Nephroprotective potential of robinin to counteract aldicarb induced renal dysfunction via modulating TLR4/MyD88, HMGB1/RAGE, NF-κB pathway: A biochemical and pharmacodynamic approach.

The current investigation was conducted to evaluate the nephroprotective potential of robinin (RBN) to avert aldicarb (ALD) induced renal impairments. Thirty-two adult albino rats (Sprague Dawley) were divided into four groups including control, ALD (15 mgkg-1), ALD (15 mgkg-1) + RBN (6 mgkg-1) and RBN (6 mgkg-1) alone treated group. The results of the current study demonstrated that ALD intoxication increased the gene expression of receptor for advanced glycation end products (RAGE), tumor necrosis factor- α (TNF-α), toll-like receptor 4 (TLR4), high mobility group box1 (HMGB1), nuclear factor-kappa B (NF-κB), myeloid differentiation primary response protein 88 (MyD88), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and interleukin-1β (IL-1β). Moreover, activities of HO-1, GSH, GPx, SOD, GSR, and CAT were suppressed while the levels of ROS and MDA were escalated following the ALD exposure. ALD intoxication upregulated the levels of cystatin C, KIM-1, creatinine, NAG, uric acid, urea, NGAL and BUN while reducing the levels of creatinine clearance in renal tissues. The levels of Bax, Caspase-9 and Caspase-3 were elevated while the levels of Bcl-2 were reduced after ALD administration. Histopathological analysis showed ALD disrupted the normal architecture of renal tissues. However, RBN therapy substantially protected the renal tissues owing to its antioxidative, anti-inflammatory and anti-apoptotic potential.