Abstract
The effect of acute ethanol treatment on hepatic metabolism of hexobarbital (Hb) was studied in the rat. Oral administration of 3 g/kg of ethanol (15% w/v) inhibited Hb hydroxylase activity 45–50 per cent. A dose-response relationship was found for ethanol inhibition of Hb metabolism. The overall hepatic microsomal protein content was not affected, but the hepatic cytochrome P-450 level was reduced approximately 42 per cent by this ethanol treatment. Corticosterone (12.5 mg/kg, i.p.) inhibited Hb hydroxylase activity 43 per cent. The combination of ethanol and corticosterone treatment further inhibited Hb hydroxylase activity. Study in vitro showed that corticosterone inhibited Hb metabolism competitively. Ethanol caused a 3-fold increase in the plasma corticosterone level but had no effect on plasma corticosterone of adrenalectomized rats. Hexobarbital metabolism was not affected by ethanol in adrenalectomized rats. Thus, the inhibition of hepatic Hb metabolism by acute ethanol was caused by the increased release of corticosterone induced by ethanol.
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