Li Jing, Liu Hui, Jia Yutong, Tuniyazi Xiayidanmu, Liao Xia, Zhao Jinlong, Du Yun, Fang Ziyi, Lü Guodong
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.
Biochem Biophys Res Commun. 2025 Feb 16;749:151365. doi: 10.1016/j.bbrc.2025.151365. Epub 2025 Jan 20.
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.
对乙酰氨基酚（APAP）是一种常用的解热镇痛药。APAP过量是药物性肝损伤和急性肝衰竭（ALF）的主要原因。已证明SW033291在各种疾病的组织再生中发挥作用；然而，其在APAP诱导的肝损伤后促进肝再生的潜力仍未得到研究。因此，本研究通过建立APAP诱导的小鼠急性肝损伤模型，重点探讨SW033291对肝损伤的治疗作用及其机制。结果表明，SW033291治疗可降低血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性，减少肝坏死面积，提高谷胱甘肽（GSH）水平，降低组织丙二醛（MDA）含量，以及肝损伤小鼠中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达水平。它还可以通过提高组织前列腺素E2（PGE2）水平来促进肝细胞增殖并抑制细胞凋亡。总之，SW033291通过促进肝再生、减轻氧化应激和调节炎症反应，显示出改善APAP诱导的小鼠肝损伤的能力，从而成为开发针对急性肝衰竭的治疗干预措施的有希望的候选药物。
