کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5558355 | 1561133 | 2017 | 7 صفحه PDF | دانلود رایگان |
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- Mirtazapine attenuates thioacetamide-induced liver fibrosis in mice.
- Mirtazapine decreases the liver content of TGF-β1 and PKC.
- Mirtazapine reduces the expression of p-Smad3 and p-ERK1/2.
Serotonin (5-HT) has been implicated as a key driver of liver fibrosis, acting via 5-HT2 receptor activation in the hepatic stellate cells. The current study was conducted to investigate the effects of mirtazapine, a 5-HT2A antagonist, in a mouse model of liver fibrosis. Mice received thioacetamide (TAA, 150 mg/kg/biweekly, ip) for nine successive weeks for induction of liver fibrosis. Administration of mirtazapine significantly improved the plasma aminotransferases, reduced hepatic 5-HT concentration and ameliorated TAA-induced liver fibrosis, as demonstrated by reduced portal blood pressure, liver procollagen I content and α alpha smooth muscle actin expression. Moreover, hepatic collagen deposition was markedly decreased in mirtazapine-treated mice as evaluated by Masson's trichrome staining. Mirtazapine provided an antifibrotic environment by decreasing the liver content of transforming growth factor-β1 (TGF-β1), and protein kinase C as well as the expression of phosphorylated-Smad3 (p-Smad) and phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2). Additionally, oxidative stress was largely mitigated by mirtazapine as manifested by decreased liver lipid peroxidation and NADPH oxidase 1 along with glutathione replenishment. The current study indicates that mirtazapine suppressed 5-HT-mediated TGF-β1/Smad3 and ERK1/2 signaling pathways as well as oxidative stress that contribute to the progression of liver fibrosis.
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Journal: Toxicology and Applied Pharmacology - Volume 329, 15 August 2017, Pages 224-230