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霉酚酸酯在小鼠胸膜炎模型中的抗氧化作用。

Antioxidant effects of mycophenolate mofetil in a murine pleurisy model.

机构信息

Department of Pharmaceutical Science, Health Sciences Center, University Regional of Blumenau, Itoupava Seca, Blumenau, SC 89000-030, Brazil.

出版信息

Transpl Immunol. 2009 Dec;22(1-2):12-7. doi: 10.1016/j.trim.2009.09.005. Epub 2009 Sep 22.

Abstract

Generation of oxidative stress induced by reactive oxygen species (ROS) and nitrogen (RNS) is believed to be a primary factor in the etiology of various inflammatory diseases. Although, the process of generation of oxygen species is a physiological event, in the inflammatory process this event is increased and produces large amounts of reactive species that leads to lipid peroxidation and to cell death. Mycophenolate mofetil (MMF) is a drug effective in protecting against chronic allograft failure and recently was introduced as an alternative for the treatment of various inflammatory diseases such as glomerulopathies, systemic lupus erythematosus and systemic vasculitis. Based on studies of the anti-inflammatory effect of MMF the aim of this study was to evaluate the effects of MMF on the inhibition of leukocytes and exudation, as well as myeloperoxidase and some antioxidant enzyme activities using carrageenan-induced pleurisy in mice. Our results showed that MMF significantly decreased leukocyte influx (P<0.01), exudation (P<0.01), superoxide dismutase (P<0.05), catalase (P<0.05), glutathione peroxidase (P<0.01), glutathione S-transferase (P<0.01) activities, levels of lipid peroxidation (P<0.05), as well as myeloperoxidase activity (P<0.05) on both phases (4h and 48h) of the inflammatory response induced by carrageenan into the mice pleural cavity. In conclusion, the anti-inflammatory effect of MMF may be, at least in part, via inhibition of ROS and/or NRS overgeneration, and consequently, attenuating the related oxidative stress.

摘要

活性氧(ROS)和氮(RNS)引起的氧化应激的产生被认为是各种炎症性疾病发病的主要因素。虽然氧物种的生成过程是一种生理事件,但在炎症过程中,这一事件会增加,并产生大量的反应性物质,导致脂质过氧化和细胞死亡。霉酚酸酯(MMF)是一种有效预防慢性同种异体移植物衰竭的药物,最近被引入作为治疗各种炎症性疾病的替代药物,如肾小球疾病、系统性红斑狼疮和系统性血管炎。基于 MMF 的抗炎作用研究,本研究旨在评估 MMF 对白细胞和渗出物以及髓过氧化物酶和一些抗氧化酶活性的抑制作用,使用角叉菜胶诱导的小鼠胸膜炎。我们的结果表明,MMF 显著降低白细胞流入(P<0.01)、渗出物(P<0.01)、超氧化物歧化酶(P<0.05)、过氧化氢酶(P<0.05)、谷胱甘肽过氧化物酶(P<0.01)、谷胱甘肽 S-转移酶(P<0.01)活性、脂质过氧化水平(P<0.05)以及髓过氧化物酶活性(P<0.05),在角叉菜胶诱导的小鼠胸膜炎的两个阶段(4 小时和 48 小时)。总之,MMF 的抗炎作用可能至少部分是通过抑制 ROS 和/或 RNS 的过度生成,从而减轻相关的氧化应激。

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