In utero ethanol exposure elicits oxidative stress in the rat fetus.
Prior studies in our laboratory have shown that exposure of cultured fetal rat hepatocytes to ethanol (E) blocks epidermal growth factor-dependent replication and that this is paralleled by cell membrane damage, mitochondrial dysfunction, membrane lipid peroxidation (LP), and enhanced generation of reactive oxygen species. These measures of E-mediated oxidative stress (OS) were mitigated by treatment with antioxidants, and cell replication could be normalized by maintaining cell glutathione (GSH) pools. We have now extended these studies to an in vivo model. Rats were administered E (4 g/kg, po) at 12-hr intervals on days 17 and 18 of gestation and killed on day 19, 1 hr following a final dose of E (a total of 5 doses). Fetal and maternal brain and liver were assayed for signs of OS. The 2-day in utero E exposure increased membrane LP in fetal brain as evidenced by increased malondialdehyde (MDA) levels from 1.76 +/- 0.12 SE (nMol/mg protein) to 2.00 +/- 0.08 (p < 0.05) and conjugated dienes from 0.230 +/- 0.006 SE (OD223/mg lipid) to 0.282 +/- 0.006 (p < 0.05). In fetal liver, MDA levels increased from 2.39 +/- 0.08 SE (nMol/mg protein) to 2.87 +/- 0.08 (p < 0.05), whereas dienes differed significantly only between ad libitum controls and the E and pair-fed control groups (p < 0.05). E decreased GSH levels in fetal brain by 19%, from 19.88 +/- 0.72 to 16.13 +/- 1.06 (nMol/mg protein) (p < 0.05). A 10% decrease in GSH was seen in fetal liver (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Henderson
G I
GI
Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7878, USA.
Devi
B G
BG
Perez
A
A
Schenker
S
S
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000502:physiology; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D000431:Ethanol; D008315:Malondialdehyde; D005978:Glutathione