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克氏锥虫:去铁胺通过抗锥虫作用降低感染小鼠的死亡率和寄生虫血症。

Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect.

机构信息

Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Osvaldo Cruz, Belo Horizonte, MG, Brazil.

出版信息

Exp Parasitol. 2011 Aug;128(4):401-8. doi: 10.1016/j.exppara.2011.05.011. Epub 2011 May 18.

DOI:10.1016/j.exppara.2011.05.011
PMID:21620835
Abstract

Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties.

摘要

去铁胺(DFO)是一种有效的铁螯合剂,已知在正常条件下和氧化应激下可调节炎症并发挥有效的抗氧化作用。许多体外和体内研究表明 DFO 在治疗病毒、细菌和原生动物感染方面的疗效。已知去铁胺可降低小鼠中克氏锥虫感染的强度,即使在治疗过程中不能有效维持贫血或低铁水平。为了进一步阐明这些发现,我们研究了 DFO 对小鼠 T. cruzi 感染结果的作用以及 DFO 对寄生虫的直接影响。用 DFO(5mg/动物/天)治疗感染动物 35 天,从感染前 14 天开始,可降低寄生虫血症和累积死亡率。铁代谢标志物、红细胞计数、白细胞计数或淋巴细胞亚群无显著变化。在体内 T. cruzi 敏感性的快速检测方法中,DFO 也诱导较低的寄生虫血症。至于其对寄生虫的直接影响,DFO 轻微抑制了成纤维细胞培养中的阿米巴原虫和锥虫的生长。台盼蓝染色显示 DFO 对寄生虫活力无影响,仅观察到锥虫的轻微凋亡。然而,检测到寄生虫的运动能力明显下降。总之,DFO 对小鼠 T. cruzi 感染的有益作用似乎与宿主铁代谢无关,且无明显的血液学副作用。通过对寄生虫的直接作用,DFO 具有更有效的杀锥虫作用而非杀锥虫作用。

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