5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas' disease
5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas' disease
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DOI：
10.1016/j.imlet.2009.02.002
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发表时间：
2009-03-24
影响因子：
4.4
通讯作者：
Pinge-Filho, Phileno
中科院分区：
文献类型：
--
作者：
Borges, Celso Luiz;Cecchini, Rubens;Pinge-Filho, Phileno
恰加斯病伴随着严重的贫血和氧化应激，这可能会导致死亡。在这项研究中，我们研究了5-脂氧合酶(5-LO)在控制实验性克氏锥虫感染时与红细胞氧化损伤相关的寄生虫和贫血中的作用。将野生型C57BL/6、129Sv小鼠、去甲二氢愈创木酸(NDGA，5-LO抑制剂)、5-LO酶基因(5-LO-/-)和诱导型一氧化氮合酶基因(iNOS-/-)缺失的小鼠分别感染克氏支原体Y株。5-LO的损伤导致感染小鼠血液中的类鞭毛体和心脏中的无鞭毛体数量增加。我们通过测量氧摄取量、诱导时间和叔丁基氢过氧化氢(TBH)处理后的化学发光来评估红细胞的氧化应激。我们的结果表明，5-LO代谢物在小鼠克氏支原体感染的早期阶段增加了红细胞的脂质过氧化水平。NDGA对感染C57BL/6 T的小鼠红细胞的氧化损伤有一定的抑制作用，但对感染iNOS的小鼠无明显影响，说明NDGA的作用依赖于内源性一氧化氮(NO)。此外，我们的结果表明，5-LO代谢物不直接参与感染小鼠的贫血的发展。我们的结论是，5-LO产物不仅在体内控制心脏组织寄生虫，即宿主对T ruzi急性感染的抵抗力，而且在感染的情况下，还在红细胞氧化应激中发挥重要作用，这是一种NO依赖的效应。(C)2009爱思唯尔B.V.保留所有权利。
Chagas' disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO-/-) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T cruzi. impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T cruzi-infected mice but not in C57BL/6 iNOS-/- infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T cruzi in vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect. (C) 2009 Elsevier B.V. All rights reserved.