A class of imidazolium salts is anti-oxidative and anti-fibrotic in hepatic stellate cells

Ding, Zhaobing; Suhaimi, Nur-Afidah Mohamed; Kng, Yin Ling; Zhang, Yugen; Zhuo, Lang

doi:10.1080/10715760903137002

Cited by 26 publications

(20 citation statements)

References 25 publications

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“…10 Here, we confirmed that DPIM at much lower concentrations (50, 100, and 200 mM) for 48 h also dose dependently suppressed the expression of the fibrogenic Col1a1 gene, but not the a-SMA (Figures 1b-d Supplementary Figure 2a). However, DPIM treatment (10, 100, 200 mM for 48 h) failed to significantly inhibit the proliferation of HSC-T6 cells (Supplementary Figure 2b), albeit a slight decrease in proliferation was achieved at 200 mM (P ¼ 0.08, compared with 0 mM).…”

Section: Effects Of Dpim In Hsc-t6 Cellssupporting

confidence: 72%

“…10 Primary antibodies used for the western blots were a-SMA (1:1000 dilution, Sigma), a-Tubulin (1:2000 dilution, Santa Cruz Biotech, USA), TIMP-1 (1:500 dilution, sc-80363, Santa Cruz Biotech), MCP-1 (1:500 dilution, sc-28879, Santa Cruz Biotech).…”

Section: Protein Extraction Sds-page and Immunoblotmentioning

confidence: 99%

“…10 To ensure sampling accuracy, at least six different areas from the left and middle lobes of each liver were included for imaging and quantification. We chose to use the Sirius Red stain to better visualize the assembled collagen fibers, since degraded collagen fragments is also reflected in the hydroxyproline assay.…”

Section: Cell Culturementioning

confidence: 99%

“…surgery was performed as previously described. 10 The BDL mice and sham-operated mice were assigned to five different treatment groups (Supplementary Figure 3), with 6-8 mice in each group. All mice (sham or BDL) had free access to drinking water with (0.5, 0.75, or 1 g/l) or without DPIM, as indicated in Supplementary Figure 3.…”

Section: Cell Culturementioning

confidence: 99%

“…8,9 Despite our extensive knowledge on the importance of inflammation and ECM remodeling in fibrogenesis and resolution, no effective drug therapy has been reported by simultaneously targeting these two key aspects with small molecules. In a recent study, 10 we have identified several imidazolium salts (IMSs) that can reduce collagen production in a cell-based screening, and further shown that one of the IMSs, 1,3-bisbenzylimidazolium bromide (DBZIM), can reduce the collagen content in the liver of a mouse cholestasis model. In the same cell-based screen, we also uncovered a simpler IMS, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), which is devoid benzyl substituent, with an antifibrotic effect.…”

mentioning

confidence: 99%

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An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

Ding

Kng

Yang

et al. 2011

Laboratory Investigation

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Hepatic fibrosis is the result of chronic liver injuries underlined by diverse etiologies. The massive accumulation of extracellular matrix (ECM) proteins during fibrogenesis leads to structural distortion and functional disruption of the liver. There is currently no effective standard treatment for liver fibrosis. We previously identified a class of imidazolium salts (IMSs) with anti-fibrotic properties in a cell-based screen. In this report, we investigated the anti-fibrotic efficacy and mechanisms of a small IMS, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), in a hepatic fibrosis model induced by bile duct ligation (BDL) in mice. The orally available DPIM was administered to BDL mice via drinking water at three concentrations (0.5, 0.75, and 1 g/l) for 4 weeks. We observed a significant reduction in inflammation and collagen deposition in the liver, which could be mediated by a reduction in the expression of monocyte chemoattractant protein-1 (MCP-1) and by an enhancement in the matrix metalloproteinase-mediated ECM remodeling. The current findings highlight the importance for simultaneously targeting multiple pathways to more effectively attenuate and resolve liver fibrosis and warrant further studies on this compound in additional models of hepatic fibrosis.

