Cytotoxic activity of pyrimethanil on human testicular teratocarcinoma NT2/D1 cells

Fungicides are widely used in the agricultural sector to ensure a safer and larger crop yields. Nevertheless, they represent potentially harmful agents for the environment and living organisms. Pyrimethanil is a new generation of anilinopyrimidine fungicides used to control both pre- and post-harvest crop diseases. The increasing use of fungicides and their potential biological accumulation in the environment prompt the assessment of their toxicity to non-target organisms, thereby evaluating their hazards and the risk of toxic effects on the environment and humans. Since the toxic effects of pyrimethanil are not fully elucidated, our study aimed to evaluate its toxic potential by testing cytotoxicity, oxidative stress, and apoptosis in the human testicular teratocarcinoma NT2/D1 cell line. Our results showed a dose-dependent reduction in cell number accompanied by significant morphological changes characteristic of apoptotic events. Further, pyrimethanil treatment resulted in an increase in the production of reactive oxygen species in NT2/D1 cells and induced apoptosis, leading to cell death. Additionally, we detected increased expression of two well-known hallmarks of apoptosis, p53 and cleaved Caspase-3. To gain a deeper understanding of the effects of fungicides on human health and the environment, it is important to understand the mechanism of toxicity. The presented results suggest that the fungicide pyrimethanil has a strong cytotoxic effect on cells in vitro, exerts oxidative stress-promoted action and induces apoptosis. Further studies are needed to clarify the molecular mechanisms and assess the overall relationship between the benefits and potential harms of pyrimethanil on human health, particularly reproductive health, as well as on the environment.