Abstract

CASTRO, José Alberto; MONTALTO DE MECCA, María; DIAZ GOMEZ, María Isabel  and  CASTRO, Gerardo Daniel. Chagas disease: The contribution of the Center for Toxicological Research. Acta bioquím. clín. latinoam. [online]. 2015, vol.49, n.1, pp.73-82. ISSN 0325-2957.

Chemotherapy of Chagas disease is currently performed by the use of only two drugs: Nifurtimox and Benznidazole. Nifurtimox is a nitrofurane and Benznidazole is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is now widely accepted. However, their use in the treatment of the chronic phase is not without serious consequences. The side effects of both drugs are a major drawback in their use and often force physicians to stop treatment. In the case of Nifurtimox, experimental toxicity studies showed neurotoxicity, testicular damage, ovarian toxicity and deleterious effects in heart, breast tissue, adrenals, colon and esophagus. Benznidazole deleterious effects were observed in adrenals, colon and esophagus. It also inhibits the metabolism of various xenobiotics transformed by cytochrome P450 and its metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and in some studies, they demonstrated to be carcinogenic or tumorigenic. Toxic effects of both drugs are dependent on the enzymatic reduction of the nitro group. This paper summarizes this laboratory’s activity in an effort to understand the mechanisms of these drugs’ toxic action.

Keywords : Benznidazole; Nifurtimox; Chagas’ disease; Chemotherapy; Chemoprophylaxis; Gentian violet; American tripanosomiasis.

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