Tang Hongge, Li Kunyang, Lin Lin, Wang Wenying, Jian Wenjie
Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen, Fujian, China.
Xiamen Haicang Hospital, Xiamen, Fujian, China.
Front Mol Biosci. 2024 Jul 5;11:1372783. doi: 10.3389/fmolb.2024.1372783. eCollection 2024.
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.
六价铬[Cr(VI)]已被确认为一种人类致癌物和环境污染物，能够影响人体的多个系统。然而，Cr(VI)影响人类神经系统的具体机制仍不清楚。在证实Cr(VI)对大鼠星形胶质细胞有毒性作用后，本研究探讨了不同剂量Cr(VI)暴露下大鼠星形胶质细胞的代谢产物及相关代谢途径。使用CCK8法评估细胞活力，使用DCFH-DA荧光探针测量细胞内活性氧(ROS)水平，通过酶联免疫吸附测定法测定细胞内8-羟基脱氧鸟苷(8-OHdG)含量，使用JC-1探针观察线粒体膜电位，并通过非靶向代谢组学分析鉴定关键代谢产物。随着Cr(VI)剂量的增加，在4、8和16mg/L剂量组中观察到细胞活力显著下降(P<0.05)。在2和4mg/L剂量组中观察到ROS和8-OHdG水平升高、半胱天冬酶-3活性增加以及线粒体膜电位显著降低(P<0.05)。非靶向代谢组学分析揭示了Cr(VI)对鞘氨醇和蛋氨酸等关键代谢产物的影响。KEGG通路富集分析突出了鞘脂代谢和蛋氨酸-半胱氨酸循环在Cr(VI)对大鼠星形胶质细胞作用中的关键作用。我们的研究强调了环境和职业接触Cr(VI)相关的潜在神经健康风险，并为研究神经毒性机制提供了新的视角和方向。
