Objectives: Icariin (ICA) is a bioactive flavonoid with renal protective actions. This study investigated the effects of ICA on renal injury, inflammation, oxidative damage, apoptosis, and survival in a mouse model of cecal ligation and perforation (CLP)-induced sepsis. Methods: Sepsis was induced by CLP. Mice were treated with ICA (30 or 60 mg/kg) for 3 days before CLP. Renal functions, inflammatory responses, oxidative damage, histological changes, apoptosis, and vascular permeability were examined. The effects of ICA on CLP-induced expression of renal nuclear factor-κB (NF-κB), cleaved caspase-3, Bax, and Bcl-2 were evaluated. Results: Mice in the CLP group had a low survival rate and increases in blood urea nitrogen and creatinine levels, proinflammatory cytokine levels, oxidative damage, apoptosis, and vascular permeability. These renal changes were dramatically improved by ICA treatment, especially in the 60 mg/kg ICA group. The detection of molecules involved in the inflammation and apoptosis of the kidney indicated that ICA reduced expression of NF-κB, cleaved caspase-3, and Bax but enhanced expression of Bcl-2. Conclusion: ICA improves CLP-induced mortality and acute kidney injury by inhibiting renal oxidant damage, inflammatory responses, apoptosis, and vascular permeability.

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