title: Acute ethanol preexposure promotes liver regeneration after partial hepatectomy in mice by activating ALDH2.
abstract: It is known that chronic ethanol significantly impairs liver regeneration. However, the effect of acute ethanol exposure on liver regeneration remains largely unknown. To address this question, C57Bl6/J mice were exposed to acute ethanol (6 g/kg intragastrically) for 3 days, and partial hepatectomy (PHx) was performed 24 h after the last dose. Surprisingly, acute ethanol preexposure promoted liver regeneration. This effect of ethanol did not correlate with changes in expression of cell cycle regulatory genes (e.g., cyclin D1, p21, and p27) but did correlate with protection against the effect of PHx on indices of impaired lipid and carbohydrate metabolism. Ethanol preexposure protected against inhibition of the oxidant-sensitive mitochondrial enzyme, aconitase. The activity of aldehyde dehydrogenase 2 (ALDH2) was significantly increased by ethanol preexposure. The effect of ethanol was blocked by inhibiting (Daidzin) and was mimicked by activating (Alda-1) ALDH2. Lipid peroxides are also substrates for ALDH2; indeed, alcohol preexposure blunted the increase in lipid peroxidation (4OH-nonenal adducts) caused by PHx. Taken together, these data suggest that acute preoperative ethanol exposure "preconditions" the liver to respond more rapidly to regenerate after PHx by activating mitochondrial ALDH2, which prevents oxidative stress in this compartment.
authors.affiliation: Dept. of Pharmacology and Toxicology, 505 S Hancock St., CTRB, Rm 506, Univ. of Louisville Health Sciences Center, Louisville, KY, 40292. gavin.arteel@louisville.edu.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ding
authors.forename: Juliane I
authors.initials: JI
authors.lastname: Beier
authors.forename: Keegan J
authors.initials: KJ
authors.lastname: Baldauf
authors.forename: Jenny D
authors.initials: JD
authors.lastname: Jokinen
authors.forename: Hai
authors.initials: H
authors.lastname: Zhong
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Arteel
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D019610:Cytoprotection; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006498:Hepatectomy / Q000379:methods*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000154:Aconitate Hydratase
keywords: alcohol; aldehyde dehydrogenase 2; liver regeneration; oxidative stress