Glyphosate induces toxicity and modulates calcium and NO signaling in zebrafish embryos

Glyphosate, an herbicide used worldwide, has emerged as a pollutant. However, its toxic effects are debated by regulatory authorities. Therefore, it is essential to keep the use of such chemicals under continuous observation, and their effects must be re-evaluated. We used zebrafish embryos to evaluate the toxic effects of glyphosate and its mechanisms. We found that glyphosate induced significant toxicity in a time and concentration-dependent manner. We observed an LD₅₀ of 66.04 ± 4.6 μg/mL after 48 h of exposure. Glyphosate significantly reduced the heartbeat in a time and concentration-dependent manner indicating cardiotoxicity. Selective downregulation of Cacana1C (L-type calcium channel) and ryr2a (Ryanodine receptor) genes along with selective upregulation of hspb11 (heat shock protein) gene was observed upon exposure to glyphosate indicating alterations in the calcium signaling. A reduction in the nitric oxide (NO) generation was also observed in the zebrafish embryos upon exposure to glyphosate. Our results indicate that glyphosate induces significant toxicity including cardiotoxicity in zebrafish embryos in a time and concentration-dependent manner. Further, cardiotoxicity may be due to changes in calcium and NO signaling.