Esculin, a Coumarin Glucoside Prevents Fluoride-Induced Oxidative Stress and Cardiotoxicity in Zebrafish Larvae

Fluoride (F^-) is a major groundwater contaminant spread across the world. In excess concentrations, F^- can be detrimental to living beings. F^- exposure is linked to cellular redox dyshomeostasis, leading to oxidative stress-mediated pathologies including heart dysfunction. Due to its potent antioxidant properties, various phytochemicals are found to alleviate the symptoms of F^- toxicity. Hence, we explore the protective effect of esculin (Esc), a coumarin glucoside on F^--induced oxidative stress and cardiotoxicity in zebrafish larvae. The experimental groups consisted of NaF (50 ppm) and Esc (100 μM) groups treated alone and in combination with a control group for 6 h. The groups were maintained till 78 hpf after which the level of oxidants (ROS, LPO, and PCC) and antioxidants (GST, GSH, GPx, SOD, and CAT) were assessed. The results revealed that Esc pretreatment restored the depleted antioxidant markers and reduced the levels of oxidant in the Esc+NaF group, exhibiting its antioxidant potential. In addition, analyses of the heartbeat rate and hemoglobin integrity using o-Dianisidine staining were conducted in the control and experimental groups. Esc treatment prevents F^- induced cardiac changes including tachycardia and altered blood flow. Further, the mRNA expression level of antioxidant genes (nrf2, gstp1, hmox1a, prdx1, and nqo1) and cardiac developmental genes (bmp2b, nkx2.5, myh6, and myl7) confirmed that Esc acts as a potent free radical scavenger and antioxidant defense enhancer, protecting zebrafish larvae from NaF-induced oxidative stress and heart dysfunction.