Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Cantoblanco, Madrid, Spain.
Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
PLoS Negl Trop Dis. 2018 Jan 16;12(1):e0006179. doi: 10.1371/journal.pntd.0006179. eCollection 2018 Jan.
Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs.
克氏锥虫引起的恰加斯病是一种被忽视的疾病，影响着拉丁美洲约 700 万人，由于移民，这种疾病最近在其他大洲出现。由于在感染小鼠中，血浆 L-精氨酸耗竭，因此在有或没有 L-精氨酸补充以及使用特定的诱导型一氧化氮合酶（iNOS）抑制剂 1400W 治疗的情况下，测试了对感染结果的影响。我们发现，感染小鼠的心脏和血浆中的 L-精氨酸和瓜氨酸水平降低，而内源性 iNOS 抑制剂不对称二甲基精氨酸的水平升高。此外，L-精氨酸补充可降低寄生虫血症和心脏寄生虫负担，改善临床评分和生存率。L-精氨酸补充可增加心脏组织和血浆中的一氧化氮产生，而 iNOS 的药理抑制则会导致寄生虫血症增加和临床评分恶化。有趣的是，补充 L-精氨酸可改善小鼠的心电图，表明其可调节感染和心脏功能，因此可能是一种潜在的病理生物标志物。更重要的是，L-精氨酸可能单独或与其他抗寄生虫药物联合用于治疗 T. cruzi 感染。
