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Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis

Published online by Cambridge University Press:  18 February 2016

T. MATA-SANTOS*
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
H. A. MATA-SANTOS
Affiliation:
Universidade Federal do Rio de Janeiro – Faculdade de Farmácia – Departamento de Análises Clínicas e Toxicológicas, Rio de Janeiro, Brazil
P. F. CARNEIRO
Affiliation:
Universidade Federal do Rio de Janeiro – Faculdade de Farmácia – Instituto de Pesquisa de Produtos Naturais, Rio de Janeiro, Brazil
K. C. G. DE MOURA
Affiliation:
Universidade Federal do Rio de Janeiro – Faculdade de Farmácia – Instituto de Pesquisa de Produtos Naturais, Rio de Janeiro, Brazil
J. M. FENALTI
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
G. B. KLAFKE
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
L. A. X. CRUZ
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
L. H. R. MARTINS
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
N. F. PINTO
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
M. C. F. R. PINTO
Affiliation:
Universidade Federal do Rio de Janeiro – Faculdade de Farmácia – Instituto de Pesquisa de Produtos Naturais, Rio de Janeiro, Brazil
M. E. A. BERNE
Affiliation:
Departamento de Microbiologia e Parasitologia, Universidade Federal de Pelotas – Instituto de Biologia, Pelotas, Brazil
P. E. A. DA SILVA
Affiliation:
Universidade Federal do Rio Grande –Núcleo de Pesquisa e Microbiologia Médica – Faculdade de Medicina, Rio Grande, Brazil
C. J. SCAINI
Affiliation:
Universidade Federal do Rio Grande – Faculdade de Medicina – Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rio Grande, Brazil
*
*Corresponding author: Universidade Federal do Rio Grande, Faculdade de Medicina, Área Interdisciplinar em Ciências Biomédicas – Laboratório de Parasitologia, Rua General Osório s/n, Área Acadêmica do Hospital Universitário, Rio Grande, RS 96200-190, Brazil. E-mail: farmatais@hotmail.com

