Changes in pentobarbital induced sleeping-time in mice infected with Schistosoma mansoni and immunosuppressed

Tonelli, Sônia Maria de Assis Fonseca; Brasileiro Filho, Geraldo; Goulart, Eugênio Marcos de Andrade; Coelho, Paulo Marcos Zech

doi:10.1590/S0036-46651995000200010

Abstracts

To evaluate whether the intensity of the hepatic granulomatous response induced by S. mansoni eggs plays a role in drug metabolism, mice were infected with 40 cercariae and tested to assess the sodic pentobarbital induced sleeping-time. To decrease the inflammatory reaction the animals were irradiated with 400 Rad or received azathioprine, 20mg/kg, 3 times a week, for 4 weeks, respectively in or beginning in the 33th post-infection day. In infected animals receiving azathioprine the area of the hepatic granulomas was smaller and the sleeping-time was similar to that of non-infected ones (controls). In mice infected and irradiated the granuloma dimensions were similar to those of animals only infected, in these two latter groups of animals, the sleeping-time was more prolonged than that of the control animals. These results show that: 1) mice with unaltered hepatic granulomatous reaction show reduction in metabolism of sodic pentobarbital; 2) granulomatous response diminished by azathioprine does not interfere with the capacity of metabolism of the anesthetic drug.

Schistosoma mansoni; lmmunosuppression; Sleeping-time; Drug metabolism; Granulomas

Para avaliar se a intensidade da reação granulomatosa hepática induzida por ovos de S. mansoni tem relação com o metabolismo de drogas, camundongos foram infectados com 40 cercárias e testados quanto ao tempo de anestesia pelo pentobarbital sódico. Para diminuir a resposta inflamatória usou-se irradiação com 400 Rad ou azatioprina na dose de 20mg/kg, 3 vezes por semana, por 4 semanas, respectivamente no ou a partir do 33º dia pós-infecção. Nos animais infectados que receberam azatioprina a área dos granulomas hepáticos foi menor e o tempo de anestesia mostrou-se igual ao dos animais não infectados (controles). Nos animais infectados e irradiados as dimensões dos granulomas foram semelhantes às dos animais apenas infectados; nestes dois grupos de animais o tempo de anestesia foi maior que o dos animais controles. Esses resultados mostram que: 1) animais com reação granulomatosa inalterada apresentam diminuição da metabolização do pentobarbital sódico; 2) resposta granulomatosa hepática diminuída pela azatioprina não interfere na capacidade de metabolização da droga anestésica.

SCHISTOSOMIASIS

Changes in pentobarbital induced sleeping-time in mice infected with Schistosoma mansoni and immunosuppressed

Alterações no tempo de anestesia pelo pentobarbital sódico em camundongos infectados pelo Schistosoma mansoni e imunossuprimidos

Sônia Maria de Assis Fonseca Tonelli^I; Geraldo Brasileiro Filho^II; Eugênio Marcos de Andrade Goulart^III; Paulo Marcos Zech Coelho^I

^IDepartamento de Parasitologia, Instituto de Ciências Biológicas

^IIDepartamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina

^IIIDepartamento de Pediatria, Faculdade de Medicina, UFMG

^{Correspondence to} Correspondence to: Prof. Paulo Marcos Zech Coelho GIDE/ICB/UFMG Caixa Postal 486 30161-970 Belo Horizonte, MG, Brasil

SUMMARY

To evaluate whether the intensity of the hepatic granulomatous response induced by S. mansoni eggs plays a role in drug metabolism, mice were infected with 40 cercariae and tested to assess the sodic pentobarbital induced sleeping-time. To decrease the inflammatory reaction the animals were irradiated with 400 Rad or received azathioprine, 20mg/kg, 3 times a week, for 4 weeks, respectively in or beginning in the 33th post-infection day. In infected animals receiving azathioprine the area of the hepatic granulomas was smaller and the sleeping-time was similar to that of non-infected ones (controls). In mice infected and irradiated the granuloma dimensions were similar to those of animals only infected, in these two latter groups of animals, the sleeping-time was more prolonged than that of the control animals. These results show that: 1) mice with unaltered hepatic granulomatous reaction show reduction in metabolism of sodic pentobarbital; 2) granulomatous response diminished by azathioprine does not interfere with the capacity of metabolism of the anesthetic drug.

