The Protective Effects of Sika Deer Antler Protein on Cisplatin-Induced Nephrotoxicity

Abstract

Background/Aims: This study measured the effect of Sika deer (Cervus nippon Temminck) antler protein (SDAPR), glycoproteins (SDAG), and polysaccharides (SDAPO) on cisplatin-induced cytotoxicity in HEK 293 cells, and investigated the effect of SDAPR against cisplatin-induced nephrotoxicity in mice. Methods: Cell viability was measured by MTT assay. ICR mice were randomly divided into five groups: control, cisplatin with vehicle, and cisplatin with SDAPR at three concentrations: 5, 10, or 20 mg/kg, p.o., 10 d. Cisplatin was injected on 7th day (25 mg/kg, i.p.). Renal function, oxidative stress, levels of inflammatory factors, and expression of apoptosis-related proteins were measured in vivo. Renal tissues were stained with TUNEL and H&E to observe renal cell apoptosis and pathological changes. Results: Pretreatment with SDAPR (125-2000 µg/mL) significantly improved cell viability, with an EC50 of approximately 1000 µg/mL. SDAPR also ameliorated cisplatin-induced histopatholo- gic changes, and decreased blood urea nitrogen (BUN) and creatinine (Cr) (P < 0.05). Western blotting analysis showed SDAPR clearly decreased expression levels of cleaved-caspase-3 and Bax, and increased the expression level of Bcl-2 (P < 0.01). Additionally, SDAPR markedly regulated oxidative stress markers and inflammatory cytokines (P<0.05). TUNEL staining showed decreased apoptosis after SDAPR treatment (P < 0.01). Conclusions: These results indicate that SDAPR can be an effective dietary supplement, to relieve cisplatin-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vivo.

Keywords

• Oxidative stress
• Apoptosis
• Inflammation
• Renal protection