Immunopharmacological Approach of Carvedilol in Chronic Chagas Heart Disease

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 disease¹. 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 disease¹, 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 neurons^1-3. Rocha et al¹ 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 disease¹. 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-alpha⁴. 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 activity^2,3. 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 phase⁴. Budni et al³ 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 response^3,4. 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

• ¹
  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.
• ³
  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.
• ⁴
  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.

Publication Dates

• Publication in this collection
  Oct 2014

History

• Received
  20 June 2014
• Reviewed
  15 Aug 2014
• Accepted
  15 Aug 2014