title: Triptolide alleviates hepatic ischemia/reperfusion injury by attenuating oxidative stress and inhibiting NF-κB activity in mice.
abstract: BACKGROUND
  Hepatic I/R injury is unavoidable in liver transplantation and surgery. This remains a significant problem in surgical procedures. The purpose of this study was to investigate the effects of triptolide on liver ischemia/reperfusion (I/R) injury and related mechanisms in mice.
  
  
  METHODS
  Male C57BL/6 mice were randomized into four groups: (1) sham group; (2) sham-triptolide group; (3) I/R group; and (4) I-R/triptolide group. Ninety minutes of warm ischemia was induced and flow by 24 h reperfusion. Serum alanine aminotransferase and aspartate aminotransferase were assayed, pathologic alterations and (NF)-κB p65 immunohistochemistry were observed. Liver malondialdehyde (MDA) level, activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and activity of neutrophil accumulation marker myeloperoxidase (MPO) were measured. TNF-α, IL-6, and IL-1β mRNA were detected by RT-PCR, whereas nuclear factor (NF)-κB p65 and IκBα were assessed with Western blotting.
  
  
  RESULTS
  Plasma aminotransferase activity was higher in the I/R group than in the I/R-triptolide group. MDA level and neutrophil infiltration were also markedly reduced, while SOD, CAT, and GSH-Px levels increased in I/R-triptolide group compared with I/R group. In group 4, histopathologic changes were significantly attenuated in triptolide-treated livers. In comparison with group 3, triptolide reduced NF-κB p65 nuclear and IκBα expression, and effectively suppressed pro-inflammatory cytokine level during the I/R.
  
  
  CONCLUSIONS
  These results suggest that triptolide has protective effects against hepatic I/R injury. Its mechanisms might be related to reduction of oxidative stress and neutrophil infiltration and inhibition NF-κB p65 activity.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, China.
authors.forename: Chuanxing
authors.initials: C
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Rao
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Wang
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010616:Phenanthrenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C001899:triptolide; D008315:Malondialdehyde; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase