Ergothioneine modulates proinflammatory cytokines and heat shock protein 70 in mesenteric ischemia and reperfusion injury

J Surg Res. 2008 Jan;144(1):36-42. doi: 10.1016/j.jss.2007.04.020. Epub 2007 Jul 2.


Background and aim: Ergothioneine (EGT) is a natural compound that is synthesized by soil bacteria in fungal substrates and exhibits antioxidant functions in many cell models. The purpose of this study was to investigate the effect of EGT on mesenteric ischemia and reperfusion injury.

Materials and methods: Rats were supplemented with or without l-ergothioneine (10 mg/kg/d) for 15 days prior to intestinal ischemia. Animals were subjected to ischemia induced by clamping the superior mesenteric artery for 60 min followed by reperfusion. Serum tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels, tissue malondialdehide (MDA), myleoperoxidase (MPO), and heat shock protein (HSP) 70 levels, as well as histological findings, were evaluated after 1, 2, and 4 h of reperfusion.

Results: Serum TNF-alpha and IL-1beta levels, and tissue MDA and MPO activities at 1, 2 and 4 h after reperfusion in the EGT group, were significantly lower than the control group (P < 0.05). Tissue HSP-70 levels of the study group were significantly greater than the control group at any time point of reperfusion. No significant differences in tissue damage including morphological changes ranging from villous denudation to focal necrosis, ulceration, hemorrhage, and architectural disintegration at 1 and 2 h after reperfusion exist between the two groups; however, after 4 h of reperfusion, the tissue damage based on histopathologic scores by Chiu was considerably lower in the study group (P < 0.05). After 4 h of reperfusion, focal epithelial lifting and occasional areas of denuded villi could be seen in the samples of the treated animals, thus preserving villous height and mucosal architecture.

Conclusion: EGT attenuates mesenteric ischemia reperfusion injury in rat intestine by increasing tissue HSP-70 and decreasing TNF-alpha, IL-1beta, MDA, and MPO levels. EGT also improves morphological alterations, which occurred after IR injury after prolonged periods of reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Ergothioneine / pharmacology*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Interleukin-1beta / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestines / blood supply
  • Intestines / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control
  • Splanchnic Circulation
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antioxidants
  • HSP70 Heat-Shock Proteins
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Ergothioneine
  • Peroxidase