Long-Term Impact of Cr(VI) Exposure in Swiss Albino Mice: ROS-Driven Modulation of Autophagy and Cellular Fate.

Abstract

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.