Prenatal exposure to the fungicide flutolanil induces developmental and hepatic toxicity in pregnant rats and their fetuses: Insights from In Vivo and In Silico studies and the protective role of Chlorella vulgaris.

Flutolanil (FLTN), a widely used succinate dehydrogenase-inhibiting fungicide, has raised concerns regarding potential health risks. This study examined the effects of the commercial formulation of FLTN (FLTN-CF) on pregnant rats and their fetuses during organogenesis, as well as the potential protective effects of Chlorella vulgaris (C. vulgaris). Maternal exposure to FLTN-CF (170 and 510 mg/kg) increased fetal resorptions, growth retardation, skeletal malformations, and morphological anomalies. Histopathological examination of maternal and fetal livers revealed pronounced damage. FLTN-CF also induced oxidative stress, evidenced by elevated malondialdehyde levels and reductions in glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Flow cytometry confirmed that FLTN-CF caused G1-phase arrest in maternal and fetal liver cells. Molecular docking supported these findings, showing interactions between FLTN and key antioxidant enzymes (SOD1, SOD2, SOD3, GPx1, CAT, GS, and GCLC) as well as regulators of G1 cell cycle arrest (CDK2, Cyclin E1, CDK4, CDK6, and Cyclin D1). Pre-treatment with C. vulgaris (500 mg/kg) ameliorated FLTN-induced toxicity, restoring antioxidant balance, reducing developmental and hepatic damage, and alleviating cell cycle disruptions. Notably, fetuses were more vulnerable to FLTN-CF toxicity than their mothers. Overall, these results suggest that low-dose C. vulgaris may provide a protective dietary strategy against pesticide-induced toxicity during pregnancy, particularly in regions with high pesticide exposure.