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Use of clomipramine as chemotherapy of the chronic phase of Chagas disease

Published online by Cambridge University Press:  27 March 2013

ROMINA FAURO ,
SILVINA LO PRESTI ,
CAROLINA BAZAN ,
ALEJANDRA BAEZ ,
MARIANA STRAUSS ,
FERNANDA TRIQUELL ,
DAVID CREMONEZZI ,
OLGA SANCHEZ NEGRETE ,
GASTON CAMINO WILLHUBER  and
PATRICIA PAGLINI-OLIVA
...Show all authors
ROMINA FAURO
Affiliation:
Cátedra de Parasitología y Micología Médicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, 5000 Córdoba, Argentina
SILVINA LO PRESTI
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina Cátedra de Metodología de la Investigación Científica, Escuela de Kinesiología y Fisioterapia, Facultad de Ciencias Médicas Universidad Nacional de Córdoba, Córdoba, Argentina Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
CAROLINA BAZAN
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
ALEJANDRA BAEZ
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
MARIANA STRAUSS
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
FERNANDA TRIQUELL
Affiliation:
Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
DAVID CREMONEZZI
Affiliation:
Cátedra de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
OLGA SANCHEZ NEGRETE
Affiliation:
Cátedra de Química Biológica, Facultad de Ciencias Exactas, Universidad Nacional de Salta, Salta, Argentina
GASTON CAMINO WILLHUBER
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
PATRICIA PAGLINI-OLIVA
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina
HECTOR WALTER RIVAROLA*
Affiliation:
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina Cátedra de Física Biomédica, Escuela de Medicina, Universidad Nacional de La Rioja, La Rioja, Argentina
*
*Corresponding author: Corrientes 3525, San Vicente, 5006 Córdoba, Argentina. Tel: +54 351 4566122. E-mail: [email protected].
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Summary

Chagas infection is a major endemic disease affecting Latin American countries. The persistence of Trypanosoma cruzi generates a chronic inflammatory reactivity that induces an immune response directed to the host's tissues. The effectiveness of the treatment in the chronic phase is still unsatisfactory due, amongst other reasons, to the collateral effects of the drugs used. We investigated the effect of clomipramine, a tricyclic antidepressant that, when used as a treatment of T. cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive and vital enzyme of T. cruzi. Clomipramine improved survival (P<0·05) by diminishing the parasite intensity as demonstrated by PCR studies in the heart and skeletal muscle, and significantly prevented the evolution to fibrosis of the inflammatory infiltrates. Clomipramine could be a good candidate for the treatment of chronic Chagas disease.

Keywords

Chagas diseasetreatmenttrypanothione reductaseclomipraminecardiac chronic stage
Type
Research Article
Information
Parasitology , Volume 140 , Issue 7 , June 2013 , pp. 917 - 927
Copyright
Copyright © Cambridge University Press 2013 

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References

REFERENCES

Amaral, L., Viveiros, M. and Kristiansen, J. E. (2001). Phenothiazines: potential alternatives for management of antibiotic resistant infections of tuberculosis and malaria in developing countries. Tropical Medicine and International Health 12, 1016–1022.CrossRefGoogle Scholar
Barbosa Marcon, G. E., Martins de Albuquerque, D., Martins Batista, A., Durante Andrade, P., Almeida, E. A., Guariento, M. E., Teixeira, M. A. B. and Botelho Costa, S. C. (2011). Trypanosoma cruzi: parasite persistence in tissues in chronic chagasic Brazilian patients. Memórias do Instituto Oswaldo Cruz 106, 85–91.CrossRefGoogle Scholar
Bazán, C., Lo Presti, M. S., Rivarola, H. W., Triquell, M. F., Fretes, R., Fernández, A. R., Enders, J. and Paglini-Oliva, P. (2008). Chemotherapy of chronic indeterminate Chagas disease ‘A novel approach to treatment’. Parasitology Research 103, 663–669.CrossRefGoogle ScholarPubMed
Benoist, C. and Mathis, D. (2001). Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? Nature Immunology 2, 797–801.CrossRefGoogle ScholarPubMed
Benson, T. J., McKie, J. H., Garforth, J., Borges, A., Fairlamb, A. H. and Douglas, K. T. (1992). Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochemical Journal 286, 9–11.CrossRefGoogle ScholarPubMed
Bonney, K. M. and Engman, D. M. (2008). Chagas heart disease pathogenesis: one mechanism or many? Current Molecular Medicine 8, 510–518.CrossRefGoogle ScholarPubMed
Bustamante, J. M., Rivarola, H. W., Fernandez, A. R., Enders, J. E., Fretes, R., Palma, J. A. and Paglini-Oliva, P. A. (2003). Indeterminate Chagas disease: Trypanosoma cruzi strain and reinfections are factors involved in the progression of cardiopathy. Clinical Science 104, 415–420.CrossRefGoogle ScholarPubMed
Bustamante, J. M., Lo Presti, M. S., Rivarola, H. W., Fernández, J. E., Enders, J. E., Fretes, R., Palma, J. A. and Paglini-Oliva, P. A. (2007). Treatment with benznidazole or thioridazine in the chronic phase of experimental Chagas disease improves cardiopathy. International Journal of Antimicrobial Agents 29, 733–739.CrossRefGoogle ScholarPubMed
Cançado, J. R. (1999). Criteria of Chagas disease cure. Memórias do Instituto Oswaldo Cruz 94, 331–335.CrossRefGoogle ScholarPubMed
Castro, J. (2006). Toxic side effects of drugs used to treat Chagas’ disease (American trypanosomiasis). Human and Experimental Toxicology 258, 471–479.CrossRefGoogle Scholar
De Castro, S. L. (1993). The challenge of Chagas’ disease chemotherapy: an update of drugs assayed against Trypanosoma cruzi. Acta Tropica 53, 83–98.CrossRefGoogle ScholarPubMed
De Souza, W. (2002). From the cell biology to the development of new chemotherapeutic approaches against trypanosomatids: dreams and reality. Kinetoplastid Biology and Disease 1, 3.CrossRefGoogle Scholar
Dias, J. C. P., Silveira, A. C. and Schofield, C. J. (2002). The impact of Chagas disease control in Latin America. Memórias do Instituto Oswaldo Cruz 97, 603–612.CrossRefGoogle ScholarPubMed
Elias, F. E., Vigliano, C. A., Laguens, R. P., Levin, M. J. and Berek, C. (2003). Analysis of the presence of Trypanosoma cruzi in the heart tissue of three patients with chronic Chagas’ heart disease. American Journal of Tropical Medicine and Hygiene 68, 242–247.CrossRefGoogle ScholarPubMed
Fabro, D. E., Velazquez, N., Mendoza, M., Streiger, E., Arias, S., Denner, M., Del Barco, N., Amicone, C., Pravia, N., Malagrino, A. and Ruiz, M. (2007). Evaluación de ELISA F29 como marcador de eficacia del tratamiento etiológico en la enfermedad de Chagas. Parasitología Latinoamericana 62, 103–111.Google Scholar
Gobbi, P., Lo Presti, M. S., Baez, A., Fernández, A. R., Enders, J. E., Fretes, R., Gea, S., Paglini-Oliva, P. A. and Rivarola, H. W. (2010). Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi. Parasitology Research 107, 1279–1283.CrossRefGoogle ScholarPubMed
Goijman, S. G. and Stoppani, A. O. M. (1985). Effects of nitroheterocyclic drugs on macromolecule synthesis and degradation in Trypanosoma cruzi. Biochemical Pharmacology 34, 1331–1336.CrossRefGoogle ScholarPubMed
Gonzalez, N. S. and Cazzulo, J. J. (1989). Effects of trypanosomicidal drugs on proteins biosynthesis in vitro and in vivo by Trypanosoma cruzi. Biochemical Pharmacology 38, 2873–2878.CrossRefGoogle Scholar
Gutierrez-Correa, J., Fairlamb, A. H. and Stoppani, A. O. (2001). Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals. Free Radical Research 34, 363–378.CrossRefGoogle ScholarPubMed
Hamond, D. J., Cover, B. and Gutteridge, W. E. (1984). A novel series of chemical structures active in vitro against the trypomastigote form of Trypanosoma cruzi. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 91–95.CrossRefGoogle Scholar
Higuchi, M., Benvenuti, L. A., Reis, M. M. and Metzger, M. (2003). Pathophysiology of the heart in Chagas’ disease: current status and new developments. Cardiovascular Research 60, 96–107.CrossRefGoogle ScholarPubMed
Jiménez Arce, G., Villalobos Quesada, M. J., Jiménez Montero, E. and Palma Platero, W. (2007). Determinación de la efectividad de cinco protocolos de extracción de ADN a partir de material parafinado para estudios moleculares. Revista Médica Universitaria Costa Rica 1, 1–10.Google Scholar
Jones, D. C., Ariza, A., Chowb, W. A., Oza, L. S. and Fairlamb, A. H. (2010). Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi. Molecular and Biochemical Parasitology 169, 12–19.CrossRefGoogle ScholarPubMed
Khan, M. and Omar, F. (2007). Trypanothione reductase: a viable chemotherapeutic target for antitrypanosomal and antileishmanial drug design. Drug Target Insights 2, 129–146.CrossRefGoogle ScholarPubMed
Kirchhoff, F., Hofer, H. W. and Schachner, M. J. (1993). Myelin-associated glycoprotein is phosphorylated by protein kinase. Neuroscience 36, 368–381.Google ScholarPubMed
Krauth-Siegel, R. L. and Comini, M. A. (2008). Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochimica et Biophysica Acta 1780, 1236–1248.CrossRefGoogle ScholarPubMed
Markvardsen, P., Bjerke, T., Rüdiger, N., Schiøtz, P. O., Gregersen, N., Justesen, J. and Paludan, K. (1995). A polymerase chain reaction-based method for the semiquantitative study of interleukin-8 mRNA in human basophil leukocytes. Scandinavian Journal of Clinical and Laboratory Investigation 55, 487–493.CrossRefGoogle ScholarPubMed
Marr, J. J. and Docampo, R. (1986). Chemotherapy for Chagas’ disease: a perspective of current therapy and considerations for future research. Reviews of Infectious Diseases 8, 884.CrossRefGoogle ScholarPubMed
Miles, M. A., Toye, P. J., Oswald, S. C. and Godfrey, D. C. (1977). The identification by isoenzyme patterns of two distinct strain groups of Trypanosoma cruzi, circulating independently in a rural area of Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene 71, 217–225.CrossRefGoogle Scholar
Moncayo, A. (1999). Progreso en la interrupción de la transmisión de la Enfermedad de Chagas en los países del cono sur. MEDICINA (Buenos Aires) 59, 120–124.Google Scholar
Montes De Oca, M., Torres, S. H., Finol, H. J., Loyo, J. G., Vásquez, F. N., Hernández, N. and Anchústegui, B. (2007). Alteraciones musculares periféricas en la enfermedad de Chagas. Gaceta Médica de Caracas 115, 55–61.Google Scholar
Morello, A. (1988). The biochemistry of the mode of action of drugs and the detoxication mechanism in Trypanosoma cruzi. Comparative Physiology and Biochemistry 90, 1–12.Google ScholarPubMed
Moser, D. R., Kirchhoff, L. V. and Donelson, C. (1989). Detection of Trypanosoma cruzi by DNA amplification using polymerase chain reaction. Journal of Clinical Microbiology 27, 1477–1482.CrossRefGoogle ScholarPubMed
Murta, S. M. F., Krieger, M. A., Montenegro, L. R., Campos, F. F., Probst, C. M., Ávila, A. R., Muto, N. H., De Oliveira, R. C., Nunes, L. R., Nirdé, P., Bruna-Romero, O., Goldenberg, S. and Romanha, A. J. (2006). Deletion of copies of the gene encoding old yellow enzyme (TcOYE), a NAD(P)H flavin oxidoreductase, associates with in vitro-induced benznidazole resistance in Trypanosoma cruzi. Molecular and Biochemical Parasitology 146, 151–162.CrossRefGoogle ScholarPubMed
Paglini-Oliva, P., Fernández, A. R. and Lacuara, J. L. (1987). Pharmacological and contractile response of myocardium of chagasic Albino Swiss mice. Acta Physiologica et Pharmacologica Latinoamericana 37, 395–401.Google ScholarPubMed
