4-hydroxynonenal levels are enhanced in fetal liver mitochondria by in utero ethanol exposure.
Lipid peroxidation has been implicated in ethanol-induced liver injury and observed in fetal liver and brain after maternal ethanol consumption with mitochondria being the target organelles. This process generates a highly reactive and toxic product, 4-hydroxynonenal (HNE). In the present study, HNE levels and metabolism were assessed in mitochondria of fetal and maternal liver after in vivo ethanol exposure. Female Sprague-Dawley rats received five doses of ethanol (4 g/kg orally at 12-hour intervals) and were killed on day 19 of gestation. The results showed that HNE levels were enhanced in hepatic mitochondria of fetal rats exposed to ethanol, far in excess of that in adult liver mitochondria. Measurement of HNE metabolism showed that fetal mitochondria had a lower capacity for HNE catabolism than adult mitochondria. In adult mitochondria, HNE could be metabolized by nicotine adenine dinucleotide-dependent oxidation, reduced glutathione conjugation, and reduced nicotine adenine dinucleotide-dependent reduction, whereas in fetal liver only the former two pathways were active, but to a lesser degree than in adult mitochondria. On the other hand, mitochondria from fetal liver showed a higher production of HNE when oxidative stress was induced with t-butyl hydroperoxide. Prior in vivo ethanol exposure further potentiated HNE formation in t-butyl hydroperoxide-stimulated fetal liver mitochondria, but not in adult mitochondria. These findings indicate that increased levels of HNE in fetal liver mitochondria after maternal ethanol consumption reflect a higher susceptibility to HNE formation in addition to a lesser capacity to metabolize it. The enhanced accumulation of this toxic aldehyde may contribute to oxidative damage observed in fetal tissues after in utero ethanol exposure.
Chen
J J
JJ
Division of Gastroenterology and Nutrition, Department of Medicine, The University of Texas Health Science Center at San Antonio, 78284-7878, USA.
Schenker
S
S
Henderson
G I
GI
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D015227:Lipid Peroxidation; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D009243:NAD; D000431:Ethanol; C027576:4-hydroxy-2-nonenal