Afzelechin alleviates deltamethrin induced hepatic dysfunction via regulating TLR4/MyD88, HMGB1/RAGE and NF-κB pathway

Deltamethrin (DMN) is a type-II pyrethroid that has been documented to instigate numerous organ toxicities. Afzelechin (ALN) is a plant based polyphenolic compound that exhibits marvelous biological properties. The present research was conducted to assess the alleviative potential of ALN against DMN induced hepatic dysregulations. Thirty-six male albino (Sprague Dawley) rats were apportioned into four random groups including the control, DMN (5mgkg⁻¹), DMN (5mgkg⁻¹) + ALN (2mgkg⁻¹), and ALN (2mgkg⁻¹) alone administrated group. ALN protected hepatic tissues against DMN induced oxidative stress, inflammation and apoptosis. ALN supplementation donwregulated the gene expression of receptor for advanced glycation end products (RAGE), high mobility group box1 (HMGB1), tumor necrosis factor- α (TNF-α), Myeloid differentiation primary response 88 (MyD88), nuclear factor- kappa B (NF-κB), interleukin-6 (IL-6), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), and interleukin-1β (IL-1β). Besides, ALN administration reduced the levels of reactive oxygen species (ROS) and malondialdehyde while increasing the activities of glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH). The levels of hepatic function markers including GGT, ALT, ALP, and AST were lowered while the concentrations of albumin and total proteins were promoted following the ALN treatment. The levels of Bax, Caspase-9 and Caspase-3 were suppressed while the levels of Bcl-2 were escalated after ALN therapy. Moreover, ALN treatment remarkably mitigated DMN induced histological impairments. These findings highlight the hepatoprotective efficacy of ALN against DMN induced liver toxicity.