Effects of acetone and methyl n-butyl ketone on hepatic mixed-function oxidase.
The administration of ketones potentiates CCl4 hepatotoxicity; however, the potencies of the ketones differ. The aim of the present study was to assess potential differences between acetone and methyl n-butyl ketone (MnBK) on cytochrome P-450. The effects of single and repetitive doses of acetone and MnBK were determined in male rats by estimating the rate of metabolite formation of three substrates and the hepatic content of cytochrome P-450. A single treatment with acetone (13.5 mmol/kg or greater) enhanced the oxidation of aniline and 7-ethoxycoumarin, whereas repetitive treatments also increased aminopyrine demethylation and cytochrome P-450 content. Single and repetitive treatments of MnBK (15 mmol/kg) augmented the oxidation of all three substrates and increased cytochrome P-450 content. The effects of the ketones on cytochrome P-450 isozymes were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Acetone and MnBK increased the 52.1 and 54.1 kD forms and, in addition, MnBK tended to increase the 50.6 kD species. The data indicate that ketones differ in the type of isozymes induced and in the degree of induction. The higher potency of MnBK, compared to acetone, is probably associated with the fact that MnBK affects a greater number of isozymes than acetone.
Kobusch
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Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Plaa
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GL
du Souich
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P
D000096:Acetone / Q000494:pharmacology*; D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000502:physiology; D007527:Isoenzymes / Q000032:analysis*; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000814:Aniline Compounds; D003374:Coumarins; D007527:Isoenzymes; D007659:Ketones; D000632:Aminopyrine; D000096:Acetone; C017299:7-ethoxycoumarin; D008742:Methyl n-Butyl Ketone; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; C023650:aniline