title: Protective effect of Aplysin on hepatic injury in ethanol-treated rats.
abstract: This study evaluated the protective effects of Aplysin against ethanol-induced hepatic injury in rats and analyzed the associated mechanisms. Rats were administered orally with ethanol 8-12 ml/kg bw excluding the rats in the control group at 1h after rats were administered by gavage doses of Aplysin (50, 100, and 150 mg/kg bw) every day. After 6 weeks, rats were sacrificed, and liver injury was evaluated by biochemical and pathological examination. Hepatocyte apoptosis was analyzed by annexin V-FITC/PI staining. Ethanol metabolic enzymes, oxidative stress, mitochondrial function, and Bcl-2, Bax, cytochrome c and cleaved caspase-3 expressions were evaluated by western blot analysis. These results demonstrated that Aplysin exhibited a significant hepatoprotective effect. In the ethanol-treated group, cytochrome P4502E1 and alcohol dehydrogenase were increased significantly in liver tissue. Moreover, Aplysin not only significantly reversed the ratio of NAD(+)/NADH and mitochondrial glutathione depletion, but also reversed the decreased activity of mitochondrial respiratory chain complexes I, III and IV. Overexpression of cytoplasmic cytochrome c and caspase-3 activation was suppressed by Aplysin. These results suggest that Aplysin alleviates hepatocyte apoptosis by modulating the ethanol-metabolizing pathway, attenuating oxidative stress, ameliorating mitochondrial function, inhibiting mitochondrial damage-mediated apoptosis, which ultimately prevent and repair alcoholic liver injury.
authors.affiliation: The Institute of Human Nutrition, Medical College of Qingdao University, 38 Dengzhou Road, Qingdao 266021, PR China. Electronic address: zwlmike@126.com.
authors.forename: Na
authors.initials: N
authors.lastname: Ge
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ai-guo
authors.initials: AG
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Han
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D006842:Hydrocarbons, Brominated; D020011:Protective Agents; D012717:Sesquiterpenes; D000431:Ethanol; D045304:Cytochromes c; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D005978:Glutathione; C000592510:aplysin
keywords: Aplysin; Apoptosis; CAT; CYP2E1; Cyt c; Cytochrome c; GSH; GSH-PX; MRC I, III and IV; Mitochondrial respiratory chain complexes I, III and IV; Mitochondrion; NAD(+); NADH; Oxidative stress; SOD2; catalase; cytochrome P4502E1; cytochrome c; glutathione; glutathione peroxidase; manganese superoxide dismutase; nicotinamide-adenine dinucleotide; reduced form of nicotinamide-adenine dinucleotide