title: Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis.
abstract: BACKGROUND
  Dioscin shows potent effects against liver damage in our previous studies; however, the action of it on hepatic ischemia-reperfusion (I/R) injury is still unknown. In the present article, the effects and possible mechanisms of dioscin against hepatic I/R injury were investigated.
  
  
  METHODS
  Seventy percent partial hepatic warm ischemia was induced in Wistar rats for 60 min followed by succedent reperfusion. In the prophylactic test, dioscin was administered intragastrically to the rats at doses of 20, 40, and 60 mg/kg once daily for seven consecutive days before I/R. In the therapeutic test, the rats received dioscin intragastrically at a dose of 60 mg/kg once 2 hr before I/R.
  
  
  RESULTS
  We found that dioscin significantly decreased serum alanine aminotransferase and aspartate aminotransferase activities, increased survival rate of rats, and improved I/R-induced hepatocyte abnormality. In addition, dioscin obviously increased the levels of SOD, CAT, GSH-Px, GSH, decreased the levels of MDA, TNOS, iNOS, NO, and prevented DNA fragmentation caused by I/R injury. Further research indicated that dioscin markedly decreased the gene expressions of interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, MIP-1α, MIP-2, Fas, FasL, decreased the protein expressions of NF-κB, AP-1, COX-2, HMGB-1, CYP2E1, Bak, caspase-3, p53, PARP, Caspase-9, decreased the levels of JNK, ERK and p38 MAPKs phosphorylation, and upregulated the levels of Bcl-2 and Bcl-x.
  
  
  CONCLUSIONS
  Our results suggest that dioscin has potent actions against hepatic I/R injury through suppression of inflammation, oxidative-nitrative stress, and apoptosis, which should be developed as a new drug to treat hepatic I/R injury in the future.
authors.affiliation: 1 College of Pharmacy, Dalian Medical University, Liaoning Province, China. 2 Department of Critical Care Medicine of the First Affiliated Hospital of Dalian Medical University, Dalian, China. 3 Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Dalian, China. 4 Address correspondence to: Jinyong Peng, M.D., College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Tao
authors.forename: Xianyao
authors.initials: X
authors.lastname: Wan
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation; D008099:Liver / Q000293:injuries*; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013997:Time Factors; D052096:Warm Ischemia
chemical_list: D000975:Antioxidants; C019357:dioscin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004144:Diosgenin; D009584:Nitrogen