SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice

Jing Li; Hui Liu; Yutong Jia; Xiayidanmu Tuniyazi; Xia Liao; Jinlong Zhao; Yun Du; Ziyi Fang; Guodong Lü

doi:10.1016/j.bbrc.2025.151365

SW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice

Biochem Biophys Res Commun. 2025 Jan 20:749:151365. doi: 10.1016/j.bbrc.2025.151365. Online ahead of print.

Authors

Jing Li¹, Hui Liu², Yutong Jia¹, Xiayidanmu Tuniyazi¹, Xia Liao¹, Jinlong Zhao¹, Yun Du¹, Ziyi Fang³, Guodong Lü⁴

Affiliations

¹ College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
² State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
³ College of Life Sciences and Technology, Xinjiang University, Urumqi, 830054, Xinjiang, China.
⁴ College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China. Electronic address: lgd_xj@xjmu.edu.cn.

PMID: 39855045
DOI: 10.1016/j.bbrc.2025.151365

Abstract

Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined. Thus, this study focused on exploring the therapeutic impacts and mechanisms of SW033291 on liver damage by establishing models of APAP-induced acute liver injury in mice. The results showed that treatment with SW033291 reduces serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, decreases the area of hepatic necrosis, increases glutathione (GSH) levels, and decreases tissue malondialdehyde (MDA) content, as well as the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in mice with liver injury. It could also promote hepatocyte proliferation and inhibit apoptosis by increasing tissue prostaglandin E2 (PGE2) levels. In conclusion, SW033291 demonstrates the capacity to ameliorate APAP-induced hepatic injury in mice by fostering liver regeneration, attenuating oxidative stress, and modulating inflammatory responses, thereby presenting itself as a promising candidate for the development of therapeutic interventions targeting acute liver failure.

Keywords: Acetaminophen; Inflammation response; Liver injury; Oxidative stress; SW033291.