Modulation of palmitic acid-induced cell death by ergothioneine: Evidence of an anti-inflammatory action

Inflammation and reactive oxygen species have been implicated in pathogenesis of vascular diabetic complications. However, treatment with classic free-radical scavengers and antioxidants has not been yet proved to reduce the risk of developing such complications. In search of more effective treatment we have tested the protective role of Ergothioneine (EGT), in vitro, on C2C12 cells model on FFA-induced lipotoxicity. Cells were incubated for 24 h in the presence of palmitic acid (PA) (250, 500, 750, 1000 mu M), added as pro-oxidant compound, with or without 24-h pre-treatment with EGT. Cells were assessed for cell viability and MAPKs expression by Western Blot. Pre-treatment with EGT resulted in greater cell viability at each PA concentration (EGT 500 mu M: 5, 16, 17, 23% and EGT 1000 mu M: 9, 18, 21 and 25%). In response to PA exposure, p38 and JNK activity increased significantly while EGT prevented such activation. Moreover the analysis of the IL-6 production reveal that EGT is also able to exert anti-inflammatory action inhibiting the PA IL-6 modulation (P < 0.001). In conclusion, these results indicate that 1. EGT has a protective role on PA-induced cell death, possibly via 2. reduced activity of MAPKs cascade having also 3. an anti-inflammatory action exerted on the IL-6 modulation.