ETHANOL ELIMINATION IN ALCOHOL-TREATED PREGNANT RATS

The effects of chronic intake of alcohol on ethanol elimination were studied in 20-day pregnant rats, in their foetuses, and in virgin rats. Experimental animals received ethanol in drinking water (from 10% to 25% in 2 months) (alcohol group), whereas controls drank only water. At the end of chronic exposure, alcohol dehydrogenase activity was determined in stomach and liver and cytochrome P-450 was measured in liver. In a complementary assay, the same experimental groups of rats were given an acute dose of ethanol (2 g/kg body wt, 25% w/v) either intragastrically or intraperitoneally, at the end of the chronic exposure, to determine first-pass ethanol metabolism and pharmacokinetic parameters of its elimination. Significant differences were found between alcohol and control groups for liver and stomach alcohol dehydrogenase activity in pregnant rats. Only in virgins did chronic alcohol treatment significantly increase the liver cytochrome P-450 content. In virgin rats, the first-pass metabolism of ethanol was lower in the alcohol group than in control. By contrast, in control rats, the first-pass of ethanol was lower in pregnant, than in virgin, rats. The metabolic rate of ethanol elimination (mg/kg body wt/hr) was clearly enhanced in alcoholic virgin rats, demonstrating that this model of chronic alcoholism induces metabolic tolerance to ethanol. In alcoholic pregnant rats, a surprisingly low theoretical volume of body ethanol distribution (55 ml/100 g body wt vs. 80 ml/100 g body wt in the other groups) masked their metabolic tolerance to ethanol. This preliminary study should be taken into account when evaluating the effects of chronic or/and acute alcohol intake during pregnancy on the circulating ethanol levels in foetuses and on future development of the foetal alcohol syndrome.