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Section: Effects Of Dpim In Hsc-t6 Cellssupporting

confidence: 72%

Section: Protein Extraction Sds-page and Immunoblotmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

Ding

Kng

Yang

et al. 2011

Laboratory Investigation

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High-Fructose, Medium Chain Trans Fat Diet Induces Liver Fibrosis and Elevates Plasma Coenzyme Q9 in a Novel Murine Model of Obesity and Nonalcoholic Steatohepatitis†

et al. 2010

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Diets high in saturated fat and fructose have been implicated in the development of obesity and nonalcoholic steatohepatitis (NASH) in humans. We hypothesized that mice exposed to a similar diet would develop NASH with fibrosis associated with increased hepatic oxidative stress that would be further reflected by increased plasma levels of the respiratory chain component, oxidized coenzyme Q9 ( ox CoQ9). Adult male C57Bl/6 mice were randomly assigned to chow, high-fat (HF), or high-fat high-carbohydrate (HFHC) diets for 16 weeks. The chow and HF mice had free access to pure water, whereas the HFHC group received water with 55% fructose and 45% sucrose (wt/vol). The HFHC and HF groups had increased body weight, body fat mass, fasting glucose, and were insulin-resistant compared with chow mice. HF and HFHC consumed similar calories. Hepatic triglyceride content, plasma alanine aminotransferase, and liver weight were significantly increased in HF and HFHC mice compared with chow mice. Plasma cholesterol (P < 0.001), histological hepatic fibrosis, liver hydroxyproline content (P 5 0.006), collagen 1 messenger RNA (P 5 0.003), CD11b-F4/801Gr11 monocytes (P < 0.0001), transforming growth factor b1 mRNA (P 5 0.04), and a-smooth muscle actin messenger RNA (P 5 0.001) levels were significantly increased in HFHC mice. Hepatic oxidative stress, as indicated by liver superoxide expression (P 5 0.002), 4-hydroxynonenal, and plasma ox CoQ9 (P < 0.001) levels, was highest in HFHC mice. Conclusion: These findings demonstrate that nongenetically modified mice maintained on an HFHC diet in addition to developing obesity have increased hepatic ROS and a NASH-like phenotype with significant fibrosis. Plasma ox CoQ9 correlated with fibrosis progression. The mechanism of fibrosis may involve fructose inducing increased ROS associated with CD11b1F4/801Gr11 hepatic macrophage aggregation, resulting in transforming growth factor b1-signaled collagen deposition and histologically visible hepatic fibrosis. (HEPATOLOGY 2010;52:934-944) Abbreviations: a-SMA, a-smooth muscle actin; ALT, alanine aminotransferase; ANOVA, analysis of variance; DHE, dihydroethidium; HFHC, high-fat, highcarbohydrate; HF, high-fat; HOMA-IR, homeostasis model assessment of insulin resistance; mRNA, messenger RNA; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; ox CoQ9, oxidized coenzyme Q9; PCR, polymerase chain reaction; red CoQ9, reduced coenzyme Q9; ROS, reactive oxygen species; RT-PCR, reverse-transcription PCR; TG, triglyceride; TGF-b1, transforming growth factor b1.From the

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Investigating the Biological Activity of Imidazolium Aurate Salts

et al. 2019

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We report herein the biological activities of several imidazolium aurate(I) salts. The cytotoxicity on three cell‐lines (i. e. Hela, H460 and 3T3), enzyme inhibition on a panel of five enzymes (i. e. prolyl endopeptidase, butyrylcholinesterase, tyrosinase, dipeptidyl peptidase and carbonic anhydrase), iron chelation and in vitro Leishmanicidal assay for promastigotes are described. A comparison with other data found in the literature using similar standards to our control experiment is also discussed. Finally, all these data lead us to establish some structure‐activity correlations and to determine the potential importance of the gold moiety in these salts.

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A class of imidazolium salts is anti-oxidative and anti-fibrotic in hepatic stellate cells

Cited by 26 publications

References 25 publications

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

An orally available small imidazolium salt ameliorates inflammation and fibrosis in a murine model of cholestasis

High-Fructose, Medium Chain Trans Fat Diet Induces Liver Fibrosis and Elevates Plasma Coenzyme Q9 in a Novel Murine Model of Obesity and Nonalcoholic Steatohepatitis†

Investigating the Biological Activity of Imidazolium Aurate Salts

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