Study on the metabolic effects of hexavalent chromium [Cr (VI)] on rat astrocytes using un-targeted metabolomics.

Hexavalent chromium [Cr (VI)] has been identified as a human carcinogen and environmental pollutant capable of affecting multiple systems in the human body. However, the specific mechanisms by which Cr (VI) affects the human nervous system remain unclear. Following confirmation of Cr (VI)'s toxic effects on rat astrocytes, this study explores the metabolites and associated metabolic pathways of rat astrocytes under different doses of Cr (VI) exposure. Cell viability was assessed using CCK8 assays, intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescent probes, intracellular 8-hydroxydeoxyguanosine (8-OHdG) content was determined by Elisa, mitochondrial membrane potential was observed using JC-1 probes, and key metabolites were identified through untargeted metabolomics analysis. With increasing Cr (VI) doses, significant decreases in cell viability were observed in the 4, 8, and 16 mg/L dose groups ( < 0.05). Elevated levels of ROS and 8-OHdG, increased caspase-3 activity, and significant reductions in mitochondrial membrane potential were observed in the 2 and 4 mg/L dose groups ( < 0.05). Untargeted metabolomics analysis revealed Cr (VI)'s impact on key metabolites such as sphingosine and methionine. Enrichment analysis of KEGG pathways highlighted the critical roles of sphingolipid metabolism and the methionine-cysteine cycle in the effects of Cr (VI) on rat astrocytes. Our study underscores the potential neuro-health risks associated with environmental and occupational exposure to Cr (VI) and provides new perspectives and directions for investigating neurotoxic mechanisms.