Summary

Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2016 

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References

REFERENCES

Abo-Shehada, M. N. and Herbert, I. V. (1984). The migration of larval Toxocara canis in mice. II. Post-intestinal migration in primary infections. Veterinary Parasitology 17, 7583.CrossRefGoogle ScholarPubMed
Alderete, J. M. S., Jacob, C. M. A., Pastorino, A. C., Elefant, G. R., Castro, A. P. M., Fomin, A. B. F. and Chieffi, P. P. (2003). Prevalence of toxocara infection in schoolchildren from the Butantã Region, São Paulo, Brazil. Memorial Instituto Oswaldo Cruz 98, 593597.Google Scholar
Araújo, E. L., Alencar, J. R. B. and Neto, P. J. R. (2002). Lapachol: segurança e eficácia na terapêutica. Revista Brasileira de Farmacognosia 12, 5759.CrossRefGoogle Scholar
Avila, L. F. C., Conceição, F. R., Telmo, P. L., Dutra, G. F., Los Santos, D. G., Martins, L. H. R., Berne, M. E. A., Da Silva, P. E. A. and Scaini, C. J. (2012). Saccharomyces boulardii reduces infection intensity of mice with toxocariasis. Veterinary Parasitology 187, 337340.CrossRefGoogle ScholarPubMed
Błaszkowska, J., Góralzka, K., Wójcik, A., Kurnatowski, P. and Szwabe, K. (2015). Presence of Toxocara spp. eggs in children's recreation areas with varying degrees of access for animals. Annals of Agricultural and Environmental Medicine 22, 2327.CrossRefGoogle ScholarPubMed
Carneiro, P. F., Nascimento, S. B., Pinto, A. V., Pinto, M. C. F. R., Lechuga, G. C., Santos, D. O., Júnior, H. M. S., Resende, J. A. L. C., Bourguignon, S. C., Ferreira, V. F. (2012). New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms. Bioorganic & Medicinal Chemistry 20, 49955000.Google Scholar
Coelho, T. S., Silva, R. S. F., Pinto, A. V., Pinto, M. C. F. R., Sscaini, C. J., Moura, K. C. G. and Da Silva, P. A. (2010). Activity of β-lapachone derivatives against rifampicin-susceptible and–resistant strains of Mycobacterium tuberculosis . Tuberculosis 90, 293297.CrossRefGoogle ScholarPubMed
Curvelo, J. A. R., Barreto, A. L. S., dos Anjos, C. A., Santana, R. S., Alonso, A. N., Romanos, M. T. V., de Moura, K. C. G., Carneiro, P. F., Portela, M. B., Pinto, M. C. F. R. and Soares, R. M. A. (2015). 3-Indol carboxaldehyde, an imidazole synthesized from naphthoquinone β-lapachone downregulates Candida albicans biofilm. Medicinal Chemistry Research 24, 11551161.Google Scholar
Da Silva, M. N., Ferreira, V. F. and De Souza, M. C. B. V. (2003). Um panorama atual da química e da farmacologia de naftoquinonas, com ênfase na β-Lapachona e derivados. Quimica Nova 26, 407416.Google Scholar
De Almeida, E. R., Silva-Filho, A. A., Dos Santos, E. R. and Lopes, C. A. (1990). Antiinflammatory action of lapachol. Journal of Ethnopharmacology 29, 239241.CrossRefGoogle ScholarPubMed
De Andrade-Neto, V. F., Goulart, M. O. F., Da Silva, J. D., Da Silva, M. J., Pinto, M. C. F. R., Pinto, A. V., Zaliz, M. G., Carvalho, L. H. and Krettli, A. U. (2004). Antimalarial activity of phenazines from lapachol, beta-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo . Bioorganic & Medicinal Chemistry Letters 14, 11451949.Google Scholar
Delgado, O., Botto, C., Mattei, R. and Escalante, A. (1989). Effect of albendazole in experimental toxocariasis of mice. Annals of Tropical Medicine and Parasitology 83, 621624.CrossRefGoogle ScholarPubMed
De Moura, K. C. G., Emery, F. S., Pinto, C. N., Pinto, M. C. F. R., Dantas, A. P., Salomão, K., Castro, S. L. and Pinto, A. V. (2001). Trypanocidal activity of isolated naphthoquinones from Tabebuia and some heterocyclic derivatives: a review from an interdisciplinary study. Journal of the Brazilian Chemical Society 12, 325338.Google Scholar
De Moura, K. C. G., Salomão, K., Menna-Barreto, R. F. S., Emery, F. S., Pinto, M. C. F. R., Pinto, A. V. and Castro, S. L. (2004). Studies on the trypanocidal activity of semi-synthetic pyran[b-4,3]naphtho[1,2-d]imidazoles from b-lapachone. European Journal of Medicinal Chemistry 39, 639645.Google Scholar
De Savigny, D. H. (1975). In vitro maintenance of Toxocara canis larvae and a simple method for the production of Toxocara TES antigens for use in serodiagnostic tests for visceral larva migrans. Journal of Parasitology 61, 781782.Google Scholar
Despommier, D. (2003). Toxocariasis: clinical aspects, epidemiology, medical ecology, and molecular aspects. Clínical Microbiology Reviews 16, 265272.CrossRefGoogle ScholarPubMed
