Liver ergothioneine accumulation in a guinea pig model of non-alcoholic fatty liver disease. A possible mechanism of defence?

ABSTRACTL-ergothioneine (ET), a putative antioxidant compound acquired by animals through dietary sources, has been suggested to accumulate in certain cells and tissues in the body that are predisposed to high oxidative stress. In the present study, we identified an elevation of ET in the liver of a guinea pig model of non-alcoholic fatty liver disease (NAFLD), elucidated a possible mechanism for the increased uptake and investigated the possible role for this accumulation. This increase in liver ET levels correlated with cholesterol accumulation and disease severity. We identified an increase in the transcriptional factor, RUNX1, which has been shown to upregulate the expression of the ET-specific transporter OCTN1, and could consequently lead to the observable elevation in ET. An increase was also seen in heat shock protein 70 (HSP70) which seemingly corresponds to ET elevation. No significant increase was observed in oxidative damage markers, F2-isoprostanes, and protein carbonyls, which could possibly...