EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Younan Ren,Ying Chen,Emily H. Tang,Yixin Hu,Bo Niu,Huaduan Liang,Chuchu Xi,Fang Zhao,Zhengyu Cao
Chronic liver diseases (CLD) impact over 800 million people globally, causing about 2 million deaths annually. Arbidol (ARB), an indole-derivative used to treat influenza virus infection, was extensively used during COVID-19 pandemic in China. In recent years, studies have shown that ARB, compared to other antiviral drugs, exhibits greater liver-protective efficacy, indicating a potential hepatoprotective effect beyond its antiviral activity. However, the mechanism remains unclear. In this study, we investigated the impact of ARB on liver injury/fibrosis in bile duct ligated (BDL) mice and its effect on spontaneous and transforming growth factor β1 (TGF-β1)-induced activation of primary cultured hepatic stellate cells (HSCs). Oral administration of ARB significantly ameliorated BDL-induced liver injury/fibrosis as reflected by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced collagen deposition, and diminished mRNA expression of fibrosis markers. ARB notably inhibited spontaneous and TGF-β1-induced activation of primary cultured HSCs. Moreover, ARB also drastically attenuated mRNA expression levels of platelet-derived growth factor receptor ( Pdgfr), transforming growth factor-beta receptor ( Tgfbr ) 1, Tgfbr2, matrix metalloproteinase (Mmp)-2, and Mmp-9 in activated HSCs. We further demonstrate that ARB mitigated Smad2/3 phosphorylation in both TGF-β1 treated HSCs and BDL mice. These data together demonstrate that the therapeutic efficacy of ARB on liver fibrosis is independent of its antiviral activity and likely is achieved by blocking TGF-β1 signaling-mediated HSC activation.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Ziwei Guo,Huan He,Gui Yang,Kunqian Liu,Yanting Xi,Zihui Li,Yu Luo,Zhicheng Liao,Guohua Dao,Xiaomin Ren,Bin Huang,Xuejun Pan
The environmental risks resulting from the increasing antivirals in water are largely unknown, especially in eutrophic lakes, where the complex interactions between algae and drugs would alter hazards. Herein, the environmental risks of the antiviral drug arbidol towards the growth and metabolism of Microcystis aeruginosa were comprehensively investigated, as well as its biotransformation mechanism by algae. The results indicated that arbidol was toxic to Microcystis aeruginosa within 48 h, which decreased the cell density, chlorophyll-a, and ATP content. The activation of oxidative stress increased the levels of reactive oxygen species, which caused lipid peroxidation and membrane damage. Additionally, the synthesis and release of microcystins were promoted by arbidol. Fortunately, arbidol can be effectively removed by Microcystis aeruginosa mainly through biodegradation (50.5% at 48 h for 1.0 mg/L arbidol), whereas the roles of bioadsorption and bioaccumulation were limited. The biodegradation of arbidol was dominated by algal intracellular P450 enzymes via loss of thiophenol and oxidation, and a higher arbidol concentration facilitated the degradation rate. Interestingly, the toxicity of arbidol was reduced after algal biodegradation, and most of the degradation products exhibited lower toxicity than arbidol. This study revealed the environmental risks and transformation behavior of arbidol in algal bloom waters.
研究领域:
环境科学
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水生毒理学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Ziwei Guo,Huan He,Kunqian Liu,Zihui Li,Yanting Xi,Zhicheng Liao,Guohua Dao,Bin Huang,Xuejun Pan
Increasing antivirals in surface water caused by their excessive consumption pose serious threats to aquatic organisms . Our recent research found that the input of antiviral drug arbidol to algal bloom water can induce acute toxicity to the growth and metabolism of Microcystis aeruginosa , resulting in growth inhibition, as well as decrease in chlorophyll and ATP contents. However, the toxic mechanisms involved remained obscure, which were further investigated through transcriptomic analysis in this study. The results indicated that 885–1248 genes in algae were differentially expressed after exposure to 0.01–10.0 mg/L of arbidol, with the majority being down-regulated. Analysis of commonly down-regulated genes found that the cellular response to oxidative stress and damaged DNA bonding were affected, implying that the stress defense system and DNA repair function of algae might be damaged. The down-regulation of genes in porphyrin metabolism, photosynthesis , carbon fixation , glycolysis, tricarboxylic acid cycle , and oxidative phosphorylation might inhibit chlorophyll synthesis, photosynthesis, and ATP supply, thereby hindering the growth and metabolism of algae. Moreover, the down-regulation of genes related to nucleotide metabolism and DNA replication might influence the reproduction of algae. These findings provided effective strategies to elucidate toxic mechanisms of contaminants on algae in algal bloom water.
研究领域:
环境科学
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毒理学
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分子生物学
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水生生态学
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DOI
PubMed
高影响因子
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