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.

The Role of Astragaloside IV against Cerebral Ischemia/Reperfusion Injury: Suppression of Apoptosis via Promotion of P62-LC3-Autophagy

“…Moreover, Astragaloside IV could further enhance autophagy by increasing the LC3II/LC3I ratio and inhibiting the pP62 expression. Liu [55], Wang [56] and Qu [57] confirmed that Astragaloside IV could activate autophagy in human degenerative chondrocytes and renal disease, respectively. We found that Astragaloside IV can activate autophagy in HT22 cells after OGD/R, it is consistent with the results of the above studies [55,56,57] about the effects of Astragaloside IV on autophagy.…”

Role of Inflammasomes in Kidney Diseases via Both Canonical and Non-canonical Pathways

“…However, SIRT3 can protect from the AKI caused by cisplatin by inducing autophagy (Zhao et al, 2018). Moreover, Astragaloside IV can protect from cisplatin-induced kidney injury by inducing the autophagy and suppressing the NF-kB signal pathway, thereby down-regulating the expression of NLRP3 inflammasome (Qu et al, 2019). Moreover, the caspase inhibition can reduce the production of caspase-1 and IL-1β, and thus protect from the cisplatin-induced kidney injury (Lee et al, 2015).…”

L-Carnitine Mitigates Oxidative Stress and Disorganization of Cytoskeleton Intermediate Filaments in Cisplatin-Induced Hepato-Renal Toxicity in Rats

“…Although cisplatin (CP) [ cis -diamminedichloroplatinum (II), CDDP], is potent anticancer medication use to treat a variety of tumors including testicular, ovarian, bladder, and lung ( Ibrahim et al., 2016 ; Karwasra et al., 2016 ). Several recent studies recorded that the CP induces hepatotoxicity ( Abdellatief et al., 2017 ; Qu et al., 2019 ; Abdel-Daim et al., 2020 ; Hwang et al., 2020 ) and nephrotoxicity ( Abdel-Daim et al., 2017 ; Abdel-Razek et al., 2020 ; Abo-Elmaaty et al., 2020 ; Sadeghi et al., 2020 ). Miller et al.…”