Effects of in utero administration of alcohol on glutathione levels in brain and liver.
Previous studies in our laboratory have shown that the ontogenic development of gamma-glutamyltranspeptidase (gamma-GTP) activity is delayed by the in utero administration of alcohol. gamma-GTP is responsible for the degradation and recycling of glutathione (GSH) via the gamma-glutamyl cycle. In this study, we examined the effects of the in utero administration of alcohol on GSH levels in gestational age 21-day-old (g21) rats. Pregnant rats were placed on a liquid diet containing either 35% ethanol-derived calories (35% EDC) or a pair-fed (PF) diet or a lab chow (LC) diet starting on day 1 of gestation and maintained on their respective diets until gestational day 21. On gestational day 21, the pups were delivered by Cesarean section and brains and livers removed and prepared for analysis of GSH, gamma-GTP, or gamma-glutamyl-cysteine synthetase (gamma-GCSyn). GSH levels in brain and liver were found to be significantly lower in the offspring of the 35% EDC-treated mothers than from the PF and LC controls. gamma-GTP activity was higher in brain and liver of the 35% EDC group than the PF group. gamma-GCSyn, the enzyme involved in the rate-limiting step of GSH synthesis, was not affected in liver, but was found to be decreased in brain of the 35% EDC and PF groups when compared with the LC group. GSH is involved in many cellular reactions that appear to protect the cell from damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Reyes
E
E
Department of Pharmacology, School of Medicine, University of New Mexico, Albuquerque 87131.
Ott
S
S
Robinson
B
B
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000493:pharmacokinetics; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000431:Ethanol; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione