Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection

• Published in: World Journal of Gastroenterology Vol. 20; no. 48; pp. 18249 - 18259
• Main Author: Liu, Xu
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.12.2014
• Subjects: alcohol; Aldehyde Dehydrogenase 1 Family; Animals; class-1; dehydrogenase; Disease Models, Animal; Etha; Ethanol; Ethanol - blood; Ethanol - pharmacokinetics; Fatty Liver, Alcoholic; Fatty Liver, Alcoholic - etiology; Fatty Liver, Alcoholic - genetics; Fatty Liver, Alcoholic - metabolism; Fatty Liver, Alcoholic - physiopathology; Gene Expression Regulation; Hepatectomy; Hepatectomy - adverse effects; Hepatic; Isoenzymes; Isoenzymes - genetics; Isoenzymes - metabolism; Lipid Metabolism; Lipid Metabolism - genetics; Liver; Liver - metabolism; Liver - physiopathology; Liver Regeneration; Male; Metabolic Clearance Rate; Original; Rats, Wistar; Recovery of Function; Retinal Dehydrogenase; Retinal Dehydrogenase - genetics; Retinal Dehydrogenase - metabolism; Risk Factors; RNA, Messenger; RNA, Messenger - metabolism; Hepatic class-1 alcohol dehydrogenase; Liver function; Liver resection; Hepatic steatosis; Ethanol; Ethanol elimination
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v20.i48.18249

AIM:To investigate ethanol-induced hepatic steatosis after liver resection and the mechanisms behind it.METHODS:First,the preliminary examination was performed on 6 sham-operated(Sham)and 30 partial hepatectomy(PH)male Wistar rats(8-wk-old)to evaluate the recovery of the liver weight and liver function after liver resection.PH rats were sacrificed at the indicated time points(4,8,and 12 h;1,3,and 7d)after PH.Second,the time point for the beginning of the chronic ethanol exposure(1 wk after sham-or PH-operation)was determined based on the results of the preliminary examination.Finally,pair-feeding was performed with a controlled diet or with a 5-g/d L ethanol liquid diet for 28 d in another 35 age-matched male Wistar rats with a one-week recovery after undergoing a sham-(n=15)or PH-operation(n=20)to evaluate the ethanol-induced liver injury after liver resection.Hepatic steatosis,liver function,fatty acid synthase(Fas)gene expression level,the expression of lipid metabolism-associated enzyme regulator genes[sterol regulatory element binding protein(Srebp)-1and pe roxis ome prol i fe rat or-ac t ivat e d re c e pt or(Ppar)-α],the mediators that alter lipid metabolism[plasminogen activator(Pai)-1 gene expression level and tumor necrosis factor(Tnf)-αproduction],and hepatic class-1 alcohol dehydrogenase(Adh1)-associated ethanol elimination were investigated in the4 groups based on histological,immunohistochemical,biochemical,Western blotting,reverse transcriptase chain reaction,and blood ethanol concentration analyses.The relevant gene expression levels,liver weight,and liver function were assessed before and 1wk after surgery to determine the subject’s recovery from the liver resection using the rats that had been subjected to the preliminary examination.RESULTS:In the PH rats,ethanol induced marked hepatic steatosis with impaired liver functioning,as evidenced by the accumulation of fatty droplets within the hepatocytes,the higher increases in their hepatic triglyceride and blood alanine aminotransferase and blood aspartate aminotransferase levels after the 28-d pair-feeding period.The Sham-ethanol rats,not the PH-ethanol rats,demonstrated the up-regulation of Srebp-1 and the down-regulation of Ppar-αm RNA expression levels after the 28-d pair-feeding period.The 28-d ethanol administration induced the upregulation of Pai-1 gene expression level and an overproduction of TNF-αin the Sham and the PH rats;however,the effect was more significant in the PH rats.The PH-ethanol rats(n=4)showed higher residual blood ethanol concentrations than did the Sham-ethanol rats(n=6)after a 5-h fast(0.66±0.4 mg/m L vs 0.2±0.1 mg/m L,P<0.05);these effects manifested without up-regulation of Adh1 gene expression,which was present in the Sham-ethanol group after the 28-d pair-feeding period.One week after the liver resection,the liver weight,function,the gene expression levels of Fas,Srebp-1,Ppar-α,Pai-1 and Tnf-αrecovered;however,the Adh1 gene expression did not recover in rats.CONCLUSION:Desensitization to post-hepatectomy ethanol treatment and slow recovery from PH in Adh1gene expression enhanced the susceptibility to ethanolinduced hepatic steatosis after PH in rats.