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), ALD (15 mgkg) + RBN (6 mgkg) and RBN (6 mgkg) 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.