INDUCTION OF RAT HEPATIC MIXED-FUNCTION OXIDASES BY ACETONE AND OTHER PHYSIOLOGICAL KETONES - THEIR ROLE IN DIABETES-INDUCED CHANGES IN CYTOCHROME P450 PROTEINS

CR Barnett, L Petrides, J Wilson, Peter Flatt, C Ioannides

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31 Citations (Scopus)

Abstract

1. To evaluate the role of ketone bodies in diabetes-induced changes in hepatic cytochrome P450 composition, rats were treated with acetone, 3-hydroxybutyrate or 1,3-butanediol. 2. Treatment with acetone enhanced the rat hepatic 0-dealkylations of ethoxyresorufin and methoxyresorufin, and the hydroxylation of p-nitrophenol, but had no effect on lauric acid hydroxylation and ethylmorphine N-demethylation. Neither 3-hydroxybutyrate nor 1,3-butanediol modulated the metabolism of the above substrates. 3. Immunoblot analysis of hepatic microsomal proteins revealed that treatment with acetone increased the apoprotein levels of P4501A2, P4502B1/2 and P4502E1. 4. It is concluded that acetone is responsible, at least partly, for the diabetes-induced increase in hepatic microsomal P4501A2, P4502B1/2 and P4502E1 proteins but does not mediate the increases in the P4503A1 and P4504A1 proteins. On the basis of work from our own and other laboratories a mechanism for the diabetes-induced changes in hepatic cytochrome P450 proteins is proposed.
Original languageEnglish
Pages (from-to)1441-1450
JournalXenobiotica
Volume22
Issue number12
Publication statusPublished - Dec 1992

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