Nephroprotective Potential of Tectorigenin Against Thiamethoxam Instigated Renal Toxicity Via Regulating HMGB1/RAGE, TLR4/MyD88, and NF‐κB Pathway in Sprague Dawley Rats: An In‐Vivo and In‐Silico Investigation

ABSTRACT Thiamethoxam (TMX) is a systemic neonicotinoid insecticidal agent that has been reported to damage different organs including the kidneys. Tectorigenin (TRG) is a novel isoflavone that exhibits substantial pharmacological properties. The present research trial was conducted to elucidate the nephroprotective potential of TRG to avert TMX induced renal impairments. Thirty‐six male albino rats ( n = 36) were categorized into following groups i.e., control, TMX (31.26 mg kg −1 ), TMX (31.26 mg kg −1 ) + TRG (25 mg kg −1 ), and TRG (25 mg kg −1 ) treated group. Our results showed that TMX intoxication increased the expression of interleukin‐6 (IL‐6), Receptor for Advanced Glycation End‐products (RAGE), Toll‐like receptor 4 (TLR4), tumor necrosis factor‐alpha (TNF‐α), High‐Mobility Group Box 1 (HMGB1), Cyclooxygenase‐2 (COX‐2), Myeloid Differentiation Primary Response Gene 88 (MyD88), nuclear homoeotic factor beta (NF‐κB), and interleukin‐1 beta (IL‐1β). The enzymatic activities of heme‐oxygenase‐1 (HO‐1), glutathione S‐transferase (GST), catalase (CAT), glutathione reductase (GSR), glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were promoted while the concentration of MDA and ROS in renal tissues. Besides, TMX induces severe alterations in renal health profile as indicated by high concentrations of cystatin C (Cys C), NGAL, creatinine, serum uric acid, KIM‐1, BUN coupled with suppressed levels of creatinine clearance. The levels of Bax, Caspase‐3, and Caspase‐9 were found to be elevated while the levels of Bcl‐2 were reduced following the TMX exposure. Furthermore, TMX exposure disrupted renal morphology, including tubular necrosis, glomerular atrophy, interstitial inflammation, and epithelial desquamation. However, TRG therapy restored renal impairments via regulating antioxidative, anti‐apoptotic, anti‐inflammatory, and histo‐architecture. Our findings were strongly supported by in‐silico findings that demonstrated the potential binding of TRG with key regulatory genes.