Butylated hydroxytoluene protects against sodium arsenite-induced hepatorenal toxicities: <i>in vivo</i> and <i>in silico</i> studies

Arsenic is a global environmental contaminant. Sodium arsenite (NaAsO₂), one of the arsenic compounds, is toxic. Prolonged exposure to NaAsO₂ causes various detrimental effects on body organs. Butylated hydroxytoluene (BHT), a synthetic antioxidant may retard the deleterious effects of free-radical-induced damage. We hereby investigated the chemo-protective role of BHT on sodium arsenite-induced hepatorenal toxicity in rats. Rats (n = 49, 110 ± 10 g) were grouped into seven with 7 animals each: groups 1 and 2 served as the negative controls and were administered corn oil and distilled water respectively, group 3 NaAsO₂ (2.5 mg/kg); Group 4 BHT (25 mg/kg); Group 5 BHT (50 mg/kg); Group 6 BHT (25 mg/kg) + NaAsO₂, and Group 7 BHT (50 mg/kg) + NaAsO₂, for 14 days. Liver and kidney functions were assessed based on their specific markers, and inflammation, oxidative stress, and antioxidant profiles were evaluated spectrophotometrically. Molecular docking simulation was employed for <i>in silico</i> studies. Results revealed that NaAsO₂ caused a notable increase in the serum activities of AST, ALT, ALP, urea and creatinine levels. Furthermore, there was a significantly increased oxidative stress and inflammatory markers with a concomitant decrease in antioxidant markers in the group exposed to NaAsO₂ alone. Conversely, there were reversals of these effects in the groups co-exposed to NaAsO₂ and BHT. Molecular docking revealed that BHT exhibited a high binding affinity for cyclooxygenase (COX) and interacted with critical amino acids in the active site of the enzymes.