Ação dos sucos digestivos sobre a absorção e destino do bcg Oral

Mortatti, Rodnei C.; Maia, Luiz Carlos S.; Fonseca, Leila

doi:10.1590/S0037-86821986000400010

Resumos

Estudou-se a ação do suco gástrico artificial e suco duodenal humano sobre a vacina BCG, bem como a absorção e destino desta após administração intragástrica em camundongos. O contato de 2 horas do bacilo com o suco gástrico provocou uma diminuição significante do consumo de oxigênio e uma moderada perda da viabilidade. O suco duodenal induziu marcante decréscimo da respiração bacilar egrande redução da viabilidade. O BCG foi marcado com carbono-14 usando-se 14C-glicerol como precursor dos lipidios micobacterianos. Níveis similares de radioatividade foram obtidos nos órgãos dos animais, 24 horas após administração intragástrica de 14C- BCG, 14C-BCG rompido por ultra-som e 14C-glicerol. Os níveis de 14C-BCG permaneceram estáveis do 6º ao 24º dia, enquanto o sonicado de 14C-BCG e 14C-glicerol definiram um processo de decaimento biológico. As curvas de biodecaimento no intestino delgado e no fígado indicaram que o processo de absorção foi desencadeado rapidamente e alcançou seu nível máximo às 24 horas, decaindo em seguida de acordo com a complexidade química do material dado aos camundongos. Não foram isolados bacilos viáveis dos órgãos dos animais que receberam BCG não marcado. Pode-se concluir, portanto, que a maioria dos bacilos foram absorvidos intactos mas não viáveis.

Micobactéria; BCG oral; Sucos digestivos; Carbono-14; Absorção; Biodisponibilidade

The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability, as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fali of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, 14C -glycerol. The levels ofradioactivity recovered at thefirstday in the organs ofmice receiving either gastric instillation of14C-BCG, sonically disrupted 14-BCG or 14C glycerol were very similar. Subsequently, sonicated 14C-BCG and 14C -glycerol were involved in a biological decay process, while the level of 14C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping there after according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive.

Mycobacteria; Oral BCG; Digestive juices; 14C-labelling; Absorption; Biovailability

ARTIGOS

Ação dos sucos digestivos sobre a absorção e destino do bcg Oral

Rodnei C. Mortatti^I; Luiz Carlos S. Maia^II; Leila Fonseca^I

^IDepartamentos de Imunologia e Microbiologia Médica. Instituto de Microbiologia, Universidade Federal do Rio de Janeiro

^IIFundação Ataulpho de Paiva, Rio de Janeiro

^{Endereço para correspondência} Endereço para correspondência: Dr. Rodnei C. Mortatti Dept o de Imunologia Instituto de Microbiologia UFRJ, CCS, Bloco I. 21941 Rio de Janeiro, RJ, Brasil.

RESUMO

Estudou-se a ação do suco gástrico artificial e suco duodenal humano sobre a vacina BCG, bem como a absorção e destino desta após administração intragástrica em camundongos. O contato de 2 horas do bacilo com o suco gástrico provocou uma diminuição significante do consumo de oxigênio e uma moderada perda da viabilidade. O suco duodenal induziu marcante decréscimo da respiração bacilar egrande redução da viabilidade. O BCG foi marcado com carbono-14 usando-se ¹⁴C-glicerol como precursor dos lipidios micobacterianos. Níveis similares de radioatividade foram obtidos nos órgãos dos animais, 24 horas após administração intragástrica de ¹⁴C- BCG, ¹⁴C-BCG rompido por ultra-som e ¹⁴C-glicerol. Os níveis de ¹⁴C-BCG permaneceram estáveis do 6^o ao 24^o dia, enquanto o sonicado de ¹⁴C-BCG e ¹⁴C-glicerol definiram um processo de decaimento biológico. As curvas de biodecaimento no intestino delgado e no fígado indicaram que o processo de absorção foi desencadeado rapidamente e alcançou seu nível máximo às 24 horas, decaindo em seguida de acordo com a complexidade química do material dado aos camundongos. Não foram isolados bacilos viáveis dos órgãos dos animais que receberam BCG não marcado. Pode-se concluir, portanto, que a maioria dos bacilos foram absorvidos intactos mas não viáveis.

Palavras-chave: Micobactéria. BCG oral. Sucos digestivos. Carbono-14. Absorção. Biodisponibilidade.

