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

## TL;DR

This study shows that Cr6+ causes liver damage in zebrafish through a process called ferroptosis, and selenomethionine can protect against this damage.

## Contribution

The study identifies ferroptosis as a key mechanism of Cr6+ toxicity and demonstrates the protective role of selenomethionine in zebrafish.

## Key findings

- Cr6+ exposure causes liver damage through ferroptosis, linked to GPX4 suppression and GSH depletion.
- Selenomethionine protects the liver by regulating lipid metabolism and reducing ferroptosis.
- Low-dose selenomethionine is effective in mitigating Cr6+-induced hepatic defects in zebrafish.

## Abstract

Hexavalent chromium (Cr6+) is a highly toxic environmental pollutant and a Group 1 carcinogen that accumulates in the liver via the food chain, posing significant health risks. In this study, we utilized liver-transgenic zebrafish to investigate the mechanisms of Cr6+-induced liver damage and evaluated the protective potential of selenomethionine (Se-Met). We discovered that Cr6+ exposure leads to hepatic steatosis (fatty liver) and mitochondrial dysfunction by triggering “ferroptosis”—a specific type of cell death linked to iron accumulation and lipid peroxidation. This toxicity was driven by the suppression of the protective protein GPX4 and the depletion of glutathione (GSH). Crucially, both a specific ferroptosis inhibitor (Fer-1) and low-dose Se-Met effectively alleviated these defects. Further analysis revealed that Se-Met exerts its protection by regulating lipid metabolism pathways. In conclusion, our findings identify ferroptosis as a key driver of chromium toxicity and suggest that Se-Met could serve as a safe, effective feed additive in aquaculture to mitigate the risks of environmental heavy metal contamination.

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.