Trehalose attenuates mitochondrial dysfunction in cisplatin‐induced acute kidney injury by activating autophagy

Abstract

ObjectiveCisplatin, an anticancer drug, always lead to nephrotoxicity via causing mitochondrial dysfunction. As a major catabolic pathway, autophagy has been proved that could protect against cisplatin‐induced acute kidney injury (AKI). Base on the activation of autophagy induced by trehalose, we aimed to investigated whether trehalose could alleviate mitochondrial dysfunction and kidney injury in mice though autophagy‐lysosome mediated clearance of damaged mitochondria.MethodsMice were administered a single intraperitoneal (i.p.) injection of cisplatin 16mg/kg to induce AKI, then mice were treated with PBS or trehalose (i.p.). In vitro, HK2 cells were treated with cisplatin 16mg/kg in the presence or absence of trehalose. To evaluate mitochondrial bioenergetic, mitochondrial morphology, membrane potential and ATP content were detected.ResultsIn vivo, comparing with the normal mice, BUN and Crea were significantly increased in AKI mice, while decreased after the treatment with trehalose, indicating that trehalose could alleviate kidney injury in AKI mice. In vitro, along with the activation of autophagy (elevated expression of LC3 II and ATG5), mitochondrial fragmentation, depolarization, and reduced ATP generation induced by cisplatin were markedly inhibited in trehalose‐treated HK2 cells. Moreover, the double immunofluorescence staining results showed that the co‐localization between mitochondria and LC3 was increased, indicating that the mitophagy was induced. In addition, we found that the protective effect of trehalose was largely abolished when the autophagy process was inhibited by HCQ.ConclusionThese results indicated that trehalose can ameliorate cisplatin‐induced mitochondrial dysfunction by activating autophagy, and thus it might be a promising therapy to acute kidney injury.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.