Rosiglitazone ameliorates acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome.

Abstract

Acute hepatic injury is a common liver disease in clinical practice. Drugs with antioxidant activity exhibit a great potential for alleviating liver injury. The present study aimed to explore the role of rosiglitazone (RSG), a previously reported compound with anti-inflammatory properties, in hepatic injury. Kunming mice were divided into the following four groups: The control group; the RSG group; the carbon tetrachloride (CCl4) group; and the RSG + CCl4 group. Hepatic injury was confirmed by histological examination of the liver. In addition, the serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and those of the biochemical indices superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), NO and reactive oxygen species (ROS) were measured in each group of mice. Additionally, the levels of inflammatory factors and apoptosis-related proteins, as well as the activity of the related signaling pathways, were evaluated. The results showed that RSG could reverse the CCl4-mediated decrease in the levels of SOD, CAT and GSH, and increase in the levels of ALT, AST, MDA, NO and ROS. Furthermore, treatment with RSG could reduce the expression levels of inflammation- and apoptosis-related proteins, thus suggesting that RSG could attenuate inflammation and liver cell apoptosis. Additionally, treatment with RSG promoted the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, upregulated peroxisome proliferator-activated receptor γ and inhibited activation of the inflammasome NOD-like receptor protein 3 (NLRP3). In conclusion, the current study demonstrated that RSG could ameliorate acute hepatic injury via activating the Nrf2 signaling pathway and inhibiting activation of the NLRP3 inflammasome. The findings of the present study partly uncovered the mechanism underlying the effect of RSG on hepatic injury, thus supporting the application of RSG in clinical practice.