Fluorofenidone protects liver against inflammation and fibrosis by blocking the activation of NF‐κB pathway. Issue 7 (21st June 2021)

• Record Type: Journal Article
• Authors: Tu, Sha; Jiang, Yanzhi; Cheng, Haihua; Yuan, Xiangning; He, Ying; Peng, Yu; Peng, Xiongqun; Peng, Zhangzhe; Tao, Lijian; Yang, Huixiang
• Is Part Of: FASEB journal. Volume 35:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-21
• Subjects: AKF‐PD -- inflammation -- liver fibrosis -- NF‐κB; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002402R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Despite the increasing understanding of the pathophysiology of hepatic fibrosis, the therapies to combat it remain inadequate. Fluorofenidone (AKF‐PD) is a novel pyridone agent able to ameliorate hepatic fibrosis in an experimental hepatic fibrosis model induced by dimethylnitrosamine. However, the underlying mechanism remains to be further elucidated. In light of the critical role of the NF‐κB pathway in inflammation and hepatic fibrosis, together with the preliminary finding that AKF‐PD decreases the release of proinflammatory cytokines in the endotoxemia and unilateral ureteral occlusion model, the aim of this study was to explore whether AKF‐PD exerts an antifibrotic effect in hepatic fibrosis by inhibiting inflammation and suppressing the activation of the NF‐κB pathway in vivo and in vitro. To test this possibility, the effect of AKF‐PD on hepatic fibrosis models induced by both carbon tetrachloride (CCL4 ) and porcine serum (PS) was investigated. Our results showed that AKF‐PD treatment ameliorated hepatic injury and fibrosis in both models. Furthermore, the administration of AKF‐PD induced a robust anti‐inflammatory reaction revealed by the downregulation of the proinflammatory cytokines as well as the suppression of the infiltration of inflammatory cells in the fibrotic liver. The analysis of the mechanism of action demonstrated that the attenuation of the production of proinflammatory cytokines and chemokines mediated by AKF‐PD in vivo and in vitro were accompanied by the suppression in the activation of the NF‐κB signaling pathway. In conclusion, AKF‐PD might be considered as an antifibrotic agent attenuating hepatic inflammation and fibrosis potentially through the suppression of the NF‐κB pathway.