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Cordycepin (3′-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected with Trypanosoma evansi

Published online by Cambridge University Press:  29 January 2013

LUCIANA DALLA ROSA ,
ALEKSANDRO S. DA SILVA ,
LUCAS T. GRESSLER ,
CAMILA B. OLIVEIRA ,
MARIA G. C. DAMBRÓS ,
LUIZ C. MILETTI ,
RAQUELI T. FRANÇA ,
SONIA T. A. LOPES ,
YASMIN N. SAMARA  and
MARCELO L. DA VEIGA
...Show all authors
LUCIANA DALLA ROSA*
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil
ALEKSANDRO S. DA SILVA
Affiliation:
Department of Animal Science, Universidade do Estado de Santa Catarina, Chapecó, SC, Brazil
LUCAS T. GRESSLER
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil
CAMILA B. OLIVEIRA
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil
MARIA G. C. DAMBRÓS
Affiliation:
Department of Animal Production, Universidade do Estado de Santa Catarina, Lages, SC, Brazil
LUIZ C. MILETTI
Affiliation:
Department of Animal Production, Universidade do Estado de Santa Catarina, Lages, SC, Brazil
RAQUELI T. FRANÇA
Affiliation:
Department of Small Animals, Universidade Federal de Santa Maria, Brazil
SONIA T. A. LOPES
Affiliation:
Department of Small Animals, Universidade Federal de Santa Maria, Brazil
YASMIN N. SAMARA
Affiliation:
Department of Morphology, Universidade Federal de Santa Maria, Brazil
MARCELO L. DA VEIGA
Affiliation:
Department of Morphology, Universidade Federal de Santa Maria, Brazil
SILVIA G. MONTEIRO
Affiliation:
Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil
*
*Corresponding author: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil. E-mail: [email protected]
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Summary

The aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3′-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase) in vitro by using mice experimentally infected with Trypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In the in vivo trials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg−1) and pentostatin (2 mg kg−1) was 100% effective in the T. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3′-deoxyadenosine with deoxycoformycin has a curative effect on mice infected with T. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.

Keywords

trypanosomiasisadenosineadenosine deaminase inhibitor
Type
Research Article
Information
Parasitology , Volume 140 , Issue 5 , April 2013 , pp. 663 - 671
Copyright
Copyright © Cambridge University Press 2013

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References

REFERENCES

Adamson, R. H., Zaharevitz, D. W. and Johns, D. G. (1977). Enhancement of the biological activity of adenosine analogs by the adenosine deaminase inhibitor 2-deoxycoformycin. Pharmacology 15, 84–89.Google Scholar
Agarwal, R. P., Sagar, S. M. and Parks, R. E. Jr. (1975). Adenosine deaminase from human erythrocytes: purification and effects of adenosine analogs. Biochemical Pharmacology 24, 693–701.Google Scholar
Aiyedun, B. A., Williamson, J. and Amodu, A. A. (1973). The effect of cordycepin on tsetse-borne Trypanosoma vivax infections. Acta Tropica 30, 276–278.Google ScholarPubMed
Baltz, T., Baltz, D., Giroud, C. and Crockett, J. (1985). Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense . EMBO Journal 4, 1273–1277.Google Scholar
Bzowska, A., Lassota, P. and Shugar, D. (1985). Phosphorylation of coformycin and 2′-deoxycoformycin, and substrate and inhibitor properties of the nucleosides and nucleotides in several enzyme systems. Zeitschrift für Naturforschung, Section C: Biosciences 40, 710–714.Google Scholar
Colpo, C. B., Monteiro, S. G. and Stainki, D. R. (2005). Natural infection by Trypanosoma evansi in dogs. Ciência Rural 35, 717–719.Google Scholar
Da Silva, A. S., Bellé, L. P., Bitencourt, P. E. R., Souza, V. C. G., Costa, M. M., Oliveira, C. B., Jaques, J. A., Leal, D. B. R., Moretto, M. B., Mazzanti, C. M., Lopes, S. T. A. and Monteiro, S. G. (2011 b). Activity of the enzyme adenosine deaminase in serum, erythrocytes and lymphocytes of rats infected with Trypanosoma evansi . Parasitology, 138, 201–208.CrossRefGoogle ScholarPubMed
Da Silva, A. S., Doyle, R. L. and Monteiro, S. G. (2006). Método de contenção e confecção de esfregaço sanguíneo para pesquisa de hemoparasitas em ratos e camundongos. Revista da FZVA 13, 83–87.Google Scholar
Da Silva, A. S., Tochetto, C., Zanette, R. A., Pierezan, F., Rissi, D. R., Santurio, J. M. and Monteiro, S. G. (2008). Aceturato de diminazeno e dipropionato de imidocarb no controle de infecção por Trypanosoma evansi em Rattus norvegicus infectados experimentalmente. Ciência Rural 38, 1357–1362.Google Scholar
Da Silva, A. S., Wolkmer, P., Nunes, J. T. S., Duck, M. R. K., Oliveira, C. B., Gressler, L. T., Costa, M. M., Zanette, R. A., Mazzanti, C. M., Lopes, S. T. A. and Monteiro, S. G. (2011 a). Susceptibility of Trypanosoma evansi to cordycepin. Biomedicine & Pharmacotherapy 65, 220–223.CrossRefGoogle ScholarPubMed
Dobson, R. J., Dargantes, A. P., Mercado, R. T. and Reid, S. A. (2009). Models for Trypanosoma evansi (surra), its control and economic impact on small-hold livestock owners in the Philippines. International Journal for Parasitology 39, 1115–1123.Google Scholar
Franco, R., Casado, V., Ciruela, F., Saura, C., Mallol, J., Canela, E. I. and Louis, C. (1997). Cell surface adenosine deaminase: much more than an ectoenzyme. Progress of Neurobiology 52, 283–294.Google Scholar
Greiger, J. D. and Nagy, J. I. (1986). Distribution of adenosine deaminase activity in rat brain and spinal cord. Journal of Neuroscience 6, 2707–2714.CrossRefGoogle Scholar
Hammond, D. J. and Gutteridge, W. E. (1984). Purine and pyrimidine metabolism in the trypanosomatidae. Molecular and Biochemical Parasitology 13, 243–261.Google Scholar
Hassan, H. F. and Coombs, G. H. (1988). Purine and pyrimidine metabolism in parasitic protozoa. FEMS Microbiology Reviews 4, 47–83.Google Scholar
Hoare, C. A. (1972). The Trypanosomes of Mammals: a Zoological Monograph. Blackwell, Oxford, UK.Google Scholar
James, D. M. and Born, G. V. (1980). Uptake of purine bases and nucleosides in African trypanosomes. Parasitology 81, 383–393.CrossRefGoogle ScholarPubMed
Jennings, F. W., Whitelaw, D. D. and Urquhart, G. M. (1977). The relationship between duration of infection with T. brucei in mice and the efficacy of chemotherapy. Parasitology 75, 145–153.Google Scholar
Koning, H. P., Anderson, L. F., Stewart, M., Burchmore, R. J., Wallace, L. J., Barrett, M. P. (2004). The trypanocide diminazene aceturate is accumulated predominantly through the TbAT1 purine transporter: additional insights on diamidine resistance in African trypanosomes. Antimicrobial Agents and Chemotherapy 48, 1515–1519.CrossRefGoogle ScholarPubMed
Luckins, A. G. and Dwinger, R. H. (2004). Non-tsetse-transmitted animal trypanosomiasis. In The Trypanosomiases (ed. Maudlin, I., Holmes, P. H. and Miles, M. A.), pp. 269–281. CABI Publishing, Wallingford, Oxon., UK.Google Scholar
Major, P. P., Agarwal, R. P. and Kufe, D. W. (1981). Clinical pharmacology of deoxycoformycin. Blood 58, 91–96.Google Scholar
Maser, P., Sutterlin, C., Kralli, A. and Kaminsky, R. (1999). A nucleoside transporter from Trypanosoma brucei involved in drug resistance. Science 285, 242–244.Google Scholar
Maser, P., Vogel, D., Schmid, C., Raz, B. and Kaminsky, R. (2001). Identification and characterization of trypanocides by functional expression of an adenosine transporter from Trypanosoma brucei in yeast. Journal of Molecular Medicine 79, 121–127.Google Scholar
Maudlin, I., Holmes, P. and Miles, M. A. (2004). The Trypanosomiases. CABI Publishing, Wallingford, Oxon, UK.Google Scholar
McConnell, W. R., Suling, W. I., Rice, L. S., Shannon, W. M. and Hill, D. L. (1978). Use of microbiologic and enzymatic assays in studies on the disposition of 2′-deoxycoformycin in the mouse. Cancer Treatment Reports 62, 1153–1154.Google Scholar
Peregrine, A. S. and Mamman, M. (1993). Pharmacology of diminazene: a review. Acta Tropica 54, 185–203.Google Scholar
Powar, R. M., Shegokar, V. R., Joshi, P. P., Dani, V. S., Tankhiwale, N. S., Truc, P., Jannin, J. and Bhargava, A. (2006). A rare case of human trypanosomiasis caused by Trypanosoma evansi . Indian Journal of Medical Microbiology 24, 72–74.Google Scholar
Rodman, L. E., Farnell, D. R., Coyne, J. M., Allan, P. W., Hill, D. L., Duncan, K. L. K., Tomaszewski, J. E., Smith, A. C. and Page, J. G. (1997). Toxicity of cordycepin in combination with the adenosine deaminase inhibitor 2′ deoxycoformycin in beagle dogs. Toxicology and Applied Pharmacology 147, 39–45.CrossRefGoogle ScholarPubMed
Rottenberg, M. E., Masocha, W., Ferella, M., Petitto-Assis, F., Goto, H., Kristensson, K., McCaffrey, R. and Wigzell, H. (2005). Treatment of African trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model. Journal of Infectious Diseases 192, 1658–1665.Google Scholar
Santos, V. M. R., Donnici, C. L., Dacosta, J. B. N. and Caixeiro, J. M. R. (2007). Compostos organofosforados pentavalentes: histórico, métodos sintéticos de preparação e aplicações como inseticidas e agentes antitumorais. Química Nova 30, 159–170.Google Scholar
Sirivan, C., Pramoolsinsap, T. and Pemayodhin, P. (1994). Effect of diminazene aceturate and isometamidium chloride on the control of Trypanosoma evansi in naturally infected sow. Health Science Journals in Thailand 8, 101–109.Google Scholar
Spinosa, H. S., Górniak, S. L. and Bernardi, M. M. (1999). Farmacologia Aplicada à Medicina Veterinária. Guanabara Koogan, Rio de Janeiro, Brasil.Google Scholar
Tuntasuvan, D., Jarabrum, W., Viseshakul, N., Mohkaew, K., Borisutsuwan, S., Theeraphan, A. and Kongkanjana, N. (2003). Chemotherapy of surra in horses and mules with diminazene aceturate. Veterinary Parasitology 110, 227–233.Google Scholar
Ventura, R. M., Takeda, G. F., Silva, R. A. M. S., Nunes, V. L. B., Buck, G. A. and Teixeira, M. M. G. (2002). Genetic relatedness among Trypanosoma evansi stocks by random amplification of polymorphic DNA and evaluation of a synapomorphic DNA fragment for species-specific diagnosis. International Journal for Parasitology 32, 53–63.Google Scholar
Vodnala, M., Fijolek, A., Rofougaran, R., Mosimann, M. and Maser, P. (2008). Adenosine kinase mediates high affinity adenosine salvage in Trypanosoma brucei . Journal of Biological Chemistry 283, 5380–5388.CrossRefGoogle ScholarPubMed
Vodnala, S. K., Ferella, M., Lunde´N-Miguel, H., Betha, E. and Van Reet, N. (2009). Preclinical assessment of the treatment of second-stage African trypanosomiasis with cordycepin and deoxycoformycin. PLoS Neglected Tropical Diseases 3, e495.Google Scholar
Williamson, J. (1972). Further experiments with the nucleoside trypanocide, cordycepin. Transactions of the Royal Society of Tropical Medicine and Hygiene 66, 354–355.Google Scholar
Williamson, J. and Macadam, R. F. (1976). Drug effects on the fine structure of Trypanosoma rhodesiense: puromycin and its aminonucleoside, cordycepin and nucleocidin. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 130–137.Google Scholar
Williamson, J. and Scott-Finnigan, T. J. (1978). Trypanocidal activity of antitumor antibiotics and other metabolic inhibitors. Antimicrobial Agents and Chemotherapy 13, 735–744.Google Scholar