Aluminum activates NLRP3 inflammasome-mediated pyroptosis via reactive oxygen species to induce liver injury in mice

Abstract

Aluminum (Al) exposure can lead to oxidative stress and liver inflammatory injury in mice. The overproduction of reactive oxygen species (ROS) activates the NLRP3 inflammasome and further induces liver pyroptosis. However, the participation of pyroptosis in inducing Al-mediated liver injury and the underlying regulatory mechanisms remain largely unclear. Herein, a mice model of subchronic Al exposure was established to investigate the role of pyroptosis in Al-induced liver injury. Then, MCC950 and N-acetylcysteine were used to inhibit NLRP3 inflammasome-mediated pyroptosis and ROS production for exploring the role and the underlying mechanisms of pyroptosis in determining Al-induced liver injury. It was confirmed that Al induced hepatocyte pyroptosis in mice, and that NLRP3 inflammasome-mediated pyroptosis plays a damaging role in Al-induced liver injury. ROS promotes pyroptosis in an Al-induced liver injury model by activating the NLRP3 inflammasome. Collectively, it was shown that ROS promotes pyroptosis to aggravate Al-induced liver injury by activating the NLRP3 inflammasome.