Chagas Cardiomyopathy; Adenosine Desaminase/drug effects; Antioxidants; Drug-Related Side Effects and Adverses Reactions
Dear Editor,
Evidence suggests that approximately 12 million individuals in Latin America are infected
with Trypanosoma cruzi and present Chagas disease11 Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic
Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54,. Even though the disease was described more than 100 years ago,
chemotherapy directed against its etiological agent is restricted to two compounds which
are only effective in the acute phase of the disease11 Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic
Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54,, benznidazole and nifurtimox. Within this context, chronic Chagas heart
disease (CHCD) lacks immunopharmacological studies, given that its pathogenesis involves an
imbalance in the host's immune system. In the chronic phase, CHCD is associated with
increased oxidative stress with intense and extensive inflammation and fibrosis in the
myocardium, with consequent autonomic dysfunction and production of antibodies directed to
the myocytes, beta adrenergic receptors, and neurons11 Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic
Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54,
2 Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto
AS, et al. A randomized trial of carvedilol after renin-angiotensin system inhibition
in chronic Chagas cardiomyopathy. Am Heart J. 2007;153(4):544-8.-33 Budni P, Pedrosa RC, Garlet TR, Dalmarco EM, Lino MR, Simionato EL, et
al. Carvedilol attenuates oxidative stress in chronic Chagasic cardiomyopathy. Arq
Bras Cardiol. 2012;98(3):218-24.. Rocha et al11 Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic
Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54, demonstrate in their study that patients who develop
CHCD present increased levels of TNF-alpha and CCL-2 when compared with individuals with
the indeterminate form of Chagas disease11 Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic
Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54,. A
parallel then may be drawn with studies conducted by Yue et al. who reported that the
production of superoxide anions occurs from activation of the NADPH system promoted by
proinflammatory cytokines, in particular, TNF-alpha44 Yue TL, Cheng HY, Lysko PG, McKenna PJ, Feuerstein R, Gu JL, et al.
Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and
free radical scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8.. In fact, studies suggest that the antioxidant effects of carvedilol are very
effective in the treatment of patients with CHCD. In addition to that, the presence of
carbazole groups and hydroxylated metabolites in the molecular structure confers to
carvedilol a high antioxidant activity22 Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto
AS, et al. A randomized trial of carvedilol after renin-angiotensin system inhibition
in chronic Chagas cardiomyopathy. Am Heart J. 2007;153(4):544-8.,33 Budni P, Pedrosa RC, Garlet TR, Dalmarco EM, Lino MR, Simionato EL, et
al. Carvedilol attenuates oxidative stress in chronic Chagasic cardiomyopathy. Arq
Bras Cardiol. 2012;98(3):218-24.. Studies highlight the
ability of carvedilol to act as a transition metal when donating electrons to reactive
oxygen species (ROS) and reactive nitrogen species (RNS) in an attempt to neutralize the
effects of oxidative damage caused by T. cruzi in the acute phase, which
persist until the chronic phase44 Yue TL, Cheng HY, Lysko PG, McKenna PJ, Feuerstein R, Gu JL, et al.
Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and
free radical scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8.. Budni et al33 Budni P, Pedrosa RC, Garlet TR, Dalmarco EM, Lino MR, Simionato EL, et
al. Carvedilol attenuates oxidative stress in chronic Chagasic cardiomyopathy. Arq
Bras Cardiol. 2012;98(3):218-24. in their study confirm this hypothesis showing that
before a therapeutic intervention with carvedilol, patients with cardiac involvement showed
high levels of oxidative markers, whereas patients who received an intervention with
carvedilol showed increased levels of nitric oxide (NO) and adenosine deaminase (ADA),
important supporting elements in oxidative defense and improvement of immune response33 Budni P, Pedrosa RC, Garlet TR, Dalmarco EM, Lino MR, Simionato EL, et
al. Carvedilol attenuates oxidative stress in chronic Chagasic cardiomyopathy. Arq
Bras Cardiol. 2012;98(3):218-24.,44 Yue TL, Cheng HY, Lysko PG, McKenna PJ, Feuerstein R, Gu JL, et al.
Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and
free radical scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8..
Therefore, studies are needed to identify treatments able to prevent cardiac damage caused
by this infection and to offer tools to improve survival and provide a better quality of
life to affected individuals.
References
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1Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic Chagas cardiomyopathy. Front Biosci. 2003;8(1):44-54,
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2Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto AS, et al. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J. 2007;153(4):544-8.
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3Budni P, Pedrosa RC, Garlet TR, Dalmarco EM, Lino MR, Simionato EL, et al. Carvedilol attenuates oxidative stress in chronic Chagasic cardiomyopathy. Arq Bras Cardiol. 2012;98(3):218-24.
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4Yue TL, Cheng HY, Lysko PG, McKenna PJ, Feuerstein R, Gu JL, et al. Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8.
Publication Dates
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Publication in this collection
Oct 2014
History
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Received
20 June 2014 -
Reviewed
15 Aug 2014 -
Accepted
15 Aug 2014