Eistert, B., Fink, H. and Müller, A. (1962). Umsetzungen substituierter p-Benzo- und –Naphthochinone mit Diazomethan. Chemische Berichte 95, 2403.Google Scholar
Elefant, R. G., Shimizu, S. H., Sanchez, M. C., Jacob, C. M. and Ferreira, A. W. (2006). A serological follow-up of toxocariasis patients after chemotherapy based on the detection of IgG, IgA and IgE antibodies by enzyme-linked immunosorbent assay. Journal of Clinical Laboratory Analysis 20, 169–72.Google Scholar
Falkenberg, M. B. (2004). Quinonas. In Farmacognosia: Da planta ao Medicamento (ed. Simões, C. M. O., Schenkel, E. P., Gosmann, G., Mello, J. C. P., Mentz, L. A. and Petrovick, P. R.), pp. 657683. Editora da UFRGS, Porto Alegre, RS.Google Scholar
Ferreira, V. F., Jorqueira, A., Souza, A. M. T., Silva, M. N., Souza, M. C. B. V., Gouvêa, R. M., Rodrigues, C. R., Pinto, A. V., Castro, H. C., Santos, D. O., Araújo, H. P. and Bourguignon, S. C. (2006). Trypanocidal agents with low cytotoxicity to mammalian cell line: a comparison of the theoretical and biological features of lapachone derivatives. Bioorganic & Medicinal Chemistry 14, 54595466.Google Scholar
Fillaux, J. and Magnaval, J. F. (2013). Laboratory diagnosis of human toxocariasis. Veterinary Parasitology 193, 327336.Google Scholar
Glickman, L. T. and Schantz, P. M. (1981). Epidemiology and pathogenesis of zoonotic toxocariasis. Epidemiologic Reviews 3, 230250.CrossRefGoogle ScholarPubMed
Glickman, L. T. and Magnaval, J. F. (1993). Zoonotic roundworm infections. Infectious Disease Clinics of North America 7, 717732.CrossRefGoogle ScholarPubMed
Hoffmeister, B., Glaeser, S., Flick, H., Pornschlegel, S., Suttorp, N. and Bergmann, F. (2007). Cerebral toxocariasis after consumption of raw duck liver. American Journal of Tropical Medicine and Hygiene 76, 600602.Google Scholar
Hogarth-Scott, R. S., Johansson, S. G. O. and Bennich, H. (1969). Antibodies to Toxocara in the sera of visceral larva migrans patients: the significance of raised levels of IgE. Clinical & Experimental Immunology 5, 619625.Google Scholar
Hooker, S. C. (1892). LVII—The constitution of “lapachic acid” (lapachol) and its derivatives. Journal of the Chemical Society 61, 611650.Google Scholar
Hotez, P. J. and Wilkins, P. P. (2009). Toxocariasis: America's most common neglected infection of poverty and a helminthiasis of global importance? PLoS Neglected Tropical Diseases 3, 14.Google Scholar
Hussain, H.; Krohn, K.; Ahmad, V. U., Miana, G. A. and Green, I. R. (2007). Lapachol: an overview. Arkivoc 2, 145171.Google Scholar
Jorqueira, A., Gouvêa, R. M., Ferreira, V. F., Da Silva, M. N., De Souza, M. C. B. V., Zuma, A. A., Cavalcanti, D. F. B., Araújo, H. P., Santos, D. O. and Bourguignon, S. C. (2006). Oxyrane derivative of α-lapachone is potent growth inhibitor of Trypanosoma cruzi epimastigote forms. Parasitology Research 99, 429433.CrossRefGoogle ScholarPubMed
Kennedy, M. W., Maizels, R. M., Meghji, M., Young, L., Quereshi, F. and Smith, H. V. (1987). Species-specific and common epitopes on the secreted and surface antigens of Toxocara cati and Toxocara canis infective larvae. Parasite Immunology 9, 407420.Google Scholar
Kubo, M., Itoh, Y., Tsuji, M., Oda, N., Takeuchi, H. and Itho, T. (1998). Polymerization of 1-Oxaspiro[2·5]octa-4,7-dien-6-ones. Macromolecules 31, 34693472.Google Scholar
Kumagai, Y., Shinkai, Y., Miura, T. and Cho, A. K. (2012). The chemical biology of naphthoquinones and its environmental implications. Annual Review of Pharmacology and Toxicology 52, 221247.CrossRefGoogle ScholarPubMed
Lescano, S. Z., Chieffi, P. P., Neto, V. A., Ikai, D. K. and Ribeiro, M. C. S. A. (2005). Anthelmintics in experimental toxocariasis: effects on larval recovery of Toxocara canis and on immune response. Jornal Brasileiro de Patologia e Medicina Laboratorial 41, 2124.Google Scholar
Magnaval, J. F. (1995). Comparative efficacy of diethylcarbamazine and mebendazole for the treatment of human toxocariasis. Parasitology 110, 529533.Google Scholar
Magnaval, J. F. and Glickman, L. T. (2006). Management and Treatment Options for Human Toxocariasis. Toxocara: The Enigmatic Parasite. Cabi Publishing, UK.Google Scholar
Magnaval, J. F., Glickman, L. T. and Dorchies, P. (1994). La Toxocarose, une zoonose helminthique majeure. Revue de Médicine Véterinaire 145, 611627.Google Scholar
