Antagonistic effects of selenium on methylmercury-induced toxicity through mitochondrial quality control and enhanced GSH synthesis in Caenorhabditis elegans.

Selenium (Se), an essential trace element, plays a critical role in protecting the toxicity of methylmercury (MeHg). However, its detoxification mechanism for alleviating MeHg-induced damage remains largely unexplored. This study focused on the antagonistic effects of Se supplementation on the toxic responses induced by MeHg pretreatment in Caenorhabditis elegans. Our results showed that following a 20 h pre-exposure to MeHg, 4 h exposure to Se effectively and rapidly antagonized the reproductive and neurological impairments induced by MeHg. Meanwhile, we found that the total Hg content decreased from 166 ± 46.0 to 109 ± 18.7 µg/g after the addition of Se. Apart from inhibiting the bioaccumulation of Hg, Se supplementation reduced MeHg-induced reactive oxygen species (ROS) and promoted mitochondrial fusion to improve mitochondrial quality. In addition, MeHg-induced autophagy could be alleviated by increasing lysosome activity after the addition of Se. Further studies revealed that Se supplementation modulated the expression of gss-1 and gst-4, regulating glutathione (GSH) synthesis and elevated MeHg-decreased GSH content from 45.5 % to 79.7 %. These findings suggested that Se recovered MeHg-induced reproductive and neurological damage by modulating mitochondrial function and GSH synthesis, providing valuable insights for developing novel therapeutic strategies against MeHg toxicity.