Amelioration of Fluoride Induced Toxicity by <i>trans</i> ‐Chalcone in Zebrafish Larvae and Its Gill Cell Line: An In Vivo and In Vitro Approach

Fluoride (F-), a common environmental contaminant resulting from both natural and human activities, poses a threat to animal and human health globally. Plant-derived phytochemicals with pharmacological properties offer promising potential for mitigating various chemical toxicants. In this study, we explored the potential benefits of trans-chalcone (TC) in counteracting sodium fluoride (NaF) induced toxicity in zebrafish models. The cytotoxic effects of NaF (0-5 mM) and TC (0-100 μM) were evaluated in DrG cells using MTT and AB assays. The larvae and DrG cells were treated with NaF alone and in combination with TC to evaluate for ROS generation, biochemical parameters, and the mRNA expression profiles of inflammatory genes (cox-2a, cox-2b, tnf-α, and il-1β) as well as apoptotic regulatory genes (bcl-2, bax, p53, and cas3). Mitochondrial membrane integrity in DrG cells was analyzed using rhodamine 123. Additionally, the cardiac rate and tactile response were measured in zebrafish larvae. Our results demonstrated that TC mitigated the toxic effects of NaF by modulating cellular oxidant levels, preserving mitochondrial membrane integrity, and enhancing antioxidant responses in DrG cells and larvae. Furthermore, TC restored the cardiac rate and tactile response in fluoride-treated larvae and normalized the expression of inflammatory and apoptotic regulatory genes in response to NaF toxicity. Overall, our findings suggest that TC is a promising candidate for reducing cellular oxidant levels, inflammation, and apoptotic stress associated with NaF derived toxicity, utilizing both in vivo and in vitro approaches.