Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

Silva, Diana Rodrigues da; Castro, Solange L. de; Alves, Monique Castro da Silva; Batista, Wanderson Silva; Oliveira, Gabriel Melo de

doi:10.1590/s0074-02762012000200010

Cited by 16 publications

(15 citation statements)

References 40 publications

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“…In our murine model, the physical changes corresponding to the chronic phase appeared after day 45, which correlated with absence of circulating parasites. These physical characteristics are consistent with other murine models, featuring alterations in fur colour with piloerection, hunched posture and severe paralysis of the lower extremities (da Silva et al 2012). Kinetics of parasitaemia in this model also showed similar levels to other well-studied strains in chronic phase (Table I), such as T. cruzi Tulahuén, 21SF, Mambai, Bolivia, TBAR/MX/0000/Queretaro and MHOM/MX/1994/Ninoa (Andrade & Grimaud 1986, Petray et al 1995, Espinoza et al 2010).…”

Section: Discussionsupporting

confidence: 89%

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

González-Mejia

Torres‐Rasgado

Porchia

et al. 2014

Mem. Inst. Oswaldo Cruz

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Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

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Section: Discussionsupporting

confidence: 89%

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

González-Mejia

Torres‐Rasgado

Porchia

et al. 2014

Mem. Inst. Oswaldo Cruz

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“…Food and water consumption were measured daily (beginning one week prior to the infection) by calculating the differences between the weight/volume offered (250 g/250 mL) and the amounts left in each cage after 24 h. The individual consumption amounts were estimated using previously reported formulae. (18) Motor and exploratory activity studies -To analyse the spontaneous activity of individual mice, each animal was monitored by the video-tracking tool NoldusEtho-VisionXT6 (Noldus Information Technology, Leesburg, Netherlands). The arena was defined as twelve rectangles that were divided into lateral and central areas and calibrated to contain equal areas to ensure the consistency of the parameters.…”

Section: Methodsmentioning

confidence: 99%

Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection

Cascabulho

Meuser-Batista

Moura

et al. 2020

Mem. Inst. Oswaldo Cruz

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BACKGROUND Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active in vitro. OBJECTIVES In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated. METHODS in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses. FINDINGS Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters. MAIN CONCLUSION N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.

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“…This analysis measured the following parameters at different times: (i) locomotor activity, i.e., covered distance (m) and average velocity (cm/s); and (ii) exploratory activity, the frequency of travel to the central region (number of events) every 5 min and the time spent in this region (seconds). The different groups were compared using the Student’s t-test with the results considered statistically significant at p ≤ 0.05 [44]. The tests were performed twice for control groups (neither bled nor injected), AWB 20 μL and saline 20 μL analysis ( n = 10 each group).…”

Section: Methodsmentioning

confidence: 99%

“…In the assays performed on healthy animals, at the each endpoint, the heart, spleen, liver and kidneys were collected and their respective weights measured [44]. In all assays, the different groups were compared using analysis of variance (ANOVA) and the results considered statistically significant when p ≤ 0.05.…”

Section: Methodsmentioning

confidence: 99%

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

Pavão

Demarque

Batista

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundAutologous whole blood (AWB) administration is described as alternative/complementary medical practice widely employed in medical and veterinary therapy against infections, chronic pathologies and neoplasias. Our aim is to investigate in vivo biological effect of AWB using healthy murine models under the course of Trypanosoma cruzi acute infection.MethodsThe first set of studies consisted of injecting different volumes of AWB and saline (SAL) into the posterior region of quadriceps muscle of healthy male Swiss mice under distinct therapeutic schemes evaluating: animal behavior, body and organ weight, hemogram, plasmatic biochemical markers for tissue damage and inflammatory cytokine levels and profile. To assess the impact on the experimental T. cruzi infection, different schemes (prior and post infection) and periods of AWB administration (from one up to 10 days) were conducted, also employing heterologous whole blood (HWB) and evaluating plasma cytokine profile.ResultsNo major adverse events were observed in healthy AWB-treated mice, except gait impairment in animals that received three doses of 20 μL AWB in the same hind limb. AWB and SAL triggered an immediate polymorphonuclear response followed by mononuclear infiltrate. Although SAL triggered an inflammatory response, the kinetics and intensity of the histological profile and humoral mediator levels were different from AWB, the latter occurring earlier and more intensely with concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly composed of mononuclear cells with IL-10, was increased at 24 h. According to the mouse model of acute T. cruzi infection, only minor decreases (< 30%) in the parasitemia levels were produced by AWB and HWB given before and after infection, without protecting against mortality. Rises in IFN-gamma, TNF-alpha and IL-6 were detected at 9 dpi in all infected animals as compared to uninfected mice but only Bz displayed a statistically significant diminution (p = 0.02) in TNF-alpha levels than infected and untreated mice.ConclusionsThis study revealed that the use of autologous whole blood (AWB) in the acute model employed was unable to reduce the parasitic load of infected mice, providing only a minor decrease in parasitemia levels (up to 30%) but without protecting against animal mortality. Further in vivo studies will be necessary to elucidate the effective impact of this procedure.

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Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

Cited by 16 publications

References 40 publications

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

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