ABSTRACT

The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability, as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fali of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, ¹⁴C -glycerol. The levels ofradioactivity recovered at thefirstday in the organs ofmice receiving either gastric instillation of14C-BCG, sonically disrupted ¹⁴-BCG or ¹⁴C glycerol were very similar. Subsequently, sonicated ¹⁴C-BCG and ¹⁴C -glycerol were involved in a biological decay process, while the level of ¹⁴C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping there after according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive.

Keywords: Mycobacteria. Oral BCG. Digestive juices. ¹⁴C-labelling. Absorption. Biovailability.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Recebido para publicação em 10/3/86.

Financiado pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) e Fundação Ataulpho de Paiva.

1. Assis A. Concurrent BCG vaccination. Diseases of the Chest 16:266-269, 1949.
2. Assis A. The oral application of BCG. Advances in Tuberculosis Research 8:105-122, 1957.
3. Bailey NTJ. Statistical methods in biology. John Wiley & Sons Inc. 5th edition, New York, 1959.
4. Baldwin RW, Hopper DG, Pimm MV. Influence of orally administered BCG on growth of transplantable rat tumors. British Journal of Cancer 31:124-128, 1975.
5. Bast RC, Bast BS. Criticai review ofpreviously reported animal studies of tumor immunotherapy with nonspecific immunostimulants. Annals of the New York Academy of Sciences 277:60-92, 1976.
6. Calmette A, Well-Halle B, Saenz A, Costil R. Demonstration experimentale du passage de bacilles-vaccins BCG a travers la muqueuse de l'intestin chez l'enfant et chez le sing. Bulletin de l'Academie Nationale de Medecine 110:203-206, 1933.
7. Carter PB, Collins FM. The route of enteric infection in normal mice. Journal of Experimental Medicine 139:1189-1203, 1974.
8. Gemez-Rieux C, Tacquet A, F abre M, Gerard A, Voisin C. Absorption digestive du BCG chez les cobayes et les souris avant et aprés la vaccination. Annales de 1'Institut Pasteur de Lille 6:94-115, 1953-1954.
9. Gemez-Rieux C, Breton A, Tacquet A. Premiers essais d'absorption de BCG à dose massive et répétés chez les enfants allergiques. Archives Françaises de Pediatrie 11:291-295, 1954.
10. Gemez-Rieux C, Breton A, Tacquet A, Gerard A, Fabre M, Piat M. Vaccination antituberculeuse par voie digestive chez les sujets allergiques. I. Etude experimentale. II. Etude clinique. Revue de Tuberculose et de Pneumologie 18:677-700, 1954.
11. Janicki BW, Wright Jr. GL, Good RC, Chaparas SD. Comparison of antigens in sonic and pressure cell extracts of Mycobacterium tuberculosis Infection and Immunity 13:425-437, 1976.
12. Joel DD, Laissue JA, LeFreve ME. Distribution and fate of ingested carbon particles in mice. Journal of Reticuloendothelial Society 24:477-487, 1978.
13. LeFreve ME, Olivo R, Joel DD. Accumulation of latex particles in Peyer's patches and their subsequent appearence in villi and mesenteric lymph nodes. Proceedings of the Society of Experimental Biology and Medicine 159:298-302, 1978.
14. LeFreve ME, Hammer R, Joel DD. Macrophages of the mammalian small intestine: a review. Journal of Reticuloendothelial Society 26:553-573, 1979.
15. Lewis MG, Jerry LM, Rodwen TM, Phillips TM, Shibata H, C apek A. Some eftects of oral administration of BCG on immune response in cancer patients. In: Lamoureaux G, Turcotte R, Portelance V (eds). BCG in cancer immunotherapy. Grune & Stratton, New York, p. 339-358, 1976.
16. MacDonald AS, Norvell ST, Bordutha IA. Effects of oral BCG in solid tumors. In: Lamoureaux G, Turcotte R, Portelance V (eds). BCG in cancer immunotherapy. Grune & Stratton, New York, p. 133-138, 1976.
17. MacDonald TT, Carter PB. Cell-mediated immunity of intestinal infection. Infection and Immunity 28:516-523, 1980.
18. Magarão MI, Brascher HM, Vargens JR, Mortatti RC, Lima AO. Imunidade humoral e celular em crianças vacinadas com BCG pela via oral. Brazilian Journal of Medical and Biological Research 10:175-180, 1977.
19. Negre L, Bretey J, Roy D. Etude de l'allergie à la tuberculine chez le cobayes par ingestion de grosses doses de BCG. Annales de L'Institut Pasteur 98:1-6, 1960.
20. Olinto M. The Brazilian experience in prevention of tuberculosis with a concurrent method of BCG vaccination. Pediatrics 19:833-844, 1957.
21. Pasquier JF, Lucel Y. Preuve autoradiographic du passage intestinal chez la souris de bacilles BCG vivants et de bacilles tuberculeux bovins marques au ¹⁴C administrés par voie digestive. Comptes Rendus de Séances de la Société de Biologie 155:1930-1940, 1961.
22. Remington JS, Melton ML, Jacobs L. Chronic toxoplasma infection in the uterus. Journal of Laboratory and Clinical Medicine 58:879-883, 1960.
23. Rosemberg J. Present status of the oral BCG vaccination. O Hospital 42:15-20, 1952.
24. Sanders E, Ashworth CTA. A study of particulate intestinal absorption and hepatocellular uptake. Experimental Cell Research 22:137-145, 1961.
25. Shibata HR, Jerry LM, Lewis MG, Mansel PWA, Capek A, Marquis G. Immunotherapy of human malignant melanoma with irradiated tumor cells, oral BCG and levamisole. Annals of the New York Academy of Sciences 277:355-366, 1976.
26. Snedecor GW, Cochran WG. Statistical methods, 6th edition. The lowa State University Press, Iowa, p. 447- 471, 1976.
27. Tepper BS. Differences in the utilization of glycerol and glucose by Mycobacterium phlei Journal of Bacteriology 95: 1713-1717, 1968.
28. Tokunaga T, Taguchi S, Chino F, Murohashi T. Immunotherapeutic trials of murine and guinea-pig solid tumors by oral administration of BCG. Japanese Journal of Medical Science and Biology 32:1-18, 1979.
29. Toma JM, Penderleith IH, Clements DV, Landi S. Observations in immunotherapy of lymphoma and melanoma patients. Clinical and Experimental Immunology 21:82-96, 1975.
30. Varella AD, Bandeira DC, Amorim AR, Calvis LA, Santos IO, Escaleira N, Gentil F. Treatment of disseminated malignant melanoma with high-dose oral BCG. Cancer 48:1353-1362, 1981.

Endereço para correspondência:

Dr. Rodnei C. Mortatti

Dept

^o de Imunologia

Instituto de Microbiologia

UFRJ, CCS, Bloco I.

21941

Rio de Janeiro, RJ, Brasil.

Datas de Publicação

Publicação nesta coleção
06 Jun 2013
Data do Fascículo
Dez 1986

Histórico

Recebido
10 Mar 1986
Aceito
10 Mar 1986

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

[1] 1. Assis A. Concurrent BCG vaccination. Diseases of the Chest 16:266-269, 1949.

[2] 2. Assis A. The oral application of BCG. Advances in Tuberculosis Research 8:105-122, 1957.

[3] 3. Bailey NTJ. Statistical methods in biology. John Wiley & Sons Inc. 5th edition, New York, 1959.

[4] 4. Baldwin RW, Hopper DG, Pimm MV. Influence of orally administered BCG on growth of transplantable rat tumors. British Journal of Cancer 31:124-128, 1975.

[5] 5. Bast RC, Bast BS. Criticai review ofpreviously reported animal studies of tumor immunotherapy with nonspecific immunostimulants. Annals of the New York Academy of Sciences 277:60-92, 1976.

[6] 6. Calmette A, Well-Halle B, Saenz A, Costil R. Demonstration experimentale du passage de bacilles-vaccins BCG a travers la muqueuse de l'intestin chez l'enfant et chez le sing. Bulletin de l'Academie Nationale de Medecine 110:203-206, 1933.

[7] 7. Carter PB, Collins FM. The route of enteric infection in normal mice. Journal of Experimental Medicine 139:1189-1203, 1974.

[8] 8. Gemez-Rieux C, Tacquet A, F abre M, Gerard A, Voisin C. Absorption digestive du BCG chez les cobayes et les souris avant et aprés la vaccination. Annales de 1'Institut Pasteur de Lille 6:94-115, 1953-1954.

[9] 9. Gemez-Rieux C, Breton A, Tacquet A. Premiers essais d'absorption de BCG à dose massive et répétés chez les enfants allergiques. Archives Françaises de Pediatrie 11:291-295, 1954.

[10] 10. Gemez-Rieux C, Breton A, Tacquet A, Gerard A, Fabre M, Piat M. Vaccination antituberculeuse par voie digestive chez les sujets allergiques. I. Etude experimentale. II. Etude clinique. Revue de Tuberculose et de Pneumologie 18:677-700, 1954.

