A class of imidazolium salts is anti-oxidative and anti-fibrotic in hepatic stellate cells.
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-alpha (SMAA), transforming growth factor-beta 1 (TGF-beta1), procollagen alphaI(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-beta1 mal-signalling.
Zhang
Chunyan
C
Institute of Bioengineering and Nanotechnology, The Nanos, Singapore.
Ding
Zhaobing
Z
Suhaimi
Nur-Afidah Mohamed
NA
Kng
Yin Ling
YL
Zhang
Yugen
Y
Zhuo
Lang
L
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D048288:Imidazolines / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
D000975:Antioxidants; D048288:Imidazolines; D017382:Reactive Oxygen Species; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D005978:Glutathione; D019803:Glutathione Disulfide