Morin ameliorates lipopolysaccharide-induced acute kidney injury in rats via alteration of TLR4/NF-κB, COX-2/PGE2, and monocyte chemoattractant protein-1/CXCL1 signaling pathway

Abstract: BACKGROUND: Acute kidney injury (AKI), a quick decline of renal function occurring over hours to days, is defined biochemically as defective filtration, abnormal retention of nitrogenous waste in the blood, and disturbances of replacement metabolism in electrolytes and water. In this study, we examined the renal protective effect of morin on lipopolysaccharide (LPS)-induced AKI in the rats and manifested the mechanism involved. MATERIALS AND METHODS: Intraperitoneal administration of LPS (10 mg/kg) was used for the induction of AKI in the rats, and the rats received the oral administration of morin (5, 10, and 15 mg/kg). The body weight, renal weight, and renal index were estimated. Renal parameters, soluble receptor for advanced glycation end products (sRAGE), advanced glycation end products (AGEs), antioxidant parameter, indoxyl sulfate, inflammatory cytokines, and inflammatory parameters were estimated. The mRNA expressions were also estimated. RESULTS: Morin treatment improved the body weight and reduced the renal weight and renal index. Morin treatment altered the level of renal parameters (creatinine, blood urea nitrogen [BUN], and albumin); sRAGE, AGEs, antioxidant parameters (catalase [CAT], superoxide dismutase [SOD], malonaldehyde, glutathione [GSH], oxidized GSH; indoxyl sulfate [urine, serum, and renal tissue]); inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin (IL)-1α, IL-1 β, IL-2, IL-4, IL-5, IL-7, IL-10, IL-17, C-X-C motif chemokine ligand 1 (CXCL1), interferon γ, monocyte chemoattractant protein-1 (MCP-1), MCP-1α (MCP-1α), MIP-2, granulocyte macrophage colony-stimulating factor); inflammatory parameters (cyclooxygenase-2 [COX-2], prostaglandin E 2 [PGE2], inducible nitric oxide synthase, transforming growth factor-β, and nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB]), respectively. Morin treatment altered the mRNA expression of kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL), manganese SOD, TNF-α, IL-1 β, IL-6, CAT, MCP-1, NADPH Oxidase 4 (NOX4), and toll-like receptor 4 (TLR4). CONCLUSION: The result clearly showed the renal protective effect of morin against LPS induced AKI via alteration of TLR4/NF-κB, COX-2/PGE2, and MCP-1/CXCL1 signaling pathways.