Unraveling 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 endocrine disruptions after 28 days of oral administration.Male Wistar rats were divided into a control (CR) and three treatment groups, receiving IM (45 mg/kg), CL (300 mg/kg), and an admixture of IM and CL.The gathered findings indicate that IM and CL induced spuriously abnormal thyroid hormone measurements distinguished by a decrement in circulating levels of T3, T4, with a normal/slight increase in TSH concentration. Equally, a sharp decline in insulin levels was recorded in the IM (0.46 ± 0.33 pmol/L) and CL (2.08 ± 0.43 Pmol/L) groups compared to the healthy specimens (8.21 ± 0.014 Pmol/L). Additionally, high plasma alanine transferase (ALT/SGPT) and aspartate transferase (AST/SGOT) levels, as well as alkaline phosphatase (Alk-P) and metabolite concentrations, including serum creatinine (SCR), uric acid (SUA), and urea levels, were recorded in all treated groups. Both IM and CL significantly compromised the antioxidant defense system by increasing the MDA level, decreasing the GSH content, and inhibiting the activity of CAT and SOD.We systematically investigated the binding affinity and the potential inhibitory effects of IM and CL on a series of enzymes integral to the blood transport and receptor binding of THs, such as MCT8 and TSHR. A significant binding affinity of IM and CL to these proteins was observed, suggesting the possibility of competitive or allosteric inhibition. 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 this result supply beneficial knowledge for future therapeutic endeavors.