title: Protective effects of dioscin against alcohol-induced liver injury.
abstract: Our previous studies have shown that dioscin has protective effect against liver injury. However, the action of the compound against ethanol-induced liver injury is still unknown. In the present paper, ethanol-induced acute and chronic liver damage rat models were used, and the results showed that dioscin significantly alleviated liver steatosis, reduced the levels of alanine aminotransferase, aspartate aminotransferase, total triglyceride (TG), total cholesterol and malondialdehyde, and increased the levels of high-density lipoprotein, superoxide dismutase, glutathione and glutathione peroxidase. Transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays showed that dioscin prevented mitochondrial ultrastructural alterations and apoptosis caused by ethanol. In addition, dioscin significantly inhibited ethanol-induced cytochrome P450 2E1 activation, down-regulated the levels of mitogen-activated protein kinases phosphorylation, inhibited the expressions of nuclear factor kappa B, glucose regulated protein 78, activating transcription factor 6 and alpha subunit of translation initiation factor 2 to attenuate oxidative damage, decreased the expressions of tumor necrosis factor alpha and interleukin-6, and down-regulated the expressions of apoptosis-related proteins including p53, caspase-3, caspase-9, poly (ADP-ribose)-polymerase and cytokeratin-18. Further investigation indicated that dioscin markedly increased the expressions of peroxisome proliferators-activated receptor α and its target genes including medium-chain acyl-CoA dehydrogenase, carnitine palmitoyl-CoA transferase I and acyl-CoA oxidase to advance fatty acid β-oxidation, up-regulated the expressions of acyl-CoA synthetase long-chain family member 1, acyl-CoA synthetase long-chain family member 5, alpha-aminoadipic semialdehyde dehydrogenase and acyl-CoA dehydrogenase to promote fatty acid metabolism, and down-regulated the expressions of glycerol-3-phosphate acyltransferase, diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 to accelerate TG synthesis. However, dioscin had no effects on the expressions of sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase 1 associated with fatty acid synthesis. In conclusion, dioscin shows excellent protective effect against ethanol-induced liver injury through ameliorating ethanol-induced oxidative stress, mitochondrial function, inflammatory cytokine production, apoptosis and liver steatosis, which should be developed as a new drug for the treatment of ethanol-induced liver injury in the future.
authors.affiliation: College of Pharmacy, Dalian Medical University, 9 Western Lvshun South Road, Dalian, 116044, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.forename: Lingli
authors.initials: L
authors.lastname: Zheng
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism / Q000648:ultrastructure; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D005227:Fatty Acids; D020011:Protective Agents; C019357:dioscin; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D004144:Diosgenin