Malotilate, a hepatoprotectant, suppresses CYP2E1 expression in rats

Biochem Biophys Res Commun. 1994 May 16;200(3):1414-20. doi: 10.1006/bbrc.1994.1608.

Abstract

The expression of CYP2E1 was examined in hepatic tissue from rats treated with malotilate (MT), a hepatoprotectant. Microsomal p-nitrophenol hydroxylase activity in MT-treated rats was decreased to 66% and 47% of control activity at day 2 and 3 post-treatment. SDS-PAGE and immunoblot analyses of hepatic microsomes prepared from MT-treated rats showed that CYP2E1 levels were decreased below the limit of detectability. In contrast, CYP2B1 levels were increased in MT-treated microsomes, as assessed by immunoblot analyses. MT, however, failed to modulate CYP1A expression. RNA hybridization analysis revealed that CYP2E1 mRNA levels failed to change significantly by day 2 or 3 post-treatment, whereas microsomal epoxide hydrolase mRNA levels were elevated approximately 3-fold at the same time points. These results demonstrate that MT effectively suppresses CYP2E1 expression in the absence of transcriptional inactivation.

MeSH terms

  • Animals
  • Base Sequence
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA Primers / chemistry
  • Gene Expression / drug effects
  • Liver / drug effects*
  • Male
  • Malonates / pharmacology*
  • Microsomes, Liver / enzymology
  • Molecular Sequence Data
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • DNA Primers
  • Malonates
  • RNA, Messenger
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Oxidoreductases, N-Demethylating
  • diisopropyl 1,3-dithiol-2-ylidenemalonate