Ethanol-induced oxidative stress and enzymatic defenses in cultured fetal rat hepatocytes.
Previously, we have documented an ethanol (E)-induced oxidative stress (OS) in cultured fetal rat hepatocytes (FRH). The cause of this is uncertain, but an inhibition of key antioxidant enzymes could be a/the factor. OS was also observed in fetal liver (FL) during in utero E exposure, but not in maternal liver, a difference that might be related to selectively lower enzymatic defenses in the fetus. Here, we record effects of E on activities of catalase (Cat), superoxide dismutase (Cu, Zn SOD and Mn SOD), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) in FRH isolated from 20-day-old fetuses and exposed to E (2 mg/ml) for up to 24 h and we compare these to adult rat liver data. E treatment decreased fetal liver reduced glutathione (GSH) pools by 23% (p < 0.05) and increased malondialdehyde (MDA) by 14% (p < 0.05) within 24 h of E exposure. E caused an increase in fetal liver Cat by 18%, 32%, and 47% by 3, 6, and 24 h of E, respectively (p < 0.05). A 24-h E exposure increased Cu, Zn SOD by 22% (p < 0.05) and Mn SOD by 21% (p < 0.05). A 24 h E treatment increased GPX by 18% (p < 0.05) and GST by 17% (p < 0.05). Cat in whole FL was 26% of adult (p < 0.05) whereas Cu, Zn SOD and Mn SOD in whole FL were 12% and 11% of adult levels (p < 0.05). GPX and GST in FL were 11% and 28% of adult values (p < 0.05). It is concluded that in FRH, E-induced OS is not caused by impaired activities of these enzymes, but their low basal activities (vs. adult) may predispose the fetus to OS.
Devi
B G
BG
University of Texas Health Science Center at San Antonio, Department of Medicine 78284-7878, USA.
Schenker
S
S
Mazloum
B
B
Henderson
G I
GI
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000431:Ethanol; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione