Chronic indeterminate phase of Chagas’ disease: mitochondrial involvement in infection with two strains

Abstract

Chagasic cardiopathy has become one of the most frequent causes of heart failure and sudden death, as well as one of the most common causes of cardio-embolic stroke in Latin America. The myocyte response to oxidative stress involves the progression of cellular changes, primarily targeting the mitochondria and modifying therefore the energy supply. In this paper we analysed the effect of the infection of mice with 2 different strains of Trypanosoma cruzi (Tulahuen and SGO Z12) in the chronic indeterminate stage (75 days post-infection), upon the structure and function of cardiac mitochondria. The structural results showed that 83% of the mitochondria from the Tulahuen-infected mice presented an increase in their matrix and 91% of the mitochondria from the SGO Z12-infected group showed a reduction in their diameter (P < 0.05). When the Krebs cycle and mitochondrial respiratory chain functionality was analysed through the measurement of the citrate synthase and complexes I to IV activity, it showed that their activity was altered in all cases in a similar manner in both infected groups. In this paper we have demonstrated that the chronic indeterminate phase is not 'silent' and that cardiac mitochondria are clearly involved in the genesis and progression to the chronic chagasic cardiopathy when different factors alter the host-parasite equilibrium.

Early Detection of Chronic Asymptomatic Chagas Infection

“…However, a normal 12-lead ECG result indicates a favorable prognosis for a patient when compared to ECG-altered ones [ 30 ]. Although the subject could have a normal ECG, significant functional abnormalities in the chronic ICF was experimentally demonstrated [ 32 , 33 ]. Thus, searching for disease conduction disorders on ECG, several researchers used HRECG for asymptomatic chagasic identification of subjects.…”

Detrimental effects of malaria, toxoplasmosis, leishmaniosis and Chagas disease on cardiac and skeletal muscles

“…Previous work by Báez et al has provided building evidence that functional and structural alterations to mitochondria are responsible for chagasic cardiomyopathy (28)(29)(30). More recent studies from the same group have extended this effect to murine skeletal muscle, observing disruptions in citrate synthase activity and cellular respiration malfunction.…”

Analysis of mitochondrial enzymatic activity in blood lymphomonocyte fractions during infection with different Trypanosoma cruzi strains

“…Cells were suspended by gentle aspirations performed with the Pasteur pipette and then solutions were centrifuged twice at 60-100 x g for 10 min at 18-20 °C for later supernatant removal. Lymphocytes were then suspended in Hank medium (pH 7.4) and mitochondria were isolated as previously described [10][11][12][13] on days 35, 75 and 365 postinfection. Briefly, blood aliquots were homogenized in equal volumes of ice-cold 10 mM Hepes buffer, pH 7.2, containing 420 mM mannitol, 140 mM sucrose, 2 mM EGTA, and 2 mg/mL BSA (fatty acid free).…”

“…The enzymatic activity of the respiratory complexes I to IV (CI-CIV) and the citrate synthase was determined by spectrophotometric analysis [10][11][12][13][20][21][22] . The protein concentrations were determined by the Bradford method 19 .…”

“…The enzymes activities of citrate synthase and CI-CIV complexes of mitochondria obtained from the lymphomonocyte fraction of blood samples were determined 35 days post infection (acute phase), 75 (indeterminate phase), and 365 days post infection (chronic phase), as previously described [11][12][13] .…”