Mitigation of benznidazole toxicity and oxidative stress following ascorbic acid supplementation in an adult traveller with chronic indeterminate Chagas’ disease

Abstract

Background Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas’ disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment. Objectives We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity. Methods We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000 mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation. Results AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient. Conclusions We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage.