Ergothioneine pretreatment protects the liver from ischemia-reperfusion injury caused by increasing hepatic heat shock protein 70

J Surg Res. 2004 Nov;122(1):96-102. doi: 10.1016/j.jss.2004.06.016.


Background: Reperfusion of the liver after ischemia induces the expression of the heat shock genes and the synthesis of the heat shock proteins (HSP). We studied the effects of the natural antioxidant ergothioneine (EGT) treatment on the expression of HSP70 in ischemic-reperfused (IR) liver.

Methods: Adult male Wistar rats were randomly divided into three groups: Sham group given standard laboratory chow and water for 3 weeks followed by sham operation; Control group given standard laboratory chow and water for 3 weeks followed by liver IR injury; EGT group given standard laboratory chow supplementation l-ergothioneine (1.2 mg/kg/d body weight) administered by gavage and water for 3 weeks followed by liver IR injury. Ten rats from each group were killed to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), tissue malondialdehyde (MDA), HSP70 levels, and histologic changes at 30, 60, and 120 min of reperfusion, respectively. Survival was followed for 1 week.

Results: IR caused significant increase in serum AST, ALT, LDH, and tissue MDA levels. As compared with the control group, animals treated with EGT experienced a significant decrease in serum AST, ALT, and LDH levels in all reperfusion periods. Tissue MDA levels in animals receiving EGT were significantly reduced as compared with control group at 30 min and 60 min after reperfusion. After ischemia, reperfusion caused a remarkable production of HSP70 in the control group. When the rats were pretreated with EGT, the levels of HSP70 increased significantly in their livers after reperfusion compared with the control group. Liver injury in the EGT-treated animals was lower to that in the control group. The 7-day survival rate was significantly improved (from 50% to 80%) by EGT pretreatment.

Conclusion: HSP70 has been shown to induce tolerance against warm IR injury in rat livers. EGT pretreatment protects the liver from IR injury by over-expression of HSP and the subsequent suppression of lipid peroxidation.

MeSH terms

  • Alanine Transaminase / antagonists & inhibitors
  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / antagonists & inhibitors
  • Aspartate Aminotransferases / blood
  • Cytoprotection
  • Ergothioneine / pharmacology*
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / metabolism*
  • Immunohistochemistry / methods
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / pathology
  • Liver Circulation*
  • Male
  • Malondialdehyde / antagonists & inhibitors
  • Malondialdehyde / blood
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology*
  • Staining and Labeling
  • Survival Analysis


  • Antioxidants
  • HSP70 Heat-Shock Proteins
  • Malondialdehyde
  • Ergothioneine
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase