Triptolide alleviates hepatic ischemia/reperfusion injury by attenuating oxidative stress and inhibiting NF-κB activity in mice

J Surg Res. 2011 Apr;166(2):e205-13. doi: 10.1016/j.jss.2010.10.005. Epub 2010 Nov 4.

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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • I-kappa B Proteins / metabolism
  • Immunosuppressive Agents / pharmacology
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Liver Diseases / drug therapy*
  • Liver Diseases / immunology
  • Liver Diseases / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neutrophils / immunology
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Phenanthrenes / pharmacology*
  • RNA, Messenger / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / metabolism
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Diterpenes
  • Epoxy Compounds
  • I-kappa B Proteins
  • Immunosuppressive Agents
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Nfkbia protein, mouse
  • Phenanthrenes
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • triptolide
  • Malondialdehyde
  • Peroxidase
  • Aspartate Aminotransferases
  • Alanine Transaminase