Ultrastructural alterations of intracellular stages and effects on blood forms of Trypanosoma cruzi induced in vivo by 2-amino-5-(1-methyil-5-nitro-2-imidazolyl)-1,3,4 - Thiadiazole

Maria, Thaisa de Almeida; Filardi, Leny de Sousa; Brener, Zigman

doi:10.1590/S0037-86821984000200008

Abstracts

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.

Trypanosoma cruzi; Nitroimidazo-thiadiazole; Electron microscopy

Um estudo com microscopia eletrônica mostrou que a administração de dose única (500 mg/kg, p.o.) do composto 2-amino-5-(1-metil-5-nitro-2-imidazolil)-1 3, 4-tiadiazole induz, em camundongos inoculados com T. cruzi, lesões degenerativas das formas intracelulares do parasita. Alterações ultra estruturais são observadas 6 horas após a administração da droga e destruição ocorre em 18-36 horas. Tripomastigotas também desaparecem do sangue circulante dos animais 4-6 horas após o tratamento. O efeito em ambos os estágios evolutivos do T. cruzi é aparentemente responsável pelos efeitos in vivo desse derivado que é o mais ativo composto já testado em nosso laboratório na doença de Chagas.

Trypanosoma cruzi; Nitroimidazol - Tiadiazole; Microscopia eletrônica

ARTICLES

Ultrastructural alterations of intracellular stages and effects on blood forms of Trypanosoma cruzi induced in vivo by 2-amino-5-(1-methyil-5-nitro-2-imidazolyl)-1,3,4 - Thiadiazole¹ 1 Supported by CNPq-FINEP.

Thaisa de Almeida Maria^I; Leny de Sousa Filardi^II; Zigman Brener^III

^IDepartamento de Morfologia, ICB/UFMG

^IIDepartamento de Zoologia, ICB/UFMG

^IIICentro de Pesquisas René Rachou, FIOCRUZ, Av. Augusto de Lima, 1715 - C.P. 1743, 30.000 - Belo Horizonte, Brasil (Address for Correspondence)

ABSTRACT

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.

Keywords:Trypanosoma cruzi. Nitroimidazo-thiadiazole. Electron microscopy.

RESUMO

Um estudo com microscopia eletrônica mostrou que a administração de dose única (500 mg/kg, p.o.) do composto 2-amino-5-(1-metil-5-nitro-2-imidazolil)-1 3, 4-tiadiazole induz, em camundongos inoculados com T. cruzi, lesões degenerativas das formas intracelulares do parasita. Alterações ultra estruturais são observadas 6 horas após a administração da droga e destruição ocorre em 18-36 horas. Tripomastigotas também desaparecem do sangue circulante dos animais 4-6 horas após o tratamento. O efeito em ambos os estágios evolutivos do T. cruzi é aparentemente responsável pelos efeitos in vivo desse derivado que é o mais ativo composto já testado em nosso laboratório na doença de Chagas.

Palavras-chave:Trypanosoma cruzi. Nitroimidazol - Tiadiazole. Microscopia eletrônica.

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1. Andrade SG, Figueira RM. Estudo experimental sobre a ação terapêutica da droga Ro 7-1051 na infecção por diferentes cepas do Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 19: 335- 341, 1977.
2. Brener Z. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 4: 389-396, 1962.
3. Brener Z, Chiari E. Variações morfológicas observadas em diferentes amostras do Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 5: 220- 224, 1963.
4. Brener Z, Tafuri WL, Maria TA. An electron microscope study of Trypanosoma cruzi intracellular forms in mice treated with an active nitrofuran compound. Revista do Instituto de Medicina Tropical de São Paulo 11: 245-249, 1969.
5. Docampo R, Moreno SNJ, Stopanni AOM, Leon W, Cruz FE, Villalta F, Muniz RFA. Mechanism of nifurtimox toxicity in different forms of Trypanosoma cruzi Biochemistry Pharmacology 30: 1947-1951, 1981.
6. Filardi LS. Brener Z. A nitroimidazole-thiadiazole derivative with curative action in experimental Trypanosoma cruzi infections. Annals of Tropical Medicine and Parasitology 76: 293-297, 1982.
7. Filardi LS, Brener Z. A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents. Memórias do Instituto Oswaldo Cruz (in press).
8. Haberkom A, Gõnnert R. Animal experimental investigations in the activity of nifurtimox against Trypanosoma cruzi Arzneimittel Forschung 22: 1570-1581, 1972.
9. Lages- Silva E, Filardi LS, Gilbert ME, Gilbert B, Brener Z. Participation of macrophages in the clearance of Trypanosoma cruzi from the blood of mice submitted to specific treatment. X Reunião Anual sobre Pesquisa Básica em Doenças de Chagas, Caxambú, novembro 1983.
10. Moreno SNJ, Docampo R, Mason RP, Leon W, Stopanni AOM. Different behaviour of benznidazole as free radical generator with mammalian and Trypanosoma cruzi microsomal preparations. Archives of Biochemistry and Biophysics 218: 585-591, 1983.
11. Schlemper Jr BR. Caracterização de cepas do Trypanosoma cruzi isoladas de pacientes com diferentes formas clinicas da doença de Chagas. Tese de Doutorado, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 1982.
12. Voigt WH, Bock M, Gönnert R. Ultrastructural observations on the activity of nifurtimox on the causative organism of Chagas' disease. I. Trypanosoma cruzi in tissue cultures. Arzneimittel Forschung 22: 1586-1589, 1972.

1

Supported by CNPq-FINEP.

Publication Dates

Publication in this collection
07 June 2013
Date of issue
June 1984

History

Received
15 Dec 1983
Accepted
15 Dec 1983

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

[1] 1. Andrade SG, Figueira RM. Estudo experimental sobre a ação terapêutica da droga Ro 7-1051 na infecção por diferentes cepas do Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 19: 335- 341, 1977.

[2] 2. Brener Z. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 4: 389-396, 1962.

[3] 3. Brener Z, Chiari E. Variações morfológicas observadas em diferentes amostras do Trypanosoma cruzi Revista do Instituto de Medicina Tropical de São Paulo 5: 220- 224, 1963.

[4] 4. Brener Z, Tafuri WL, Maria TA. An electron microscope study of Trypanosoma cruzi intracellular forms in mice treated with an active nitrofuran compound. Revista do Instituto de Medicina Tropical de São Paulo 11: 245-249, 1969.

[5] 5. Docampo R, Moreno SNJ, Stopanni AOM, Leon W, Cruz FE, Villalta F, Muniz RFA. Mechanism of nifurtimox toxicity in different forms of Trypanosoma cruzi Biochemistry Pharmacology 30: 1947-1951, 1981.

[6] 6. Filardi LS. Brener Z. A nitroimidazole-thiadiazole derivative with curative action in experimental Trypanosoma cruzi infections. Annals of Tropical Medicine and Parasitology 76: 293-297, 1982.

[7] 7. Filardi LS, Brener Z. A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents. Memórias do Instituto Oswaldo Cruz (in press).

[8] 8. Haberkom A, Gõnnert R. Animal experimental investigations in the activity of nifurtimox against Trypanosoma cruzi Arzneimittel Forschung 22: 1570-1581, 1972.

[9] 9. Lages- Silva E, Filardi LS, Gilbert ME, Gilbert B, Brener Z. Participation of macrophages in the clearance of Trypanosoma cruzi from the blood of mice submitted to specific treatment. X Reunião Anual sobre Pesquisa Básica em Doenças de Chagas, Caxambú, novembro 1983.

[10] 10. Moreno SNJ, Docampo R, Mason RP, Leon W, Stopanni AOM. Different behaviour of benznidazole as free radical generator with mammalian and Trypanosoma cruzi microsomal preparations. Archives of Biochemistry and Biophysics 218: 585-591, 1983.

[11] 11. Schlemper Jr BR. Caracterização de cepas do Trypanosoma cruzi isoladas de pacientes com diferentes formas clinicas da doença de Chagas. Tese de Doutorado, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 1982.

[12] 12. Voigt WH, Bock M, Gönnert R. Ultrastructural observations on the activity of nifurtimox on the causative organism of Chagas' disease. I. Trypanosoma cruzi in tissue cultures. Arzneimittel Forschung 22: 1586-1589, 1972.