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407 ETHANOL CONSUMPTION INCREASES SYSTEMIC OXIDATIVE STRESS IN THE GRAVID GUINEA PIG
  1. P. Young,
  2. X. D. Ping,
  3. L. A.S. Brown,
  4. T. W. Gauthier
  1. Division of Neonatal-Perinatal Medicine, Emory University

Abstract

Background Maternal alcohol abuse remains a significant problem for our society and ˜ 35% of women consume alcohol during pregnancy. Alcohol-induced injury is augmented in females compared to males. Although in utero alcohol exposure is known to increase oxidative stress in the developing fetus, the effects of alcohol use on the gravid female have not been thoroughly explored. Previous studies from our laboratory have demonstrated that in utero ethanol (ETOH) exposure increased fetal oxidative stress in part via a decrease in the availability of the antioxidant glutathione (GSH). We hypothesize that alcohol used during pregnancy increases oxidative stress and alters cytokines in the gravid female.

Objective To 1) evaluate the effects of ETOH consumption on maternal markers of oxidative stress and proinflammatory cytokines and 2) evaluate the effects of GSH supplementation during ETOH ingestion in the gravid female.

Methods Using a guinea pig model of fetal ETOH exposure, timed-pregnant guinea pigs were randomly assigned on ˜ d32 (term d70) to ± ETOH in drinking water up to 4% (25% calories + 8 mg/100 mL saccharin) by d40 gestation. Where appropriate the GSH donors SAM or NAC were added to the water containing the ETOH. Cesarean section was performed on d55 of gestation and maternal blood obtained. Malonyldialdehyde (MDA) a marker of oxidative stress, and the proinflammatory cytokines TNF-α and IL-6 were measured with commercially available ELISAs with values normalized to plasma protein. Values are mean (pg/μg protein) ± SEM.

Results MDA was significantly increased with ETOH consumption (control 0.0142 ± 0.001, ETOH 0.0285 ± 0.00329, p < .05, n = 3). The level of MDA was normalized with the addition of SAM or NAC during ETOH ingestion (NAC 0.0156 ± 0.00263 vs. SAM 0.0166 ± 0.00201, p < .05 respectively, n = 3). In preliminary studies, plasma TNF-α was nearly doubled and IL-6 increased by 60% in the ethanol dam. The addition of SAM or NAC blunted this increase of proinflammatory cytokines.

Conclusions ETOH consumption during pregnancy increases systemic oxidative stress in the female dam. The addition of GSH donors during ETOH ingestion protects the dam from ETOH-induced oxidant stress. We speculate that alcohol ingestion during pregnancy increases the risk of oxidant and proinflammatory mediated injury in the female. Funded by NIH RO1 AA013972-02 (to T.W.G.).

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