ROS/RNS as molecular signatures of chronic liver diseases

Zhaodi Che; Ziyuan Zhou; Si-Qi Li; Lei Gao; Jia Xiao; Nai-Kei Wong

doi:10.1016/j.molmed.2023.08.001

ROS/RNS as molecular signatures of chronic liver diseases

Trends Mol Med. 2023 Nov;29(11):951-967. doi: 10.1016/j.molmed.2023.08.001. Epub 2023 Sep 11.

Authors

Zhaodi Che¹, Ziyuan Zhou², Si-Qi Li³, Lei Gao⁴, Jia Xiao⁵, Nai-Kei Wong⁶

Affiliations

¹ Clinical Research Institute, Institute of Obesity and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou 510000, China.
² National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China; Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
³ Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
⁴ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510000, China.
⁵ Clinical Research Institute, Institute of Obesity and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou 510000, China; Shandong Provincial Key Laboratory for Clinical Research of Liver Diseases, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao 266001, China. Electronic address: edwinsiu@connect.hku.hk.
⁶ Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Shantou 515041, China. Electronic address: wongnk@stu.edu.cn.

PMID: 37704494
DOI: 10.1016/j.molmed.2023.08.001

Abstract

The liver can succumb to oxidant damage during the development of chronic liver diseases. Despite their physiological relevance to hepatic homeostasis, excessive reactive oxygen/nitrogen species (ROS/RNS) production under pathological conditions is detrimental to all liver constituents. Chronic oxidative stress coupled to unresolved inflammation sets in motion the activation of profibrogenic hepatic stellate cells (HSCs) and later pathogenesis of liver fibrosis, cirrhosis, and liver cancer. The liver antioxidant and repair systems, along with autophagic and ferroptotic machineries, are implicated in the onset and trajectory of disease development. In this review, we discuss the ROS/RNS-related mechanisms underlying liver fibrosis of distinct etiologies and highlight preclinical and clinical trials of antifibrotic therapies premised on remediating oxidative/nitrosative stress in hepatocytes or targeting HSC activation.

Keywords: antifibrotic drugs; chronic liver diseases; hepatic fibrogenesis; oxidative stress; reactive nitrogen species (RNS); reactive oxygen species (ROS).

Publication types

Review