The effects of pregnancy on ethanol clearance.
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.
Badger
Thomas M
TM
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. BadgerThomasM@uams.edu
Hidestrand
Mats
M
Shankar
Kartik
K
McGuinn
W David
WD
Ronis
Martin J
MJ
D000284:Administration, Oral; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008657:Metabolic Clearance Rate; D011247:Pregnancy / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1