Ageratina adenophora induces mice hepatotoxicity via ROS-NLRP3-mediated pyroptosis. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Sun, Wei; Zeng, Chaorong; Liu, Shanshan; Fu, Jie; Hu, Liwen; Shi, Zhen; Yue, Dong; Ren, Zhihua; Zhong, Zhijun; Zuo, Zhicai; Cao, Suizhong; Peng, Guangneng; Deng, Junliang; Hu, Yanchun
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 8
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-34492-7
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Increasing evidences have demonstrated thatAgeratina adenophora (A. adenophora ) can cause hepatotoxicity of animals. Liver is an important site in immune regulation and inflammatory responses. However, the information about hepatotoxicity induced byA. adenophora in relation to inflammation is still finite. To investigate the underlying mechanism, we conducted animal experiments with different dosage ofA. adenophora . Mice were randomly divided into 4 groups and administrated with 0%, 10%, 20% and 30% levels ofA. adenophora pallet diet in control, group A, B and C, respectively. The results showed thatA. adenophora caused hepatotoxicity as revealed by increasing alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase. Then, the reactive oxygen species (ROS) levels were shown to be elicited byA. adenophora through flow cytometry assay in a dose-dependent manner. Furthermore, pyroptosis was activated byA. adenophora, which was characterized by increasing protein and mRNA levels of caspase-1, gasdermin D and interleukin-1β. Notably, ROS down-stream factors, including nod-like receptor inflammasome protein 3 and nuclear factor-κB, were also activated byA. adenophora . These data demonstrated thatA. adenophora caused liver inflammatory injury and induced hepatocyte pyroptosis by activating NLRP3 inflammasome, which was triggered by elevating ROS production levels. This research might provide new insights into the mechanism of hepatotoxicity induced byA. adenophora .