Islam Shehnaz, Sarkar Olivia, Mukherjee Sunanda, Chattopadhyay Ansuman
Department of Zoology, Visva-Bharati, Santiniketan, 731235, West Bengal, India.
Biol Trace Elem Res. 2025 Apr 3. doi: 10.1007/s12011-025-04599-w.
Hexavalent chromium [Cr(VI)], due to its high solubility and permeability, is significantly more toxic than trivalent chromium [Cr(III)] as it generates reactive oxygen species (ROS) during cellular reduction. Industrial discharges have led to increasing Cr(VI) contamination in surface and groundwater, posing serious environmental and public health concerns. In our previous study, we demonstrated that exposure to 5 ppm Cr(VI) for 4 and 8 months adversely affected body weight, water consumption, and liver function in Swiss albino mice. Histological analyses revealed tissue alterations, disrupted DNA repair gene expression in liver tissue, and a marked increase in apoptotic gene expression after 8 months of exposure. Building on these findings, we employed the same Cr(VI) concentration (5 ppm via drinking water) over 4 and 8 months in the present study. Our results showed a significant increase in ROS generation in the liver, brain, and kidney tissues at both time intervals. Additionally, the presence of autophagolysosomes was markedly elevated after chronic Cr(VI) exposure in each tissue. We also observed altered expression patterns of key autophagy-related genes (Atg5, Beclin1, and Lc3) and mTor in these tissues. Immunohistochemical analysis further confirmed a significant increase in LC3B expression after 4 months of exposure. Our findings suggest that heightened intracellular oxidative stress triggers a protective autophagy response, mediated via mTOR signaling, to maintain cellular integrity. However, prolonged toxic insult and ROS accumulation may eventually shift pro-survival autophagy toward apoptotic cell death in the liver and brain tissues.
六价铬[Cr(VI)]因其高溶解性和渗透性，比三价铬[Cr(III)]的毒性大得多，因为它在细胞还原过程中会产生活性氧(ROS)。工业排放导致地表水和地下水中的Cr(VI)污染不断增加，引发了严重的环境和公共卫生问题。在我们之前的研究中，我们证明，瑞士白化小鼠暴露于5 ppm的Cr(VI)中4个月和8个月会对体重、饮水量和肝功能产生不利影响。组织学分析显示组织发生改变，肝组织中DNA修复基因表达受到破坏，暴露8个月后凋亡基因表达显著增加。基于这些发现，在本研究中，我们在4个月和8个月的时间里采用了相同的Cr(VI)浓度(通过饮用水摄入5 ppm)。我们的结果表明，在这两个时间间隔内，肝脏、大脑和肾脏组织中的ROS生成均显著增加。此外，在每个组织中，慢性Cr(VI)暴露后自噬溶酶体的数量明显增加。我们还观察到这些组织中关键自噬相关基因(Atg5、Beclin1和Lc3)和mTor的表达模式发生了改变。免疫组织化学分析进一步证实，暴露4个月后LC3B的表达显著增加。我们的研究结果表明，细胞内氧化应激增强会触发一种保护性自噬反应，通过mTOR信号传导介导，以维持细胞完整性。然而，长期的毒性损伤和ROS积累最终可能会使肝脏和脑组织中促生存的自噬转变为凋亡性细胞死亡。
