Benefits of Ascorbic Acid in Association with Low-Dose Benznidazole in Treatment of Chagas Disease

Author(s)

Providello, Maiara Voltarelli ^[1] ; Carneiro, Zumira Aparecida ^[1] ; Portapilla, Gisele Bulhoes ^[1] ; do Vale, Gabriel Tavares ^[2] ; Camargo, Ricardo Souza ^[3] ; Tirapelli, Carlos Renato ^[4] ; de Albuquerque, Sergio ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Sch Nursing, Dept Psychiat Nursing & Human Sci, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Antimicrobial Agents and Chemotherapy; v. 62, n. 9 SEP 2018.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 16/03632-6 - Determining the therapeutic potential of natural antioxidants in the experimental Chagas disease
• Grantee: Maiara Voltarelli Providello
• Support Opportunities: Scholarships in Brazil - Master