Protective effect of Shenfushu granules on nephrotoxicity induced by cisplatin in mice

摘要

Objective To evaluate the impact of Shenfushu granules on cisplatin-induced renal dysfunction and explore the possible mechanisms.Methods Male institute of cancer research(ICR) mice were randomly divided into 4 groups:control group (0.9％ NaC1),Shenfushu group (Shenfushu granules 1 g · kg-1),cisplatin group(0.9％ NaC1 for 9 d and a single dose of cisplatin 20 mg · kg-1 was given by intraperitoneal injection on 7th day),Shenfushu + cisplatin group (Shenfushu granules 1 g · kg-1 gavage for 9 d and a single dose of cisplatin 20 mg · kg-1 was given by intraperitoneal injection on 7th day).Animals were euthanized 72 h following cisplatin dosing.Biochemical parametem including serum creatinine and blood urea nitrogen levels were analyzed by automatic biochemical analyzer.Hematoxylin-eosin (HE) staining was performed inhistopathological examination.The peroxidative product malondialdehyde (MDA) and antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected according to kits.Protein expressions of nuclear factor-E2-related factor 2 (Nrf2),hemeoxygenase 1 (HO-1),quinine oxidoreductase 1 (NQO1),multidrug resistance protein 2 (MRP2) and multidrug and toxic compound extrusion protein 1 (MATE1) were measured in western blot analysis.Platinum contents in kidney were determined with inductively coupled plasma mass spectrometry (ICP-MS) method.Results The serum creatinine in cisplatin group and Shenfushu + cisplatin group were (12.14 ± 4.64),(7.60 ± 3.49) μmol · L-1;blood urea nitrogen were (34.12 ±9.48),(15.92 ±4.33) mmol · L-1;GSH-Px were (78.26 ±7.02),(95.87 ± 14.08) U· mg-1 protein;SOD were (8.85 ±3.99),(12.68 ±3.62) U · mg-1 protein,MDA were (6.96 ±2.25),(4.33 ± 1.50) nmol · mg-1 protein;platinum contents were (12.56 ± 1.30),(9.67 ± 0.97) ng · mg-1 tissue.Western blotting analysis revealed that Shenfushu granules enhanced expressions of Nrf2-mediated antioxidant pathway and efflux transporter in cisplatin-exposed animals.Conclusion Shenfushu granules exhibited renal protective effects on cisplatin-induced renal impairment,possibly associated with its modulating on Nrf2-mediated antioxidant pathway and efflux transporters.

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