College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China.
College of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
Int Immunopharmacol. 2023 Jan;114:109527. doi: 10.1016/j.intimp.2022.109527. Epub 2022 Dec 19.
Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-β1 (TGF-β1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-β1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.
肝纤维化是由慢性肝损伤和自我修复引起的一种病理变化，是慢性肝病向肝硬化甚至肝癌发展的必然阶段。肝星状细胞（HSCs）的激活是肝纤维化发展的核心事件，阻断 HSCs 的激活已被证明可以减轻肝纤维化。罗硝唑是一种有机砷添加剂，具有抗生素作用、促进生长和提高饲料效率，广泛应用于畜牧业和动物生产。本研究旨在评估罗硝唑对肝纤维化的治疗作用，并探讨其可能的机制。我们发现罗硝唑可以抑制转化生长因子-β1（TGF-β1）诱导的 HSCs 激活，减弱其迁移能力。此外，罗硝唑给药可显著改善 CCl4 诱导的小鼠肝纤维化，改善肝功能，减少细胞外基质（ECM）的沉积。机制研究表明，罗硝唑特异性抑制 TGF-β1/Smad 信号通路的激活，但对 MAPK 和 PI3K/AKT 通路没有影响。这些结果表明，罗硝唑对肝纤维化具有保护作用，为肝纤维化的治疗提供了新的候选药物。
