Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats

Abstract

The aim of this study was to explore the role of the NOD-like receptor family, pyrin domain containing (NLRP3) inflammasome and autophagy in Astragaloside IV (AS IV)-mediated protection against cisplatin-induced liver and kidney injury in rats. Rats were intraperitoneally administered cisplatin at a dose of 15 mg/kg and orally administered AS IV for 7 days. Histopathological and biochemical analysis were used to assess liver and kidney function. The levels and localization of NLRP3 and autophagy-associated protein were determined by Western blot and immunohistochemistry. Intraperitoneal administration of cisplatin induced acute liver and kidney injury, and activated the NLRP3 inflammasome. Oral administration of AS IV for 7 days protected against the cisplatin-induced injury, and inhibited the expression of NLRP3, as well as the production of pro-inflammatory cytokines. Moreover, cisplatin modulated the conversion of LC3 II and the expression of p62, thereby inhibiting autophagy and the activation of NLRP3. AS IV effectively protected against cisplatin-induced injury by inducing autophagy and limiting the expression of NLRP3. Autophagy-mediated NLRP3 inhibition might play a crucial role in AS IV-mediated protection against cisplatin-induced toxicity. These results provide evidence of a novel therapeutic that may be used to alleviate the toxic effects of platinum-based chemotherapy.