Benefits of Ascorbic Acid in Association with Low-Dose Benznidazole in Treatment of Chagas Disease.
Antimicrob Agents Chemother
; 62(9)2018 09.
Article
em En
| MEDLINE
| ID: mdl-29987143
ABSTRACT
The acute phase of Chagas disease (CD) is characterized by high parasitic proliferation and intense inflammation, exacerbating the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These reactive molecules are also increased by the metabolism of the nitroheterocyclic compounds benznidazole (BZ) and nifurtimox, the only drugs available for the treatment of CD. This oxidative environment, associated with the intracellular multiplication of Trypanosoma cruzi, leads to tissue destruction, triggering the pathogenic process. Both drugs have limited efficacy and serious side effects, which demonstrates the need to seek alternative therapies. Due to the difficulty in developing new drugs, reviewing therapeutic regimens appears advantageous, and the use of BZ in low doses associated with antioxidants, such as ascorbic acid (AA), would be a valid alternative to attenuate oxidative stress. In our in vivo studies, mice receiving the combination of 7.14 mg/kg of body weight/day AA and 10 mg/kg/day BZ10 (AA+BZ10) showed a reduction in parasitemia that was more effective than that with those receiving BZ or AA alone. The combined treatment was effective in decreasing intracellular ROS and lipid peroxidation in cardiac tissue. Histological and PCR analyzes showed that AA also reduced the cardiac parasitism. However, the greatest benefit was seen in AA+BZ10 group, since cardiac inflammation was significantly reduced. In addition, the combined therapy prevented the hepatic damage induced by the infection. Our findings suggest that AA combined with a low dose of BZ may improve the trypanocidal activity and attenuate the toxic effects of BZ. The decrease in oxidative damage and inflammation observed in mice treated with AA+BZ10 could result in increased cardioprotection.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ácido Ascórbico
/
Doença de Chagas
/
Nitroimidazóis
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil