Antischistosomal activity of acridanone- hydrazones in Cebus monkeys experimentally infected with the SJ strain of Schistosoma mansoni

Coelho, Paulo Marcos Zech; Pereira, Leógenes Horácio; Mello, Rômulo Teixeira de

doi:10.1590/S0037-86821995000300003

Abstracts

In this study, four compounds were utilized at the dose of 12.5mg/kg body weight, p.o., to treat Cebus monkeys experimentally infected with about 200 cercariae of Schistosoma mansoni (SJ strain), via transcutaneous route. The oograms performed with rectal snips, as well as stool examinations carried out periodically, showed no viable eggs of the parasite, from day 29 to 226post-treatment. The perfusion undertaken after killing the animals showed absence of worms in the treated monkeys, whereas 83 worms were recovered from the control, thus corroborating the results obtained by means of oograms and coproscopy. These results confirm the efficacy of 9-acridanone- hydrazones previously tested against the LE strain of S. mansoni. The low curative dose and apparent absence of toxicity render these dmgs an important therapeutic reserve, taking into consideration the reports on the resistance of S. mansoni to the modern drugs oxamniquine and praziquantel.

Schistosoma mansoni; Cebus monkeys; Acridanone-hydrazone

No presente trabalho, quatro compostos foram utilizados na dose de 12,5mg/kg de peso, por via oral, em macacos infectados transcutaneamente com cerca de 200 cercárias de Schistosoma mansoni. Os oogramas realizados com fragmentos de mucosa retal e os exames de fezes realizados, periodicamente, demonstraram a ausência de ovos viáveis do parasito a partir do 29- até o 226a dia pós-tratamento. A perfusão, apôs sacrifício dos animais tratados, não detectou vermes, enquanto que do macaco cotztrole 83 vermes foram recuperados, confirmando assim os resultados dos oogramas e da coproscopia. Estes resultados confirmam a eficácia das 9-acridanonas- hydrazonas já observada anteriormente contra a cepa LE de S. mansoni. A baixa dosagem curativa e aparente ausência de toxicidade colocam estas drogas como uma reserva terapêutica importante, tendo em vista o relato de resistência do S. mansoni às drogas modernas oxamniquína e praziquantel.

Schistosoma mansoni; Macacos Cebus; Acridanona-hidrazonas

ARTICLES

Antischistosomal activity of acridanone- hydrazones in Cebus monkeys experimentally infected with the SJ strain of Schistosoma mansoni

Paulo Marcos Zech Coelho; Leógenes Horácio Pereira^* * Deceased 6 February, 1994 Departamentos de Parasitologia, Instituto de Ciências Biológicas, e de Análises Clínicas eToxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG. This study was supported in part by CNPq, FAPEMIG, PRPq/UFMG, Brazil, and by WHO, Switzerland. ; Rômulo Teixeira de Mello

^{Adress to correspondence} Adress to correspondence: Prof. Paulo Marcos Zech Coelho, Depto de Parasitologia. ICB/UFMG/Caixa Postal 486, 30161-970 Belo Horizonte, MG.

ABSTRACT

In this study, four compounds were utilized at the dose of 12.5mg/kg body weight, p.o., to treat Cebus monkeys experimentally infected with about 200 cercariae of Schistosoma mansoni (SJ strain), via transcutaneous route. The oograms performed with rectal snips, as well as stool examinations carried out periodically, showed no viable eggs of the parasite, from day 29 to 226post-treatment. The perfusion undertaken after killing the animals showed absence of worms in the treated monkeys, whereas 83 worms were recovered from the control, thus corroborating the results obtained by means of oograms and coproscopy. These results confirm the efficacy of 9-acridanone- hydrazones previously tested against the LE strain of S. mansoni. The low curative dose and apparent absence of toxicity render these dmgs an important therapeutic reserve, taking into consideration the reports on the resistance of S. mansoni to the modern drugs oxamniquine and praziquantel.

Keywords:Schistosoma mansoni. Cebus monkeys. Acridanone-hydrazone.

RESUMO

No presente trabalho, quatro compostos foram utilizados na dose de 12,5mg/kg de peso, por via oral, em macacos infectados transcutaneamente com cerca de 200 cercárias de Schistosoma mansoni. Os oogramas realizados com fragmentos de mucosa retal e os exames de fezes realizados, periodicamente, demonstraram a ausência de ovos viáveis do parasito a partir do 29- até o 226a dia pós-tratamento. A perfusão, apôs sacrifício dos animais tratados, não detectou vermes, enquanto que do macaco cotztrole 83 vermes foram recuperados, confirmando assim os resultados dos oogramas e da coproscopia. Estes resultados confirmam a eficácia das 9-acridanonas- hydrazonas já observada anteriormente contra a cepa LE de S. mansoni. A baixa dosagem curativa e aparente ausência de toxicidade colocam estas drogas como uma reserva terapêutica importante, tendo em vista o relato de resistência do S. mansoni às drogas modernas oxamniquína e praziquantel.

Palavras-chave:Schistosoma mansoni. Macacos Cebus. Acridanona-hidrazonas.

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Recebido para publicação em 24/08/94.

1. Araújo N, Katz N, Dias EF; Souza E Susceptibility to chemotherapeutic agents of strains of Schistosoma mansoni isolated from treated and untreated patients.The American Journal of Tropical Medicine and Hygiene 29:890-894,1980.
2. Barbosa FS, Barreto AC. Differences in susceptibility of Brazilian strains of Australorbis glabratus to Schistosoma mansoni Experimental Parasitology 9:137-140, I960.
3. Cioli D, Pica-Mattoccia L, Moroni R. Schistosoma mansoni: hyeanthone/oxamniquine resistance is controlled by a single autosomal recessive gene. Experimental Parasitological 75:425-432,1992.
4. Coelho PMZ, Pereira LH. Schistosoma mansoni: Preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected. Revista do Instituto de Medicina Tropical de São Paulo 33:50-57,1991.
5. Coelho PMZ, Raso P, Mello RT, Toppa NH. Dimensões do granuloma hepático produzido por ovos de duas linhagens geográficas do Schistosoma mansoni, no camundongo. Memórias do Instituto Oswaldo Cruz 84:213-217, 1989.
6. Dias LCS, Gonçalves ER. Schistosoma mansoni diz não às drogas. Ciência Hoje 14:22-25,1992.
7. Dias LCS, Pedro RJ, Deberaldini ER. Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents. Transactions of the Royal Society of Tropical Medicine and Hygiene 76:652-659,1982.
8. Files VS, Cram EB. A study on the comparative susceptibility of snails vector to strains of Schistosoma mansoni Journal of Parasitology 35:555-560,1949.
9. Katz N, Pellegrino J, Pompéu-Memória JM. Quantitative oogram method in Cebus monkeys experimentally infected with Schistosoma mansoni Journal of Parasitology 52:917-919, 1966.
10. Newton WL. The inheritance of susceptibility to infection with Schistosoma mansoni in Australorbis glabratus Experimental Parasitology 2; 242-257,1953.
11. Paraense WL, Correa R. Variation in susceptibility of populations of Australorbis glabratus to a strain of Schistosoma mansoni Revista do Instituto de Medicina Tropical de São Paulo 5:15- 22,1963.
12. Pellegrino J, Siqueira AP. Técnica de perfusão para colheita de Schistosoma mansoni em cobaias experimentalmente infestadas. Revista Brasileira de Malariologia 8: 589-597,1956.
13. Saoud MFA.The infectivity and pathogenicity of geographic strains of Schistosoma mansoni Transactions of the Royal Society of Tropical Medicine and Hygiene 60:585-600,1966.
14. Sturrock RF, Bain J,Webbe G, Doenhoff MJ, Stohler H. Parasitological evaluation of curative and subcurative doses of 9-Acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations in serum levels of anti-egg antibodies detected by ELISA. Transactions of the Royal Society of Tropical Medicine and Hygiene 81:188-192,1987.
15. Warren KS. Comparison of Puerto Rican, Brazilian, Egyptian and Tanzanian strains of Schistosoma mansoni in mice: penetration of cercariae, maturation on schistosomes and production of liver disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 61:795-802,1967.
16. World Health Organization. The role of chemotherapy in schistosomiasis control. WHO/Schisto/83.70, Revue. 1. World Health Organization 1:24,1983.

Adress to correspondence:

Prof. Paulo Marcos Zech Coelho,

Depto de Parasitologia.

ICB/UFMG/Caixa Postal 486,

30161-970

Belo Horizonte, MG.

*

Deceased 6 February, 1994

Departamentos de Parasitologia, Instituto de Ciências Biológicas, e de Análises Clínicas eToxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG. This study was supported in part by CNPq, FAPEMIG, PRPq/UFMG, Brazil, and by WHO, Switzerland.

Publication Dates

Publication in this collection
09 Apr 2013
Date of issue
Sept 1995

History

Accepted
24 Aug 1994
Received
24 Aug 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Araújo N, Katz N, Dias EF; Souza E Susceptibility to chemotherapeutic agents of strains of Schistosoma mansoni isolated from treated and untreated patients.The American Journal of Tropical Medicine and Hygiene 29:890-894,1980.

[2] 2. Barbosa FS, Barreto AC. Differences in susceptibility of Brazilian strains of Australorbis glabratus to Schistosoma mansoni Experimental Parasitology 9:137-140, I960.

[3] 3. Cioli D, Pica-Mattoccia L, Moroni R. Schistosoma mansoni: hyeanthone/oxamniquine resistance is controlled by a single autosomal recessive gene. Experimental Parasitological 75:425-432,1992.

[4] 4. Coelho PMZ, Pereira LH. Schistosoma mansoni: Preclinical studies with 9-acridanone-hydrazones in Cebus monkeys experimentally infected. Revista do Instituto de Medicina Tropical de São Paulo 33:50-57,1991.

[5] 5. Coelho PMZ, Raso P, Mello RT, Toppa NH. Dimensões do granuloma hepático produzido por ovos de duas linhagens geográficas do Schistosoma mansoni, no camundongo. Memórias do Instituto Oswaldo Cruz 84:213-217, 1989.

[6] 6. Dias LCS, Gonçalves ER. Schistosoma mansoni diz não às drogas. Ciência Hoje 14:22-25,1992.

[7] 7. Dias LCS, Pedro RJ, Deberaldini ER. Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents. Transactions of the Royal Society of Tropical Medicine and Hygiene 76:652-659,1982.

[8] 8. Files VS, Cram EB. A study on the comparative susceptibility of snails vector to strains of Schistosoma mansoni Journal of Parasitology 35:555-560,1949.

[9] 9. Katz N, Pellegrino J, Pompéu-Memória JM. Quantitative oogram method in Cebus monkeys experimentally infected with Schistosoma mansoni Journal of Parasitology 52:917-919, 1966.

[10] 10. Newton WL. The inheritance of susceptibility to infection with Schistosoma mansoni in Australorbis glabratus Experimental Parasitology 2; 242-257,1953.

[11] 11. Paraense WL, Correa R. Variation in susceptibility of populations of Australorbis glabratus to a strain of Schistosoma mansoni Revista do Instituto de Medicina Tropical de São Paulo 5:15- 22,1963.

[12] 12. Pellegrino J, Siqueira AP. Técnica de perfusão para colheita de Schistosoma mansoni em cobaias experimentalmente infestadas. Revista Brasileira de Malariologia 8: 589-597,1956.

[13] 13. Saoud MFA.The infectivity and pathogenicity of geographic strains of Schistosoma mansoni Transactions of the Royal Society of Tropical Medicine and Hygiene 60:585-600,1966.

[14] 14. Sturrock RF, Bain J,Webbe G, Doenhoff MJ, Stohler H. Parasitological evaluation of curative and subcurative doses of 9-Acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations in serum levels of anti-egg antibodies detected by ELISA. Transactions of the Royal Society of Tropical Medicine and Hygiene 81:188-192,1987.

[15] 15. Warren KS. Comparison of Puerto Rican, Brazilian, Egyptian and Tanzanian strains of Schistosoma mansoni in mice: penetration of cercariae, maturation on schistosomes and production of liver disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 61:795-802,1967.

[16] 16. World Health Organization. The role of chemotherapy in schistosomiasis control. WHO/Schisto/83.70, Revue. 1. World Health Organization 1:24,1983.