期刊
FREE RADICAL RESEARCH
卷 43, 期 10, 页码 899-912出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715760903137002
关键词
Imidazolium salts; hepatic stellate cells; hepatic fibrosis; glutathione; TGF-1; anti-oxidant
资金
- Institute of Bioengineering and Nanotechnology (IBN) (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)
A class of imidazolium salts (IMSs) is routinely used in organic synthetic chemistry as precursors to generate N-heterocyclic carbenes (NHCs) with catalytic activity. However, their biological properties are largely unknown. The current study investigates the biological activity of a typical NHC precursor DBZIM and its trimer TDBZIM in hepatic stellate cells (HSCs), which is an in vitro model for studying liver fibrosis. The results show that HSCs treated with IMSs have an enhanced GSH/GSSG ratio and a reduced level of reactive oxygen species (ROS), which may consequently contribute to the attenuation in gene expression of fibrogenic molecules such as smooth muscle actin- (SMAA), transforming growth factor-beta 1 (TGF-1), procollagen I(I) and fibronectin. Further, the in vivo experiments demonstrate that DBZIM is an anti-fibrotic agent in a mouse model of liver fibrosis. These findings suggest that the versatile IMSs could be a potential source for developing novel therapeutics to treat liver fibrosis and other fibrogenic disorders caused by oxidative stress and TGF-1 mal-signalling.
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