...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy
【24h】

Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy

机译：去铁胺在伴刀豆球蛋白A诱导的肝纤维化中的抗纤维化机制：对干扰素治疗的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Iron-overload is a well-known factor of hepatotoxicity and liver fibrosis, which found to be a common finding among hepatitis C virus patients and related to interferon resistance. We aimed to elucidate the potential antifibrotic effect of deferoxamine; the main iron chelator, and its additional usefulness to interferon-based therapy in concanavalin A-induced immunological model of liver fibrosis. Rats were treated with deferoxamine and/or pegylated interferon-alpha for 6 weeks. Hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed. Concanavalin A induced a significant increase in hepatotoxicity indices and lipid peroxidation accompanied with a significant depletion of total antioxidant capacity, glutathione level and superoxide dismutase activity. Besides, it increased CD4(+) T-cells content and the downstream inflammatory cascades, including NF-kappa B, TNF-alpha, iNOS, COX-2, IL-6 and IFN-gamma. Furthermore, alpha-SMA, TGF-beta 1 and hydroxyproline were increased markedly, which confirmed by histopathology. Treatment with either deferoxamine or pegylated interferon-alpha alone reduced liver fibrosis markers significantly and improved liver histology. However, some of the hepatotoxicity indices and oxidative stress markers did not improve upon pegylated interferon-alpha treatment alone, besides the remarkable increase in IL-6. Combination therapy of deferoxamine with pegylated interferon-alpha further improved all previous markers, ameliorated IL-6 elevation, as well as increased hepcidin expression. In conclusion, our study provides evidences for the potent antifibrotic effects of deferoxamine and the underlying mechanisms that involved attenuating oxidative stress and subsequent inflammatory cascade, as well as the production of profibrogenic factors. Addition of deferoxamine to interferon regimen for HCV patients may offer a promising adjuvant modality to enhance therapeutic response. (C) 2015 Elsevier Inc. All rights reserved.
机译：铁超载是肝毒性和肝纤维化的众所周知的因素，发现这是丙型肝炎病毒患者中的常见发现，并且与干扰素抵抗有关。我们旨在阐明去铁胺的潜在抗纤维化作用。的主要铁螯合剂，以及其在伴刀豆球蛋白A诱导的肝纤维化免疫模型中对基于干扰素的治疗的额外作用。用去铁胺和/或聚乙二醇化干扰素-α治疗大鼠6周。评估肝毒性指数，氧化应激，炎症和肝纤维化指标。伴刀豆球蛋白A诱导肝毒性指数和脂质过氧化作用显着增加，同时总抗氧化能力，谷胱甘肽水平和超氧化物歧化酶活性显着降低。此外，它增加了CD4（+）T细胞含量和下游炎症级联反应，包括NF-κB，TNF-α，iNOS，COX-2，IL-6和IFN-γ。此外，α-SMA，TGF-β1和羟脯氨酸显着增加，这由组织病理学证实。单独用去铁胺或聚乙二醇化干扰素-α治疗可显着降低肝纤维化标志物并改善肝脏组织学。但是，除了IL-6的显着增加外，某些肝毒性指数和氧化应激指标在单独使用聚乙二醇化干扰素-α治疗后并没有改善。去铁胺与聚乙二醇化干扰素-α的联合治疗进一步改善了所有以前的标志物，改善了IL-6的升高，并增加了铁调素的表达。总之，我们的研究为去铁胺的强抗纤维化作用及其潜在的机制提供了证据，这些机制涉及减轻氧化应激和随后的炎症级联反应以及促纤维化因子的产生。 HCV患者在干扰素方案中加入去铁胺可能会为增强治疗反应提供有希望的佐剂。 （C）2015 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号