Salvianolic Acid a Ameliorates Cisplatin-Induced Nephrotoxicity in Mice

Cisplatin (DDP) was widely used for solid tumor chemotherapy. Unfortunately, nephrotoxicity is a frequent devastating adverse effect of DDP. Salvianolic acid A (SAA), a Chinese drug metamer, had protection effect against chronic kidney injury. However, the effect of SAA on nephrotoxicity that induced by DDP remains unclear. In this study, we investigated the effect of SAA on nephrotoxicity that induced by DDP. In addition, the underlying mechanism in this effect has been also explored. In this experiment, SAA was administered by oral gavage at doses of 17.6 mg/kg for 4 weeks after intraperitoneal DDP 20 mg/kg injection. The detection of serum creatinine, blood urea nitrogen (BUN) and urinary protein of 24 h was performed to evaluated renal function. The protein level of X-linked inhibitor of apoptosis protein (XIAP) and Survivin in was detected by Western blotting. The expression of fibronectin and collagen in kidney tissue was determined by immunofluorescence assay. In addition, the activity of p38 MAPK pathway in HK-2 cells was also evaluated. Our results showed that SAA decreased the level of creatinine, BUN and urea protein. The DDPinduced kidney damage was also ameliorated. The down-regulation of XIAP and Survivin in protein induced by DDP was restored by SAA treatment. Moreover, SAA impaired DDP-induced renal fibrosis through inhibiting the expression of fibronectin and collagen. In vitro, SAA could alleviate the increase phosphorylation level of p38 MAPK that induced by DDP in HK-2 cells. In summary, our results showed that SAA has a protective effect against DDP-induced nephrotoxicity. In addition, p38 MAPK signaling pathway might play a important role in this protection effect of SAA. SAA may be useful for preventing nephrotoxicity in cancer patients receiving DDP chemotherapy.