Unraveling mercury-selenium interactions through metabolomics: Impacts on riverside communities in the Amazon

Amazonian riverside populations face high mercury (Hg) and selenium (Se) exposure through diet and fish-rich consumption. While Hg is a well-known neurotoxin with systemic effects, the impacts of chronic Se exposure and its interaction with Hg in the human body remain insufficiently understood. Consequently, we aimed to elucidate metabolomic changes associated with varying Hg and Se blood levels. This study analyzed 352 blood samples, categorized into five groups based on Hg and Se levels, using nuclear magnetic resonance (NMR) spectroscopy. Partial least squares discriminant analysis (PLS-DA) revealed that elevated Hg exposure resulted in disrupted glucose, lactate, and branched-chain amino acid metabolism due to oxidative stress and energy dysfunction. Remarkably, individuals with high Hg and elevated Se in blood exhibited metabolic profiles closer to the control group, suggesting a protective Se effect. Additionally, proline and glutamine exhibited differential responses to Hg and Se levels. Furthermore, our analysis provided insights into Hg detoxification mechanisms through selenoprotein interactions. These findings highlight the potential of Se to mitigate Hg toxicity and underscore its dietary importance for at-risk populations.