Hexavalent chromium [Cr(VI)] is an environmental pollutant known for its strong oxidizing and carcinogenic effects. However, its potential to induce ferroptosis in poultry remains poorly understood. This study aims to investigate the induction of ferroptosis by Cr(VI) in DF-1 cells and elucidate the underlying mechanisms. DF-1 cells exposed to Cr(VI) showed increased lipid reactive oxygen species and changes in ferroptosis marker genes (decreased expression of GPX4 and increased expression of COX2). Notably, the addition of the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) can reverse this effect. During the cell death process, Cr(VI) induced ferritinophagy, disrupting iron homeostasis and releasing labile iron ions. We predicted by docking that these iron ions would bind to mitochondrial membrane proteins through virtual docking. This binding was validated through colocalization analysis. In addition, Cr(VI) caused mitophagy, which releases additional ferrous ions. Therefore, Cr(VI) can induce the simultaneous release of ferrous ions through these pathways, thereby exacerbating lipid peroxidation and ultimately triggering ferroptosis in DF-1 cells. This study demonstrates that Cr(VI) can induce ferroptosis in DF-1 cells by disrupting intracellular iron homeostasis and providing valuable insights into the toxic effects of Cr(VI) in poultry and potentially other organisms.

中文翻译：

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Cr(VI) 通过同时扰乱铁蛋白自噬和线粒体自噬的铁稳态来诱导 DF-1 细胞铁死亡

六价铬[Cr(VI)]是一种环境污染物，以其强氧化和致癌作用而闻名。然而，其诱发家禽铁死亡的潜力仍知之甚少。本研究旨在研究 Cr(VI) 在 DF-1 细胞中诱导铁死亡并阐明其潜在机制。暴露于 Cr(VI) 的 DF-1 细胞表现出脂质活性氧增加和铁死亡标记基因的变化（GPX4 表达减少和 COX2 表达增加）。值得注意的是，添加铁死亡特异性抑制剂 Ferrostatin-1 (Fer-1) 可以逆转这种效应。在细胞死亡过程中，Cr(VI) 会诱导铁蛋白自噬，破坏铁稳态并释放不稳定的铁离子。我们通过对接预测这些铁离子将通过虚拟对接与线粒体膜蛋白结合。通过共定位分析验证了这种结合。此外，Cr(VI) 会引起线粒体自噬，从而释放出额外的亚铁离子。因此，Cr(VI)可以通过这些途径诱导亚铁离子同时释放，从而加剧脂质过氧化，最终引发DF-1细胞的铁死亡。这项研究表明，Cr(VI) 可以通过破坏细胞内铁稳态来诱导 DF-1 细胞铁死亡，并为 Cr(VI) 对家禽和其他潜在生物体的毒性作用提供有价值的见解。