Keywords:Schistosoma mansoni; lmmunosuppression; Sleeping-time; Drug metabolism; Granulomas

RESUMO

Para avaliar se a intensidade da reação granulomatosa hepática induzida por ovos de S. mansoni tem relação com o metabolismo de drogas, camundongos foram infectados com 40 cercárias e testados quanto ao tempo de anestesia pelo pentobarbital sódico. Para diminuir a resposta inflamatória usou-se irradiação com 400 Rad ou azatioprina na dose de 20mg/kg, 3 vezes por semana, por 4 semanas, respectivamente no ou a partir do 33º dia pós-infecção. Nos animais infectados que receberam azatioprina a área dos granulomas hepáticos foi menor e o tempo de anestesia mostrou-se igual ao dos animais não infectados (controles). Nos animais infectados e irradiados as dimensões dos granulomas foram semelhantes às dos animais apenas infectados; nestes dois grupos de animais o tempo de anestesia foi maior que o dos animais controles. Esses resultados mostram que: 1) animais com reação granulomatosa inalterada apresentam diminuição da metabolização do pentobarbital sódico; 2) resposta granulomatosa hepática diminuída pela azatioprina não interfere na capacidade de metabolização da droga anestésica.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 04/07/1994.

Aceito para publicação em 25/08/1994.

Financial support from CNPq, FAPEMIG, FINEP, PRPq (UFMG), Brasil, and WHO, Switzerland.

1. BUCHANAN, R.D.; FINE, D.P. & COLLEY, D.G. - Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. Amer. J. Path., 71: 207-218, 1973.
2. BYRAN, J.E. & VON LICHTEMBERG, F. - Altered schistosome granuloma formation in nude mice. Amer. J. trop. Med. Hyg., 26: 944-956, 1977.
3. CHA, Y.N. - Inducibility of the hepatic drug metabolizing capacity of S. mansoni infected mice. Amer. J. trop. Med. Hyg., 27: 1181-1187, 1978.
4. CHA, Y.N. & BUEDING, E. - Recovery of the hepatic drug-metabolizing capacity in mice infected with Schistosoma mansoni following curative chemotherapy with the schistosomicide 4-isothiocyano-4-nitrodiphenylamide (CGP540). Amer. J. trop. Med. Hyg., 27: 1188-1191, 1978.
5. CHA Y.N.; HEINE, H.S. & BUEDING, E. - Effect of unisexual Schistosoma mansoni infections on hepatic drug metabolism of mice. Amer. J. trop. Med. Hyg., 29: 227-233, 1980a.
6. CHA, Y.N.; BYRAN, J.E.; HEINE, H.S. & BUEDING, E. - Effect of Schistosoma mansoni infection on hepatic drug metabolizing capacity of athymic nude mice. Amer. J. trop. Med. Hyg., 29: 234-238, 1980b.
7. COELHO, P.M.Z.; FREIRE, A.C.T.; ARAUJO, F.G.; PELLEGRINO, J. & PEREIRA, L.H. - Effect of Schistosoma mansoni infection on pentobarbital induced sleeping-time in mice. Amer. J. trop. Med. Hyg., 26: 186-187, 1977.
8. DOMINGO, E.O.; COWAN, R.B.T. & WARREN, K.S. - The inhibition of granuloma formation around Schistosoma mansoni eggs. I. Immunosuppressive drugs. Amer. J. trop. Med. Hyg., 16: 284-292, 1967.
9. DOMINGO, E.O. & WARREN, K.S. - The inhibition of granuloma formation around Schistosoma mansoni eggs. II. Thymectomy. Amer. J. trop. Med. Hyg., 51: 757-766, 1967.
10. EPSTEIN, W.J.; FUKUYAMA, K.; DANNO, K. & KWAN-WONG, E. - Granulomatous inflammation in normal and athymic mice infected with Schistosoma mansoni. An ultrastructural study. J. Path., 127: 207-215, 1979.
11. HARVEY, S.C. - Hipnóticos e sedativos. In: GOODMAN, L.S. & GILMAN, A. As bases farmacológicas da terapęutica. 7. ed. Rio de Janeiro, Ed. Guanabara, 1987. p. 222-243.
12. HSU, C.K. - Immunopathology of schistosomiasis in athymic mice. Nature (Lond.), 262: 397-398, 1976.
13. LUCAS, S.; MUSALLAM, R.; BAIN, J. et al. - The pathological effects of immunosuppression of Schistosoma mansoni infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with hidrocortisone acetate. Trans. roy. Soc. trop. Med. Hyg., 24: 633-643, 1980.
14. McLAREN, D.J. & SMITHERS, S.R. - The immune response to schistosomes in experimental hosts. In: ROLLINSON, D. & SIMPSON, A.J.G. The biology of Schistosomes. From genes to latrines. London, Academic Press, 1987. p. 233-263.
15. PELLEGRINO, J. & SIQUEIRA, A.F. - Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Rev. bras. Malar., 8: 589-597, 1956.
16. PERROTO, J.L. & WARREN, K.S. - Inhibition of granuloma formation around Schistosoma mansoni eggs. IV-X. Irradiation. Amer. J. Path., 56: 279-291, 1969.
17. RASO, P.; ROCHA, O.A.; PEREIRA, L.H. & TAFURI, W.L. - Efeito da timectomia neonatal na esquistossomose mansoni experimental. Rev. Soc. bras. Med. trop., 16: 112-121, 1983.
18. VON LICHTEMBERG, F. - Host response to eggs of S. mansoni. I. Granuloma formation in the unsensitized laboratory mouse. Amer. J. Path., 41: 711-731, 1962.

