Effects of phorone (diisopropylidene acetone), a glutathione (GSH) depletor, on hepatic enzymes involved in drug and heme metabolism in rats: evidence that phorone is a potent inducer of heme oxygenase

Biochem Biophys Res Commun. 1987 May 29;145(1):502-8. doi: 10.1016/0006-291x(87)91349-0.

Abstract

Concomitant with the depletion of glutathione content, phorone (250 mg/kg, ip.) produced a marked increase in heme oxygenase activity, biphasic effect on delta-aminolevulinic acid synthetase activity, and slight decreases in cytochrome P-450 content and aminopyrine demethylase activity in the liver of rats. The increase in heme oxygenase activity evoked by phorone was almost completely blocked by pretreatment of rats with actinomycin D and cycloheximide. Phorone was able to produce the changes in these parameters in a dose-dependent manner. Buthionine sulfoximine, a GSH depletor by inhibition of biosynthesis, failed to affect these hepatic parameters.

MeSH terms

  • 5-Aminolevulinate Synthetase / metabolism*
  • Aminopyrine N-Demethylase / metabolism*
  • Animals
  • Cycloheximide / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dactinomycin / pharmacology
  • Glutathione / antagonists & inhibitors
  • Heme / metabolism*
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Ketones / pharmacology*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Microsomes, Liver / enzymology*
  • Mitochondria, Liver / enzymology
  • Mixed Function Oxygenases / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Solvents

Substances

  • Ketones
  • Solvents
  • Dactinomycin
  • Heme
  • phorone
  • Cytochrome P-450 Enzyme System
  • Cycloheximide
  • Mixed Function Oxygenases
  • Heme Oxygenase (Decyclizing)
  • Aminopyrine N-Demethylase
  • 5-Aminolevulinate Synthetase
  • Glutathione