Induction of rat hepatic mixed-function oxidases by acetone and other physiological ketones: their role in diabetes-induced changes in cytochrome P450 proteins.
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 O-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.
Barnett
C R
CR
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
Petrides
L
L
Wilson
J
J
Flatt
P R
PR
Ioannides
C
C
D000096:Acetone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D007659:Ketones / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D007659:Ketones; D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases