ROLE OF ASCORBIC ACID AS SUPPORTING IN THE THERAPEUTIC OF CHAGAS DISEASE: BENEFITS IN THE ASSOCIATION WITH LOW DOSE OF BENZNIDAZOLE [PublishAheadOfPrint]

The acute phase of Chagas disease (CD) is characterized by high parasitic proliferation and intense inflammation, exacerbating the generation of reactive oxygen and nitrogen species (ROS and RNS, respectively). 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, as ascorbic acid (AA), would be a valid alternative to attenuate oxidative stress. In our in vivo studies, mice receiving the combination AA(7.14mg/kg/day)+BZ10(10mg/kg/day) showed a reduction in parasitemia more effective than 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 associated 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.

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