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.
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.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism*; D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D005978:Glutathione / Q000037:antagonists & inhibitors; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents
D007659:Ketones; D012997:Solvents; D003609:Dactinomycin; D006418:Heme; C018637:phorone; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D000633:Aminopyrine N-Demethylase; D000624:5-Aminolevulinate Synthetase; D005978:Glutathione