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 consumpt ion with mitochondria being the target organelles, This process genera tes a highly reactive and toxic product, 4-hydroxynonenal (HNE), In th e present study, HNE levels and metabolism were assessed in mitochondr ia of fetal and maternal Liver after in vivo ethanol exposure, Female Sprague-Dawley rats received five doses of ethanol (4 g/kg orally at 1 2-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 mitochon dria. 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 dinucleoti de-dependent oxidation, reduced glutathione conjugation, and reduced n icotine adenine dinucleotide-dependent reduction, whereas in fetal liv er only the former two pathways were active, but to a lesser degree th an in adult mitochondria, On the other hand, mitochondria from fetal L iver showed a higher production of HNE when oxidative stress was induc ed with t-butyl hydroperoxide. Prior in vivo ethanol exposure further potentiated HNE formation in t-butyl hydroperoxide-stimulated fetal li ver mitochondria, but not in adult mitochondria. These findings indica te that increased levels of HNE in fetal liver mitochondria after mate rnal ethanol consumption reflect a higher susceptibility to HNE format ion in addition to a lesser capacity to metabolize it, The enhanced ac cumulation of this toxic aldehyde may contribute to oxidative damage o bserved in fetal tissues after in utero ethanol exposure.