Marmor, M., Glickman, L., Shofer, F., Faich, L. A., Rosenberg, C., Cornblatt, B. and Friedman, S. (1987). Toxocara canis infection in children: epidemiologic and neuropsycologic findings. American Journal of Public Health 77, 554559.Google Scholar
Mata-Santos, H. A., Dutra, F. F., Rocha, C. C., Lino, F. G., Xavier, F. R., Chinalia, L. A., Hossy, B. H., Castelo-Branco, M. T. L., Teodoro, A. J., Paiva, C. N. and Pyrrho, A. S. (2014). Silymarin reduces profibrogenic cytokines and reverses hepatic fibrosis in chronic murine schistosomiasis. Antimicrobial Agents and Chemotherapy 58, 20762083.CrossRefGoogle ScholarPubMed
Mata-Santos, T., Pinto, N. F., Mata-Santos, H. A., De Moura, K. G., Carneiro, P. F., Carvalho, T. S., Del Rio, K. P., Pinto, M. C. F. R., Martins, L. R., Fenalti, J. M., Da Silva, P. E. A. and Scaini, C. J. (2015). Anthelmintic activity of Lapachol, β-lapachone and its derivatives against Toxocara canis larvae. Revista do Instituto de Medicina Tropical de São Paulo 57, 197204.Google Scholar
Neves-Pinto, C., Dantas, A. P., De Moura, K. C. G., Emery, F. S., Polequevitch, P. F., Pinto, M. C. F. R., De Castro, S. L. and Pinto, A. V. (2000). Chemical reactivity studies with naphthoquinones from Tabebuia with anti-trypanosomal efficacy. Arzneimittelforschung Drug Research 50, 11201128.Google Scholar
Othman, A. A. (2012). Therapeutic battle against larval toxocariasis: are we still far behind? Acta Tropica 124, 171178.Google Scholar
Paller, V. G. V. and Chavez, E. R. C. (2014). Toxocara (Nematoda: Ascaridida) and other soil-transmitted helminth eggs contaminating soils in selected urban and rural areas in the Philippines. The Scientific World Journal 2014, 16.CrossRefGoogle Scholar
Pardee, A. B., Li, Y. Z. and Li, C. J. (2002). Cancer therapy with beta-lapachone. Current Cancer Drug Targets 2, 227242.Google Scholar
Pawlowski, Z. (2001). Toxocariasis in humans: clinical expression and treatment dilemma. Journal of Helminthology 75, 299305.CrossRefGoogle ScholarPubMed
Pinto, A. V., Lopes, J. N., Cruz, F. S., Vasconcellos, R., Sampaio, M. E., Pinto, M. C. F. R. and Gilbert, B. (1978). In vitro and in vivo evaluation of 1,4-naphthoquinones and 1,2-naphthoquinones derivatives against Trypanosoma cruzi . Annals of Tropical Medicine and Parasitology 72, 19.Google Scholar
Poulsen, C. S., Skov, S., Yoshida, A., Skallerup, P., Maruyama, H., Thamsborg, S. M. and Nejsum, P. (2015). Differential serodiagnostics of Toxocara canis and Toxocara cati – is it possible? Parasite Immunology 37, 204207.Google Scholar
Reis, M., Trinca, A., Ferreira, M. J. U., Monsalve-Puello, A. R. and Grácio, M. A. A. (2010). Toxocara canis: potential activity of natural products against second-stage larvae in vitro and in vivo . Experimental Parasitology 126, 191197.CrossRefGoogle ScholarPubMed
Roush, W. R., Gonzfilez, F. V., McKerrow, J. H. and Hansell, E. (1998). Design and synthesis of dipeptidyl α′,β′-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain. Bioorganic & Medicinal Chemistry Letters 8, 28092812.Google Scholar
Satou, T., Horiuchi, A., Akao, N., Koike, K., Futija, K. and Nikaido, T. (2005). Toxocara canis: search for a potential drug amongst β-carboline alkaloids – in vivo and mouse studies. Experimental Parasitology 110, 134139.CrossRefGoogle ScholarPubMed
Schoenardie, E., Scaini, C. J., Brod, C. S., Pepe, M. S., Villela, M. M., Mcbride, A. J. A., Borsuk, S. and Berne, M. E. A. (2013). Seroprevalence of Toxocara infection in children from Southern Brazil. Journal of Parasitology 99, 537539.Google Scholar
Smith, H., Holland, C., Taylor, M., Magnaval, J. F., Schantz, P. and Maizels, R. (2009). How common is human toxocariasis? Towards standardizing our knowledge. Trends in Parasitology 25, 182188.CrossRefGoogle Scholar
Sprenger, L. K., Green, K. T. and Molento, M. B. (2014). Geohelminth contamination of public areas and epidemiological risk factors in Curitiba, Brazil. Brazilian Journal of Veterinary Parasitology 23, 6973.Google ScholarPubMed
Thomson, R. H. (1971). Naturally Occurring Quinines, 2rd Edn. Academic, London.Google Scholar
Thomson, R. H. (1991). Distribution of naturally occurring quinines. Pharmaceutisch Weekblad 13, 7073.CrossRefGoogle Scholar
Wang, G. X. and Luo, Z. J. (1998). A novel method for the recovery of Toxocara canis in mice. Journal of Helminthology 72, 183184.Google Scholar