the lower dose of methanol at 24 h but by the higher one at 96 h. When given together, L-carnitine and methanol (1/2 LD50) significantly stimulated CYP2E1 up to 170% at 24 h and 145% at 96 h.

MeSH terms

  • Administration, Oral
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis*
  • Carnitine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Induction
  • Injections, Intraperitoneal
  • Male
  • Methanol / toxicity*
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • NADPH-Ferrihemoprotein Reductase / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Solvents / toxicity*
  • Time Factors
  • Vitamin B Complex / therapeutic use*

Substances

  • Solvents
  • Vitamin B Complex
  • Aryl Hydrocarbon Hydroxylases
  • NADPH-Ferrihemoprotein Reductase
  • Carnitine
  • Methanol