Prolonged Low-Dose Chromium (VI) Exposure Induces Oxidative Stress, Apoptotic Genes and Epigenetic Modification of DNA Repair Genes in the Brain and Kidney of Swiss Albino Mice.

Abstract

Hexavalent chromium (Cr (VI)) poses a major health risk due to its high solubility and cell permeability, often exceeding permitted drinking water limits globally. Research has highlighted a strong correlation between Cr (VI) exposure through drinking water and increased cancer rates, particularly in near chrome industries. Our previous research demonstrated that chronic low-dose Cr (VI) exposure (2, 5 and 10 ppm) via drinking water stimulated hepatotoxicity in Swiss albino mice. In this study, we investigated the effects of the same doses over 4 and 8 months on the brain and kidney tissues of Swiss albino mice. It was found that oxidative stress markers, including catalase activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, were significantly elevated in both the tissues post-treatment. Prolonged exposure to Cr (VI) led to DNA fragmentation and a reduced organo-somatic index in the affected tissues. Additionally, histoarchitectural alterations were observed in the brain and kidney. Apoptotic gene expression was significantly upregulated after 8 months of exposure, confirmed by immunohistochemical studies indicating apoptosis. DNA repair genes (Rad51, Mutyh, Ogg1, and Mlh1) and genes coding enzymes regulating epigenetics (Sirt1, Dnmt1, Kdm1a, and Ezh2) showed significantly varied expression patterns compared to control. Methylation-specific PCR revealed DNA hypermethylation as a factor in the transcriptional reduction of specific DNA repair genes in these tissues. This study denotes that long-term low-dose Cr (VI) exposure not only surges oxidative stress and changes histoarchitecture and gene expression but also results in epigenetic modifications via DNA hypermethylation, impacting organs like the brain and kidney.