Effect of 1,3-butanediol on rat liver microsomal NDMA demethylation and other monooxygenase activities.

The administration of 1,3-butanediol (BD) previously has been shown to elevate blood concentrations of ketone bodies, to potentiate carbon tetrachloride hepatotoxicity, and to increase the hepatic microsomal content of cytochrome P450 and the activity of aniline hydroxylase. In the present study, oral treatment (10 g/kg) with racemic BD and each of its enantiomers (R-BD and S-BD) induced NDMA demethylase activity by approx. 1.5-fold in rat hepatic microsomes obtained 12 h later, suggesting an induction of P450IIE1, the acetone/ethanol-inducible form of P450. The results agreed with an immunochemically determined increase in the levels of this isozyme. No change in P450 content, NADPH-cytochrome-c reductase, or in pentoxyresorufin dealkylase activity were detected. Blood levels of acetone were determined during a 10-h period after BD administration and showed a higher initial rate of increase by R-BD, possibly due to steroselective metabolic oxidative metabolism. However, no difference in the induction of NDMA demethylase activity by the enantiomers could be detected. Induction of P450IIE1 probably contributes to the previously described potentiation of haloalkane-induced hepatotoxicity by BD administration.