Chronic binge ethanol-mediated acidemia reduces availability of glutamine and related amino acids in maternal plasma of pregnant sheep

Ramadoss, Jayanth; Wu, Guoyao; Cudd, Timothy A.

doi:10.1016/j.alcohol.2008.08.008

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Volume 42, Issue 8 , Pages 657-666, December 2008

Chronic binge ethanol-mediated acidemia reduces availability of glutamine and related amino acids in maternal plasma of pregnant sheep

Jayanth Ramadoss
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Highway 60, Boulevard VMA, Room 332, College Station, TX 77843, USA
- Michael E. DeBakey Institute, Texas A&M University, Highway 60, Boulevard VMA, Room 332, College Station, TX 77843, USA
Guoyao Wu
- Department of Animal Science and Faculty of Nutrition, Texas A&M University, Highway 60, Boulevard VMA, Room 332, College Station, TX 77843, USA
Timothy A. Cudd
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Highway 60, Boulevard VMA, Room 332, College Station, TX 77843, USA
- Michael E. DeBakey Institute, Texas A&M University, Highway 60, Boulevard VMA, Room 332, College Station, TX 77843, USA
- Corresponding author. Tel.: +1-979-862-1972; fax: +1-979-845-6544.

Received 4 March 2008; received in revised form 29 July 2008; accepted 18 August 2008.

Abstract

Heavy drinking during pregnancy can result in fetal alcohol syndrome (FAS), of which, fetal and postnatal growth retardation and central nervous system deficits are cardinal features. Although a number of mechanisms have been proposed, none fully account for these deficiencies. We have previously reported that maternal ethanol exposure (1.75g/kg) results in transient acidemia in the mother and fetus. Alterations in pH are known to regulate glutamine homeostasis. Therefore, we hypothesized that chronic binge ethanol-mediated acidosis reduces glutamine concentrations in maternal plasma that result in decreases in the circulating levels of amino acids related to glutamine metabolism. Pregnant ewes were divided into three groups: ethanol (1.75g/kg), saline control, and acidemia (inspired fractional carbon dioxide [CO₂] was manipulated to mimic the maternal arterial pH pattern created by ethanol). The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109, continuing to GD 132. Plasma samples were analyzed for nutrients and metabolites using HPLC and spectrophotometric methods.

Maternal plasma concentrations of glutamate increased (58%), whereas glutamine, citrulline, and arginine decreased (between 14 and 53%) in response to an acute challenge after the chronic exposure in ethanol-treated ewes. No differences in these amino acid concentrations were noted between the ethanol and acidemic group subjects. Maternal plasma lactate levels increased by ∼100% in response to ethanol, whereas glucose and urea levels did not change in any group. We conclude that maternal chronic binge ethanol consumption results in acidosis-mediated reductions in circulating levels of glutamine and related amino acids that could be responsible for neuronal deficits, altered fetal growth, development, and programming. We also speculate that the consequent increase in fetal glutamate during critical periods of brain development may contribute to the pathogenesis of FAS.

Keywords: FAS, FASD, Alcohol, Acidosis, Amino acids, Glutamate