[11] 11. Janicki BW, Wright Jr. GL, Good RC, Chaparas SD. Comparison of antigens in sonic and pressure cell extracts of Mycobacterium tuberculosis Infection and Immunity 13:425-437, 1976.

[12] 12. Joel DD, Laissue JA, LeFreve ME. Distribution and fate of ingested carbon particles in mice. Journal of Reticuloendothelial Society 24:477-487, 1978.

[13] 13. LeFreve ME, Olivo R, Joel DD. Accumulation of latex particles in Peyer's patches and their subsequent appearence in villi and mesenteric lymph nodes. Proceedings of the Society of Experimental Biology and Medicine 159:298-302, 1978.

[14] 14. LeFreve ME, Hammer R, Joel DD. Macrophages of the mammalian small intestine: a review. Journal of Reticuloendothelial Society 26:553-573, 1979.

[15] 15. Lewis MG, Jerry LM, Rodwen TM, Phillips TM, Shibata H, C apek A. Some eftects of oral administration of BCG on immune response in cancer patients. In: Lamoureaux G, Turcotte R, Portelance V (eds). BCG in cancer immunotherapy. Grune & Stratton, New York, p. 339-358, 1976.

[16] 16. MacDonald AS, Norvell ST, Bordutha IA. Effects of oral BCG in solid tumors. In: Lamoureaux G, Turcotte R, Portelance V (eds). BCG in cancer immunotherapy. Grune & Stratton, New York, p. 133-138, 1976.

[17] 17. MacDonald TT, Carter PB. Cell-mediated immunity of intestinal infection. Infection and Immunity 28:516-523, 1980.

[18] 18. Magarão MI, Brascher HM, Vargens JR, Mortatti RC, Lima AO. Imunidade humoral e celular em crianças vacinadas com BCG pela via oral. Brazilian Journal of Medical and Biological Research 10:175-180, 1977.

[19] 19. Negre L, Bretey J, Roy D. Etude de l'allergie à la tuberculine chez le cobayes par ingestion de grosses doses de BCG. Annales de L'Institut Pasteur 98:1-6, 1960.

[20] 20. Olinto M. The Brazilian experience in prevention of tuberculosis with a concurrent method of BCG vaccination. Pediatrics 19:833-844, 1957.

[21] 21. Pasquier JF, Lucel Y. Preuve autoradiographic du passage intestinal chez la souris de bacilles BCG vivants et de bacilles tuberculeux bovins marques au ¹⁴C administrés par voie digestive. Comptes Rendus de Séances de la Société de Biologie 155:1930-1940, 1961.

[22] 22. Remington JS, Melton ML, Jacobs L. Chronic toxoplasma infection in the uterus. Journal of Laboratory and Clinical Medicine 58:879-883, 1960.

[23] 23. Rosemberg J. Present status of the oral BCG vaccination. O Hospital 42:15-20, 1952.

[24] 24. Sanders E, Ashworth CTA. A study of particulate intestinal absorption and hepatocellular uptake. Experimental Cell Research 22:137-145, 1961.

[25] 25. Shibata HR, Jerry LM, Lewis MG, Mansel PWA, Capek A, Marquis G. Immunotherapy of human malignant melanoma with irradiated tumor cells, oral BCG and levamisole. Annals of the New York Academy of Sciences 277:355-366, 1976.

[26] 26. Snedecor GW, Cochran WG. Statistical methods, 6th edition. The lowa State University Press, Iowa, p. 447- 471, 1976.

[27] 27. Tepper BS. Differences in the utilization of glycerol and glucose by Mycobacterium phlei Journal of Bacteriology 95: 1713-1717, 1968.

[28] 28. Tokunaga T, Taguchi S, Chino F, Murohashi T. Immunotherapeutic trials of murine and guinea-pig solid tumors by oral administration of BCG. Japanese Journal of Medical Science and Biology 32:1-18, 1979.

[29] 29. Toma JM, Penderleith IH, Clements DV, Landi S. Observations in immunotherapy of lymphoma and melanoma patients. Clinical and Experimental Immunology 21:82-96, 1975.

[30] 30. Varella AD, Bandeira DC, Amorim AR, Calvis LA, Santos IO, Escaleira N, Gentil F. Treatment of disseminated malignant melanoma with high-dose oral BCG. Cancer 48:1353-1362, 1981.