Effect of treatment with pyrazine and some derivatives on cytochrome P450 and some enzyme activities in rat liver

Xenobiotica. 1993 Feb;23(2):169-79. doi: 10.3109/00498259309059372.

Abstract

1. The effect of pyrazine and three pyrazine derivatives, namely (methylthio) methylpyrazine (MTMP), 5, 6, 7, 8-tetrahydroquinoxaline (CHP) and 5-methyl-6, 7-dihydro-5'-cyclopentapyrazine (CPP), on hepatic peroxisomal and microsomal enzyme activities have been studied in male Sprague-Dawley rats. MTMP (0.25-2 mmol/kg per day) and the other compounds (1 mmol/kg/day) were administered by i.p. injections for 3 days. 2. None of the test compounds appeared to be peroxisome proliferators as there was no marked effect on hepatic palmitoyl-CoA oxidation, and neither pyrazine nor MTMP induced microsomal lauric acid 12-hydroxylase. 3. In contrast, all four compounds induced hepatic microsomal cytochrome P450-dependent enzyme activities. MTMP induced the metabolism of several mixed-function oxidase substrates including, 7-pentoxyresorufin, 7-benzoxyresorufin, benzphetamine, 4-nitrophenol and aniline, whereas pyrazine induced the metabolism of fewer substrates but including 4-nitrophenol and aniline. 4. By Western immunoblotting MTMP was found to increase levels of CYP2B1 and CYP3A isoenzymes, whereas pyrazine increased CYP2E1. 5. Thus, while pyrazine appears to be mainly a CYP2E inducer, MTMP is a mixed inducer of cytochrome P450 isoenzymes in the CYP2B, CYP3A and CYP2E subfamilies. CPP is probably a CYP2E inducer in rat liver, whereas CHP appears to be a mixed inducer of cytochrome P450 isoenzymes in the CYP2B, CYP3A and CYP2E subfamilies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction
  • Isoenzymes / biosynthesis*
  • Isoenzymes / metabolism
  • Liver / anatomy & histology
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Microbodies / drug effects
  • Mixed Function Oxygenases / drug effects
  • Mixed Function Oxygenases / metabolism
  • Organ Size / drug effects
  • Pyrazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Isoenzymes
  • Pyrazines
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases