Selenium represses microRNA-202-5p/MICU1 aixs to attenuate mercuric chloride-induced kidney ferroptosis

Mercuric chloride (HgCl₂) is a nephrotoxic contaminant that is widely present in the environment. Selenium (Se) can effectively antagonize the biological toxicity caused by heavy metals. Here, in vivo and in vitro models of Se antagonism to HgCl₂-induced nephrotoxicity in chickens were established, with the aim of exploring the specific mechanism. Morphological observation and kidney function analysis showed that Se alleviated HgCl₂-induced kidney tissue injury and cytotoxicity. The results showed that ferroptosis was the primary mechanism for the toxicity of HgCl₂, as indicated by iron overload and lipid peroxidation. On the one hand, Se significantly prevented HgCl₂-induced iron overload. On the other hand, Se alleviated the intracellular reactive oxygen species (ROS) levels caused by HgCl₂. Subsequently, we focused on the sources of ROS during HgCl₂-induced ferroptosis. Mechanically, Se reduced ROS overproduction induced by HgCl₂ through mitochondrial calcium uniporter (MCU)/mitochondrial calcium uptake 1 (MICU1)-mediated mitochondrial calcium ion (Ca²⁺) overload. Furthermore, a dual luciferase reporter assay demonstrated that MICU1 was the direct target of miR-202-5p. Overall, Se represses miR-202-5p/MICU1 axis to attenuate HgCl₂-induced kidney ferroptosis.