Elucidating the Protective Potential of Ferulic Acid Against Sodium Arsenite- Induced Thyroid and Adrenal Toxicity: An Integrated In-Silico Molecular Docking and In-Vivo Experimental Approach.

Arsenic is a hazardous environmental contaminant that adversely affects human and animal health. The present study aimed to investigate the potential adverse effects of sodium arsenite (SA) as an endocrine disruptor on the thyroid and adrenal glands. This study also investigated the endocrine-protective effect of ferulic acid (FA) in male rats exposed to SA. Forty male Wistar rats were organized into four groups: Control, FA (50 mg/kg), SA (10 mg/kg), and SA + FA. All substances were administered orally for 28 days. Our findings demonstrated that SA's ability to exert harmful effects was observed microscopically as vacuolation of colloid and follicular cells, as well as adrenal gland cell necrosis. As well as pronounced positive immunoreactivity for Cyclooxygenase-2 (COX-2). Furthermore, SA significantly declined triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) serum levels. The expression of nuclear factor kappa β (NF-ƙβ), Interleukin-1 beta (IL-1β), and Nibrin (NBN) genes significantly increased. In contrast, nuclear factor erythroid 2-related factor 2 (Nrf-2) and catalase (CAT) antioxidant genes significantly diminished. Additionally, a docking simulation was performed to explain the binding affinity of FA on BCL2-associated X (Bax) and Cytochrome C (CYCS). Molecular docking demonstrated that FA binds strongly to Bax (ΔG = - 6.87 kcal/mol) and cytochrome C (ΔG = - 6.54 kcal/mol), which could imply a role in affecting mitochondrial apoptosis. In contrast, its high affinity for catalase (ΔG = - 6.30 kcal/mol) aligns with its potential antioxidant and cytoprotective mechanisms. Interestingly, FA administration provided partial protection against the toxic effects of sodium arsenite exposure in the examined organs.