Developmental, hepatic, and neurotoxicity of dinotefuran and ameliorative effects of Rosmarinus officinalis.

Dinotefuran (DINO) is a chiral neonicotinoid insecticide valued for its efficacy but increasingly scrutinized for health risks. This study evaluated the developmental, neurotoxic, and hepatotoxic effects of DINO in pregnant rats and their fetuses using in vivo and in silico approaches, alongside the ameliorative role of Rosmarinus officinalis extract (RE). Oral administration of DINO at 73.5 and 230 mg/kg during organogenesis caused fetal growth retardation and skeletal abnormalities, indicating developmental toxicity. Biochemical assays revealed oxidative stress in placental, hepatic, and brain tissues, while histology showed structural damage in placenta and fetal liver and brain. Immunohistochemistry demonstrated reduced proliferating cell nuclear antigen (PCNA) expression in placenta and elevated caspase-3 in fetal liver and brain, reflecting impaired proliferation and apoptosis. Ultrastructural examination of fetal liver and cerebral cortex confirmed cellular damage. Molecular docking supported these findings, showing interactions between DINO and antioxidant enzymes-including SOD1, SOD2, SOD3, GPx1, CAT, GS, and GCLC-as well as PCNA and caspase-3. Importantly, co-administration of RE (220 mg/kg) attenuated these toxic effects, highlighting its properties. In conclusion, DINO poses risks to fetal development and organ integrity, whereas RE shows promising potential as an agent against pesticide-induced toxicity during pregnancy, especially in regions with high pesticide exposure.