The effects of pregnancy on ethanol clearance

被引:29
作者
Badger, TM
Hidestrand, M
Shankar, K
McGuinn, WD
Ronis, MJ
机构
[1] Univ Arkansas Med Sci, Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA
[2] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72202 USA
[3] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72202 USA
关键词
pregnancy; ethanol; pharmacokinetics; ADH; ALDH; CYP2E1;
D O I
10.1016/j.lfs.2005.02.019
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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/kg(75)/d] or the normal calories required for non-pregnant rats [ 187 kcal/kg(75)/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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:2111 / 2126
页数:16
相关论文
共 55 条
[21]  
JOHANSSON I, 1985, FEBS LETT, V183, P2467
[22]  
Keiver K, 1997, ALCOHOL CLIN EXP RES, V21, P1612
[23]   Appropriate use and misuse of blood concentration measurements to quantitate first-pass metabolism [J].
Levitt, MD ;
Levitt, DG .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 2000, 136 (04) :275-280
[24]  
LEVITT MD, 1994, J PHARMACOL EXP THER, V269, P297
[25]  
Lieber C S, 1994, Alcohol Alcohol Suppl, V2, P163
[26]   PERSPECTIVES - DO ALCOHOL CALORIES COUNT [J].
LIEBER, CS .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1991, 54 (06) :976-982
[27]  
LIEBER CS, 1989, ALCOHOL ALCOHOLISM, V24, P197
[28]  
LINDROS KO, 1996, J PHARM EXPT THERAPE, V275, P79
[29]   PHARMACOKINETICS OF ETHANOL IN THE GUINEA-PIG [J].
LITVIN, J ;
SWITZER, BR .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1988, 12 (01) :71-76
[30]   QUANTITATIVE CORRELATION OF ETHANOL ELIMINATION RATES INVIVO WITH LIVER ALCOHOL-DEHYDROGENASE ACTIVITIES IN FED, FASTED AND FOOD-RESTRICTED RATS [J].
LUMENG, L ;
BOSRON, WF ;
LI, TK .
BIOCHEMICAL PHARMACOLOGY, 1979, 28 (09) :1547-1551