Mechanism of Liver Injury Induced by Cr6+ in Zebrafish and Protective Effect of Selenomethionine

Hexavalent chromium (Cr⁶⁺) is a potent environmental toxicant known to accumulate in the liver; however, the molecular underpinnings of its hepatotoxicity remain incompletely understood. In this study, we investigated the biochemical mechanisms of Cr⁶⁺-induced liver injury and the protective efficacy of selenomethionine (Se-Met) using a transgenic zebrafish model. We demonstrate that exposure precipitates severe hepatic steatosis and mitochondrial dysfunction, characterized by the dysregulation of lipid metabolism genes and the activation of ferroptosis pathways. Specifically, Cr⁶⁺ toxicity was driven by the depletion of glutathione (GSH) and the suppression of the anti-ferroptotic protein glutathione peroxidase 4 (GPX4). Notably, these pathological alterations were significantly attenuated by both the ferroptosis inhibitor ferrostatin-1 (Fer-1) and low-dose Se-Met. Furthermore, transcriptomic profiling revealed that Se-Met exerts its protective effects primarily by modulating glycerolipid metabolism, thereby mitigating lipid accumulation. Collectively, our findings establish ferroptosis as a critical driver of Cr⁶⁺-induced hepatotoxicity and highlight Se-Met as a promising biochemical intervention to mitigate chromium-associated hepatic damage in aquaculture systems.