Correspondence to:

Prof. Paulo Marcos Zech Coelho

GIDE/ICB/UFMG

Caixa Postal 486

30161-970 Belo Horizonte, MG, Brasil

Publication Dates

Publication in this collection
22 Feb 2007
Date of issue
Apr 1995

History

Received
04 July 1994
Accepted
25 Aug 1994

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

[1] 1. BUCHANAN, R.D.; FINE, D.P. & COLLEY, D.G. - Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. Amer. J. Path., 71: 207-218, 1973.

[2] 2. BYRAN, J.E. & VON LICHTEMBERG, F. - Altered schistosome granuloma formation in nude mice. Amer. J. trop. Med. Hyg., 26: 944-956, 1977.

[3] 3. CHA, Y.N. - Inducibility of the hepatic drug metabolizing capacity of S. mansoni infected mice. Amer. J. trop. Med. Hyg., 27: 1181-1187, 1978.

[4] 4. CHA, Y.N. & BUEDING, E. - Recovery of the hepatic drug-metabolizing capacity in mice infected with Schistosoma mansoni following curative chemotherapy with the schistosomicide 4-isothiocyano-4-nitrodiphenylamide (CGP540). Amer. J. trop. Med. Hyg., 27: 1188-1191, 1978.

[5] 5. CHA Y.N.; HEINE, H.S. & BUEDING, E. - Effect of unisexual Schistosoma mansoni infections on hepatic drug metabolism of mice. Amer. J. trop. Med. Hyg., 29: 227-233, 1980a.

[6] 6. CHA, Y.N.; BYRAN, J.E.; HEINE, H.S. & BUEDING, E. - Effect of Schistosoma mansoni infection on hepatic drug metabolizing capacity of athymic nude mice. Amer. J. trop. Med. Hyg., 29: 234-238, 1980b.

[7] 7. COELHO, P.M.Z.; FREIRE, A.C.T.; ARAUJO, F.G.; PELLEGRINO, J. & PEREIRA, L.H. - Effect of Schistosoma mansoni infection on pentobarbital induced sleeping-time in mice. Amer. J. trop. Med. Hyg., 26: 186-187, 1977.

[8] 8. DOMINGO, E.O.; COWAN, R.B.T. & WARREN, K.S. - The inhibition of granuloma formation around Schistosoma mansoni eggs. I. Immunosuppressive drugs. Amer. J. trop. Med. Hyg., 16: 284-292, 1967.

[9] 9. DOMINGO, E.O. & WARREN, K.S. - The inhibition of granuloma formation around Schistosoma mansoni eggs. II. Thymectomy. Amer. J. trop. Med. Hyg., 51: 757-766, 1967.

[10] 10. EPSTEIN, W.J.; FUKUYAMA, K.; DANNO, K. & KWAN-WONG, E. - Granulomatous inflammation in normal and athymic mice infected with Schistosoma mansoni. An ultrastructural study. J. Path., 127: 207-215, 1979.

[11] 11. HARVEY, S.C. - Hipnóticos e sedativos. In: GOODMAN, L.S. & GILMAN, A. As bases farmacológicas da terapęutica. 7. ed. Rio de Janeiro, Ed. Guanabara, 1987. p. 222-243.

[12] 12. HSU, C.K. - Immunopathology of schistosomiasis in athymic mice. Nature (Lond.), 262: 397-398, 1976.

[13] 13. LUCAS, S.; MUSALLAM, R.; BAIN, J. et al. - The pathological effects of immunosuppression of Schistosoma mansoni infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with hidrocortisone acetate. Trans. roy. Soc. trop. Med. Hyg., 24: 633-643, 1980.

[14] 14. McLAREN, D.J. & SMITHERS, S.R. - The immune response to schistosomes in experimental hosts. In: ROLLINSON, D. & SIMPSON, A.J.G. The biology of Schistosomes. From genes to latrines. London, Academic Press, 1987. p. 233-263.

[15] 15. PELLEGRINO, J. & SIQUEIRA, A.F. - Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Rev. bras. Malar., 8: 589-597, 1956.

[16] 16. PERROTO, J.L. & WARREN, K.S. - Inhibition of granuloma formation around Schistosoma mansoni eggs. IV-X. Irradiation. Amer. J. Path., 56: 279-291, 1969.

[17] 17. RASO, P.; ROCHA, O.A.; PEREIRA, L.H. & TAFURI, W.L. - Efeito da timectomia neonatal na esquistossomose mansoni experimental. Rev. Soc. bras. Med. trop., 16: 112-121, 1983.

[18] 18. VON LICHTEMBERG, F. - Host response to eggs of S. mansoni. I. Granuloma formation in the unsensitized laboratory mouse. Amer. J. Path., 41: 711-731, 1962.

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