Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells

Methylmercury (MeHg) is a global pollutant, which can cause damage to the central nervous system at both high-acute and chronic-low exposures, especially in vulnerable populations, such as children and pregnant women. Nowadays, acute-high poisoning is rare. However, chronic exposure to low MeHg concentrations via fish consumption remains a health concern. Current therapeutic strategies for MeHg poisoning are based on the use of chelators. However, these therapies have limited efficacy. Ghrelin is a gut hormone with an important role in regulating physiologic processes. It has been reported that ghrelin plays a protective role against the toxicity of several xenobiotics. Here, we explored the role of ghrelin as a putative protector against MeHg-induced oxidative stress. Our data show that ghrelin was able to ameliorate MeHg-induced reactive oxygen species (ROS) production in primary neuronal hypothalamic and hippocampal cultures. An analogous effect was observed in mouse hypothalamic neuronal GT 1-7 cells. Using this model, our novel findings show that antioxidant protection of ghrelin against MeHg is mediated by glutathione upregulation and induction of the NRF2/NQO1 pathway.