Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells

Beatriz Ferrer, Harshini Suresh, Alexey A. Tinkov, Abel Santamaria, João Batista Rocha, Anatoly V. Skalny, Aaron B. Bowman, Michael Aschner

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2098-2115
Number of pages18
JournalMolecular Neurobiology
Volume59
Issue number4
DOIs
StatePublished - Apr 2022

Keywords

  • Ghrelin
  • Heavy metals
  • Methylmercury
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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