Ergothioneine Modulates Proinflammatory Cytokines and Heat Shock Protein 70 in Mesenteric Ischemia and Reperfusion Injury

Sakrak, Omer; Kerem, Mustafa; Bedirli, Abdulkadir; Pasaoglu, Hatice; Akyurek, Nalan; Ofluoglu, Ebru; Gültekin, Fatma Ayça

doi:10.1016/j.jss.2007.04.020

« Previous Next »Journal of Surgical Research
Volume 144, Issue 1 , Pages 36-42, January 2008

Ergothioneine Modulates Proinflammatory Cytokines and Heat Shock Protein 70 in Mesenteric Ischemia and Reperfusion Injury

Omer Sakrak, M.D.
- Department of General Surgery, Gazi University, School of Medicine, Ankara, Turkey
Mustafa Kerem, M.D.
- Department of General Surgery, Gazi University, School of Medicine, Ankara, Turkey
- To whom correspondence and reprint requests should be addressed at Department of General Surgery, Faculty of Medicine, Gazi University, 06510 Besevler, Ankara, Turkey.
Abdulkadir Bedirli, M.D.
- Department of General Surgery, Gazi University, School of Medicine, Ankara, Turkey
Hatice Pasaoglu, M.D.
- Department of Biochemistry, Gazi University, School of Medicine, Ankara, Turkey
Nalan Akyurek, M.D.
- Department of Pathology, Gazi University, School of Medicine, Ankara, Turkey
Ebru Ofluoglu, Ph.D.
- Department of Biochemistry, Gazi University, School of Medicine, Ankara, Turkey
Fatma Ayça Gültekin, M.D.
- Department of General Surgery, Gazi University, School of Medicine, Ankara, Turkey

Received 5 October 2006 published online 09 July 2007.

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)-α and interleukin-1β (IL-1β) 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-α and IL-1β 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-α, IL-1β, MDA, and MPO levels. EGT also improves morphological alterations, which occurred after IR injury after prolonged periods of reperfusion.

Key Words: mesenteric ischemia, reperfusion, ergothioneine, cytokines, heat shock protein