Paglini-Oliva, P. A. and Rivarola, H. W. (2003). Central nervous system agents used as Trypanosoma cruzi infection chemotherapy: phenothiazines and related compounds. Current Medicinal Chemistry – Anti-Infective Agents 2, 323–332.CrossRefGoogle Scholar
Postan, M., Arnaiz, M. R. and Fichera, L. E. (1999). Respuesta de las células musculares cardíacas a la infección con Trypanosoma cruzi. Medicina (Buenos Aires) 59, 57–62.Google Scholar
Rivarola, H. W., Fernández, A. R., Enders, J. E., Fretes, R., Gea, S. and Paglini-Oliva, P. (2001). Effects of clomipramine on Trypanosoma cruzi infection in mice. Royal Society of Tropical Medicine and Hygiene 95, 1–5.CrossRefGoogle ScholarPubMed
Rivarola, H. W. and Paglini-Oliva, P. A. (2002). Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas’ disease evolution. Current Drug Targets – Cardiovascular and Hematological Disorders 2, 43–52.CrossRefGoogle ScholarPubMed
Rivarola, H. W., Bustamante, J. M., Lo Presti, M. S., Fernández, A. R., Enders, J. E., Fretes, R. E., Gea, S. and Paglini-Oliva, P. A. (2005). Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area. Experimental Parasitology 111, 80–86.CrossRefGoogle ScholarPubMed
Rodrígues Coura, J. and de Castro, S. (2002). A critical review on Chagas disease chemotherapy. Memórias do Instituto Oswaldo Cruz 97, 3–24.CrossRefGoogle Scholar
Rossmanith, W. G., Hoffmeister, U., Wolfahrt, S., Kleine, B., McLean, M., Jacobs, R. A. and Grossman, A. B. (1999). Expression and functional analysis of endothelial nitric oxide synthase (eNOS) in human placenta. Molecular Human Reproduction 5, 487–494.CrossRefGoogle ScholarPubMed
Roufogalis, B. D., Minocherhomjee, A. M. and Al-Jobore, A. (1983). Pharmacological antagonism of calmodulin. Canadian Journal of Biochemistry and Cell Biology 61, 927–933.CrossRefGoogle ScholarPubMed
Sánchez Negrette, O., Sánchez Valdéz, F. J., Lacunza, C. D., GarcíaBustos, M. F., Mora, M. C., Uncos, A. D. and Basombrío, M. A. (2008). Serological evaluation of specific-antibody levels in patients treated for chronic. Clinical and Vaccine Immunology 15, 297–302.CrossRefGoogle ScholarPubMed
Schmunis, G. A. (2007). Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Memórias do Instituto Oswaldo Cruz 102, 75–85.CrossRefGoogle ScholarPubMed
Segura, M. A., Barberá, L. C., Ramos, F. and Basombrio, M. A. (1996). Regression of antibodies and resistance to reinfection in mice inoculated with an attenuated Trypanosoma cruzi strain and treated with nifurtimox. Memórias do Instituto Oswaldo Cruz 91, 316.Google Scholar
Sosa Estani, S. and Segura, E. L. (1999). Treatment of Trypanosoma cruzi infection in the undetermined phase. Experience and current guidelines of treatment in Argentina. Memórias do Instituto Oswaldo Cruz 94, 363–365.CrossRefGoogle ScholarPubMed
Sosa-Estani, S., Viotti, R. and Segura, E. L. (2009). Therapy, diagnosis and prognosis of chronic Chagas disease: insight gained in Argentina. Memórias do Instituto Oswaldo Cruz 104, 167–180.CrossRefGoogle ScholarPubMed
Suasnábar, D. F., Arias, E. and Streiger, M. (2000). Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic Chagasic patients. Revista Instituto Medicina Tropical São Paulo 42, 99–110.CrossRefGoogle Scholar
Tarleton, R. L. (2001). Parasite persistence in the aetiology of Chagas disease. International Journal of Parasitology 31, 549–553.CrossRefGoogle ScholarPubMed
Tovar, J., Cunningham, M. L., Smith, C., Croft, S. L. and Fairlamb, A. H. (1998). Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival. Proceedings of the National Academy of Sciences USA 95, 5311–5316.CrossRefGoogle ScholarPubMed
Urbina, J. A. (2002). Chemotherapy of Chagas disease. Current Pharmaceutical Design 8, 287–295.CrossRefGoogle ScholarPubMed
Wilkinson, S. R., Taylor, M. C., Horn, D., Kelly, J. M. and Cheeseman, I. (2008). A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proceedings of the National Academy of Sciences USA 105, 5022–5027.CrossRefGoogle ScholarPubMed
World Health Organization (2010). WHO Report on Chagas Disease. World Health Organization on behalf of the Special Programme for Research and Training in Tropical Diseases.Google Scholar
Zhang, L. R. and Tarleton, L. (1999). Parasite persistence correlates with disease severity and localization in chronic Chagas’ disease. Journal of Infectious Diseases 180, 480–486.CrossRefGoogle ScholarPubMed