Evaluation of antioxidant therapy in experimental Chagas disease

Abstract

Introduction: Stimulation of inflammatory mediators such as cytokines and chemokines may cause oxidative stress in Chagas disease. In this study, we evaluated the merit of vitamins C and E as antioxidant therapy to minimize the oxidative stress-induced damage in an experimental model of Chagas disease. Methods: Ninety-six Swiss mice were infected with Trypanosoma cruzi QM2 and treated with vitamins C, E, or both (C/E) for 60 and 120 days, and their effects compared to placebo administration were evaluated in the acute and chronic disease phases. Results: There was no difference in parasitemia among treatment groups. However, histological analysis showed more severe inflammation in the skeletal muscle in the vitamin supplementation groups at both the acute and chronic phases. Biochemical analyses during the acute phase showed increased ferric-reducing ability of plasma (FRAP) and glutathione (GSH) levels in the vitamin C and C/E groups. In the chronic phase, a decrease in GSH levels was observed in the vitamin E group and a decrease in thiobarbituric acid reactive substances (TBARS) was observed in the vitamin C/E group. Moreover, there was a decrease in TBARS in the cardiac tissues of the vitamin C and C/E groups compared to that of the placebo group, although this level was greater in the vitamin E group than in the vitamin C group. Conclusions: The antioxidant action of vitamins C and E reduced oxidative stress in both the acute and chronic phases of Chagas disease, with a marked effect from joint administration, indicating their inherent synergism.

Potential Role of Antioxidants as Adjunctive Therapy in Chagas Disease

“…In contrast, treatment with vitE only had a prooxidant effect evidenced by an increase in lipid peroxidation in the skeletal muscle of acutely infected mice and no antioxidant effect in chronic Chagas mice. In another study, Novaes et al [48] used a similar vitE dose as reported by Tieghi et al [53] and showed reduction in lipid peroxidation in the cardiac muscle of vitE-treated infected mice, though these authors also noted no increase in the antioxidant enzyme activities. Others showed that vitC had a prooxidant effect 3 Oxidative Medicine and Cellular Longevity Heart, heart mitochondria Cv: carvedilol; SOD: superoxide dismutase; CAT: catalase; MDA: malondialdehyde; GSH: glutathione; GST: glutathione S-transferase; FRAP: plasma antioxidant capacity; TBARS: thiobarbituric acid reactive substances; PCN: protein carbonyl levels; PBN: phenyl-alfa-tert-butyl nitrone; B100: 100 mg/kg of body weight benznidazole; B50: 50 mg/kg benznidazole; C100: 100 mg/kg curcumin; dpi: days postinfection.…”

“…The number of parasites used for challenge infection was variable, ranging from 1 × 10 1 to 1 × 10 5 blood trypomastigotes, that was mostly related to virulence of the parasite isolates but unrelated to the development of the acute or chronic phase. The antioxidant compounds used in these studies included phenyl-α-tert-butyl nitrone (PBN) [50,51], carvedilol, vitamin E (vitE) and/or vitamin C (vitC) [52,53], melatonin [54], curcumin [55], resveratrol, and astaxanthin [56]. Vitamin C was the most commonly used antioxidant, evalu-ated in five of the published studies.…”

“…Tieghi et al evaluated the effect of vitC and vitE (individually and in combination) in acutely and chronically infected Swiss mice [53]. The authors noted that supplementation with vitC, vitE, or both had no effect on parasitemia levels.…”

Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review

“…Vitamin C/E treated group showed a reduction of TBARS. The antioxidant action of vitamins C and E reduced oxidative stress in the acute and chronic phases of Chagas disease with a marked effect following co-administration, indicating inherent synergism (Tieghi et al ., 2017).…”

Purinergic Antagonist Suramin Aggravates Myocarditis and Increases Mortality by Enhancing Parasitism, Inflammation, and Reactive Tissue Damage in Trypanosoma cruzi‐Infected Mice

“…Unlike acute infections, chronic Chagas disease is often associated with the downregulation of antioxidant enzymes. This process seems to be related to the enzymatic exhaustion created by sustained oxidative stress, which is closely related to the severity of chronic Chagas cardiomyopathy [ 26 , 67 ].…”