Abstract
Highlights
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- Almost 200 million people all over the world are facing dreadful effects of fluoride.
- Mice were treated orally with environmentally relevant concentration of fluoride for 8 months.
- Fluoride treatment resulted into histopathology, oxidative stress response and transcriptional alterations of Ogg1 and Rad51.
- DNA fragmentations and apoptosis induction was observed in liver and brain.
- Fluoride induced down-regulation of Rad51 due to promoter hypermethylation is first time reported in this study.
Chronic exposure to fluoride (F) beyond the permissible limit (1.5 ppm) is known to cause detrimental health effects by induction of oxidative stress-mediated DNA damage overpowering the DNA repair machinery. In the present study, we assessed F induced oxidative stress through monitoring biochemical parameters and looked into the effect of chronic F exposure on two crucial DNA repair genes Ogg1 and Rad51 having important role against ROS induced DNA damages. To address this issue, we exposed Swiss albino mice to an environmentally relevant concentration of fluoride (15 ppm NaF) for 8 months. Results revealed histoarchitectural damages in liver, brain, kidney and spleen. Depletion of GSH, increase in lipid peroxidation and catalase activity in liver and brain confirmed the generation of oxidative stress. qRT-PCR result showed that expressions of Ogg1 and Rad51 were altered after F exposure in the affected organs. Promoter hypermethylation was associated with the downregulation of Rad51. F-induced DNA damage and the compromised DNA repair machinery triggered intrinsic pathway of apoptosis in liver and brain. The present study indicates the possible association of epigenetic regulation with F induced neurotoxicity.
