BackgroudDrinking water contamination with hexavalent chromium [Cr (VI)] has become one of the most serious public health problems, thus the investigation of Cr (VI)-induced hepatotoxicity has attracted much attention in recent years.MethodsIn the present study, by determining the indices of hepatotoxicity induced by Cr (VI), the source of accumulated reactive oxygen species (ROS), and the protective effect of the antioxidant Vitamin C (Vit C), we explored the mechanisms involved in Cr (VI)-induced hepatotoxicity in vitro and in vivo.ResultsWe found Cr (VI) caused hepatotoxicity characterized by the alterations of several enzymatic and cytokine markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukine-1β (IL-1β), and tumor necrosis factor-α (TNF-α), etc. ROS production after Cr (VI) exposure was origins from the inhibition of electron transfer chain (ETC) and antioxidant system. Vit C inhibited ROS accumulation thus protected against Cr (VI)-induced hepatotoxicity in L-02 hepatocytes and in the rat model.ConclusionsWe concluded that ROS played a role in Cr (VI)-induced hepatotoxicity and Vit C exhibited protective effect. Our current data provides important clues for studying the mechanisms involved in Cr (VI)-induced liver injury, and may be of great help to develop therapeutic strategies for prevention and treatment of liver diseases involving ROS accumulation for occupational exposure population.

Hexavalent chromium [Cr(VI)] has aroused the main interest of environmental health researchers due to its high toxicity. Liver is the main target organ of Cr(VI), and the purpose of this study was to explore whether mitophagy contributes to Cr(VI)-induced hepatotoxicity and to demonstrate the potential mechanisms. Cr(VI) exposure induced mitochondrial loss, energy metabolism disorders and cell apoptosis, which were associated with the occurrence of excessive mitophagy characterized by the increased number of green fluorescent protein-microtubule-associated protein light chain 3 (GFP-LC3) puncta and lysosomal colocalization with mitochondria. In addition, the suppression of mitophagy by autophagy-related 5 (ATG5) siRNA can effectively inhibit Cr(VI)-induced mitochondrial loss and cytotoxicity. In summary, we reached the conclusion that Cr(VI)-induced overactive mitophagy contributes to mitochondrial loss and cytotoxicity in L02 hepatocytes, which will further reveal the possible mechanisms of Cr(VI)-induced hepatotoxicity, and provide a new experimental basis for the study of the health hazard effects of chromium.