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

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.

Can Biomarkers of Oxidative Stress in Serum Predict Disease Severity in West Nile Virus Infection? A Pilot Study.

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.