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在对抗克氏锥虫感染小鼠的氧化/亚硝化应激及心脏病方面,非甾体抗炎药比抗氧化疗法更有效。

Nonsteroidal anti-inflammatory is more effective than anti-oxidant therapy in counteracting oxidative/nitrosative stress and heart disease in T. cruzi-infected mice.

作者信息

Novaes Rômulo D, Santos Eliziária C, Fialho Maria DO Carmo Q, Gonçalves Wagner G, Sequetto Priscila L, Talvani André, Gonçalves Reggiani V

机构信息

Department Structural Biology,Federal University of Alfenas,MG 37130-000,Brazil.

School of Medicine, Federal University of Jequitinhonha and Mucuri Valleys,MG 39100-000,Brazil.

出版信息

Parasitology. 2017 Jun;144(7):904-916. doi: 10.1017/S0031182016002675. Epub 2017 Jan 30.

DOI:10.1017/S0031182016002675
PMID:28134069
Abstract

We compared the relevance of ibuprofen, vitamins C and E to control oxidative/nitrosative stress and heart disease in mice infected by Trypanosoma cruzi. Swiss mice were randomized into five groups: control, uninfected; infected without treatment; and infected treated with vitamins C, E or ibuprofen. Animals were inoculated with 2000 trypomastigote forms of T. cruzi. After 20 days, infected mice presented reduced vitamin C and E tissue levels, high cytokines (interferon gamma, tumour necrosis factor-α, interleukin 10 and chemokine ligand 2), prostaglandin F2α (PGF2α ) and nitric oxide (NO) cardiac production, intense myocarditis and reactive tissue damage, which was directly correlated with the intensity of the inflammatory infiltrate and the degree of pathological cardiac remodelling. Vitamins C and E supplementation were irrelevant to counteract reactive tissue damage and myocarditis in infected animals. Conversely, ibuprofen reduced tissue levels of cytokines, PGF2α and NO, as well as lipid and protein oxidation, antioxidant enzyme activity and the cardiac damage, without interfering with heart parasitism. Our results do not support the applicability of vitamin C and E supplementation in the management of acute Chagas cardiomyopathy. By controlling the inflammatory infiltrate, anti-inflammatory-based therapy proved to be a more rational strategy than a direct antioxidant therapy in attenuating oxidative/nitrosative stress and cardiac damage.

摘要

我们比较了布洛芬、维生素C和维生素E在控制克氏锥虫感染小鼠的氧化/亚硝化应激及心脏病方面的相关性。将瑞士小鼠随机分为五组:对照组,未感染组;未治疗的感染组;以及用维生素C、维生素E或布洛芬治疗的感染组。给动物接种2000个克氏锥虫的锥鞭毛体形式。20天后,感染小鼠的维生素C和E组织水平降低,细胞因子(干扰素γ、肿瘤坏死因子-α、白细胞介素10和趋化因子配体2)、前列腺素F2α(PGF2α)和一氧化氮(NO)的心脏生成量升高,出现严重心肌炎和反应性组织损伤,这与炎性浸润的强度和病理性心脏重塑的程度直接相关。补充维生素C和E与抵消感染动物的反应性组织损伤和心肌炎无关。相反,布洛芬降低了细胞因子、PGF2α和NO的组织水平,以及脂质和蛋白质氧化、抗氧化酶活性和心脏损伤,且不影响心脏寄生虫感染情况。我们的结果不支持补充维生素C和E在急性恰加斯心肌病管理中的适用性。通过控制炎性浸润,基于抗炎的疗法在减轻氧化/亚硝化应激和心脏损伤方面被证明是比直接抗氧化疗法更合理的策略。

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