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别嘌呤醇可有效改变小鼠克氏锥虫感染的病程。

Allopurinol is effective to modify the evolution of Trypanosoma cruzi infection in mice.

作者信息

Gobbi Paola, Lo Presti María S, Fernández Alicia R, Enders Julio E, Fretes Ricardo, Gea Susana, Paglini-Oliva Patricia A, Rivarola Héctor W

机构信息

Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000, Córdoba, Argentina.

出版信息

Parasitol Res. 2007 Oct;101(5):1459-62. doi: 10.1007/s00436-007-0644-2. Epub 2007 Jul 10.

Abstract

There is a real need for new and less toxic drugs for the treatment of Chagas disease, as nifurtimox and benznidazole are effective but toxic and provoke unpleasant side effects, especially in adult patients. Allopurinol, commonly used to treat the hiperuricemia, is also used by the Trypanosoma cruzi's hypoxantine guanine fosforyltransferase as an alternative substrate incorporating it into the parasite's ribonucleic acid, provoking the death of the parasite. However, the results of using allopurinol as chemotherapy for Chagas disease are not clear. For that, we investigated the evolution of the T. cruzi infection in mice treated with allopurinol (5, 10 or 15 mg/kg for 90 days) obtaining a reduction in the parasitaemia (p<0.05), no electrocardiographic alterations (p<0.05) and a conserved myocardial and cardiac beta-receptors' affinity values with the highest dose of the drug, compared to those of the uninfected mice. Cruzipain immunoglobulin G levels remained high in all the groups as well as the survival (70%, 90 days post-infection). Allopurinol prevented the acute phase evolving into the chronic cardiac disease.

摘要

治疗恰加斯病确实需要新型且毒性较小的药物,因为硝呋替莫和苯硝唑虽有效但有毒性,并会引发不适的副作用,尤其是在成年患者中。常用于治疗高尿酸血症的别嘌呤醇,也会被克氏锥虫的次黄嘌呤鸟嘌呤磷酸转移酶用作替代底物,将其掺入寄生虫的核糖核酸中,从而导致寄生虫死亡。然而,将别嘌呤醇用作恰加斯病化疗药物的结果尚不清楚。为此,我们研究了用别嘌呤醇(5、10或15毫克/千克,持续90天)治疗的小鼠体内克氏锥虫感染的演变情况,结果发现寄生虫血症有所降低(p<0.05),未出现心电图改变(p<0.05),且与未感染小鼠相比,使用最高剂量药物时心肌和心脏β受体的亲和力值保持不变。所有组中的克鲁齐派酶免疫球蛋白G水平以及存活率(感染后90天为70%)均保持较高。别嘌呤醇可防止急性期发展为慢性心脏病。

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