Unravelling the toxic potential of imidacloprid and chlorothalonil in thyroid, liver, and kidney of rats: a combined experimental and computational investigations

This investigation was planned to evaluate the mechanistic interactions of Imidacloprid (IM) and Chlorothalonil (CL), inducing toxicity after 28 days of oral administration. Male <i>Wistar</i> rats were divided into a control (CR) and three treatment groups, receiving IM (45 mg/kg), CL (300 mg/kg), and mixture of IM+CL.IM and CL,individually or in combination induced a hypothyroidstate with a sharp decline in insulin levels. Additionally, high plasma alanine transferase (ALT/SGPT) and aspartate transferase (AST/SGOT) levels, as well as alkaline phosphatase (Alk-P) and creatinine were recorded in all treated groups. Both IM and CL significantly compromised the antioxidant defense system by increasing the MDA level, and inhibiting the activity of CAT and SOD.A significant binding affinity of IM and CL to enzymes integral to the blood transport and receptor binding of THs like MCT8 and TSHR was observed. The MD simulations revealed the strong and stable interactions between IM, CL, MCT8, and TSH-R. MMGBSA energies showed that both pesticides compete with hormones at active sites, indicating their potential to modulate key enzymes involved in thyroid hormone transport and action.Therefore, it is anticipated that these resultswill provide beneficial knowledge for future therapeutic endeavors.