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

Abstract

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 microM), 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 microM: 5, 16, 17, 23% and EGT 1000 microM: 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.

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

“…Moreover, evidence suggests that that tissues may increase ET uptake (by elevating expression of its transporter, OCTN1) in response to disease or tissue injury, to possibly mitigate further oxidative damage [26,64]. In addition to alleviating Ab oligomer-mediated toxicity as demonstrated in this study, ET has also been demonstrated to function as an antioxidant [23,24], chelate metal ions [58,60], modulate inflammation [65,66], accumulate in mitochondria and protect against mitochondrial dysfunction [67,68] and prevent NMDA excitotoxicity-induced neuronal death in rat retinal neurons [29]. These are all known to be pathological features of AD.…”

Ergothioneine as an Anti-Oxidative/Anti-Inflammatory Component in Several Edible Mushrooms

“…Cell viability remained at > 90% after all of the above treatments, as assessed by MTT assay (data not shown). Recently, Laurenza et al (2008) used a C2C12 cell model on free fatty acid-induced lipotoxicity to examine the protective role of EGT, and found that EGT was able to exert anti-inflammatory effects by inhibiting IL-6 modulation. We found that l-EGT suppressed TNF-α-induced IL-6 release in adipocytes.…”

Plasma L-Ergothioneine Measurement by High-Performance Liquid Chromatography and Capillary Electrophoresis after a Pre-Column Derivatization with 5-Iodoacetamidofluorescein (5-IAF) and Fluorescence Detection

“…In mammals ERT is acquired exclusively through dietary means and accumulated in cells and tissues normally exposed to oxidative stress and involved in inflammatory response [2]. The physiological functions so far suggested for ERT span a wide range and include antioxidant and scavenging activities [3], protection against ischemia/reperfusion-induced injury [4], regulation of metalloenzymes [5], inhibition of DNA oxidation by peroxynitrite (ONOO − ) in the human neuronal hybridoma cell line [3], catalysis of carboxylation or decarboxylation reactions [6], neuroprotection against NMDA excitotoxicity in rats, transport of cations or carbon dioxide [7], neuroprotection against cisplatin toxicity in mice [8], and mediation of thyroid or anticholinergic action [6]. ERT also chelates redox-active bivalent cations such as copper and zinc [9], [10], prevents the pro-oxidant effects of copper [11], and shows radioprotective activity even at low concentrations [12].…”