This study used a murine model of Chagas disease to investigate the isolated and combined impact of Trypanosoma cruzi infection and benznidazole (BZ) therapy on liver structure and function. Male C57BL/6 mice were challenged with T. cruzi and BZ for 15 days. Serum levels of cytokines and hepatic enzymes, liver oxidative stress, morphology, collagen, and glycogen content were monitored. Separately, T. cruzi infection and BZ treatment resulted in a pro-oxidant status and hepatic reactive damage. Concurrently, both T. cruzi infection and BZ treatment induced upregulation of antioxidant enzymes and pathological reorganization of the liver parenchyma and stroma. T. cruzi infection increased serum levels of Th1 cytokines, which were reduced by BZ in both infected and non-infected animals. BZ also induced functional organ damage, increasing serum levels of liver enzymes. When combined, T. cruzi infection and BZ therapy elicited intense hepatic reactive damage that was not compensated by antioxidant enzymatic reaction, subsequently culminating in more severe morphofunctional hepatic injury. Taken together, these findings indicate that during specific treatment of Chagas disease, hepatic pathology may be a result of an interaction between BZ metabolism and specific mechanisms activated during the natural course of T. cruzi infection, rather than an isolated toxic effect of BZ on liver structure and function.

Red meat consumption was cross-sectionally associated with the occurrence of central obesity, hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The content of saturated fatty acid from red meat consumption may be a factor that contributed to this relationship, while white meat consumption was not associated with metabolic syndrome and the assessed biomarkers.

cAlthough suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi. Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-␥], interleukin 4 [IL-4], and MIP1-␣), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

We compared the relevance of ibuprofen, vitamins C and E to control oxidative/nitrosative stress and heart disease in mice infected by Trypanosoma cruzi. Swiss mice were randomized into five groups: control, uninfected; infected without treatment; and infected treated with vitamins C, E or ibuprofen. Animals were inoculated with 2000 trypomastigote forms of T. cruzi. After 20 days, infected mice presented reduced vitamin C and E tissue levels, high cytokines (interferon gamma, tumour necrosis factor-α, interleukin 10 and chemokine ligand 2), prostaglandin F2α (PGF2α ) and nitric oxide (NO) cardiac production, intense myocarditis and reactive tissue damage, which was directly correlated with the intensity of the inflammatory infiltrate and the degree of pathological cardiac remodelling. Vitamins C and E supplementation were irrelevant to counteract reactive tissue damage and myocarditis in infected animals. Conversely, ibuprofen reduced tissue levels of cytokines, PGF2α and NO, as well as lipid and protein oxidation, antioxidant enzyme activity and the cardiac damage, without interfering with heart parasitism. Our results do not support the applicability of vitamin C and E supplementation in the management of acute Chagas cardiomyopathy. By controlling the inflammatory infiltrate, anti-inflammatory-based therapy proved to be a more rational strategy than a direct antioxidant therapy in attenuating oxidative/nitrosative stress and cardiac damage.