Submitted to: Life Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2005
Publication Date: 9/9/2005
Citation: Badger, T.M., Hidestrand, M., Shankar, K., Mcguinn, W.D., Ronis, M.J. 2005. The effects of pregnancy on ethanol clearance. Life Sciences. 77(17):2111-2126.
Interpretive Summary: Despite a wealth of publicity warning women of the dangers of drinking alcohol during pregnancy, a surprisingly large number of expecting women consume ethanol. Alcohol can do permanent damage to developing fetal tissue and this damage depends on the dose of alcohol reaching the fetus. Interestingly, the number of fetal alcohol syndrome children is far less than would be predicted by the number of women who consume alcohol during pregnancy. For a given alcohol intake, the concentration reaching the fetus is determined by how fast the alcohol is metabolized or cleared from the body. Therefore, we hypothesized that pregnant women clear alcohol faster than non-pregnant women and the increased caloric intake was in part responsible. In this study we demonstrated that pregnant rats clear or metabolize alcohol faster than non-pregnant rats, but this did not appear to be due to caloric intake. This resulted in a lower circulating alcohol level, which would mean that less alcohol would reach the fetus.
Technical Abstract: We have studied the effects of pregnancy on ethanol clearance rates and on blood and urine ethanol concentrations (BECs and UECs) in adult Sprague–Dawley rats infused with ethanol intragastrically. Pregnant rats had greater ethanol clearance following an intragastric or intravenous ethanol bolus (3 or 0.75 g/kg, respectively) relative to non-pregnant rats (p < 0.05). Pregnant rats infused with ethanol-containing diets for several days had lower (p < 0.05) UECs than non-pregnant rats when given the same dose of ethanol. Non-pregnant rats infused ethanol-containing diets at two levels of calories (the higher caloric intake required by pregnant rats [220 kca/kg75/d] or the normal calories required for non-pregnant rats [187 kcal/kg75/d]) had statistically equal UECs, suggesting that increased caloric intake was not responsible for the effect of pregnancy. While the activity of hepatic alcohol dehydrogenase (ADH) did not differ with pregnancy, gastric ADH activity was increased (p < 0.001). Furthermore, total hepatic aldehyde dehydrogenase (ALDH) and hepatic mitrochrondrial protein were increased (p < 0.05) and hepatic CYP2E1 activity was suppressed (p < 0.05). The results suggest that pregnancy increases ethanol elimination in pregnant rats by: 1) induction of gastric ADH; 2) elevated hepatic ALDH activity; and 3) increased mitochondrial respiration. The greater ethanol clearance results in lower tissue ethanol concentrations achieved during pregnancy for a given dose, and this may have clinical significance as a mechanism to protect the growing fetus from ethanol toxicity.