Butylated hydroxytoluene protects against sodium arsenite-induced hepatorenal toxicities: in vivo and in silico 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 in silico 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.