Effect of Glutamine on the Methotrexate Induced Gut Barrier Damage, Bacterial Translocation and Weight Changes in a Rat Model

백서에서 Methotrexate에 의하여 유발된 장관장벽손상 및 장내세균전위와 중량 변화에 대한 글루타민의 효과

  • Kim, Eun-Jeong (Department of Health Technology Planning and Evaluation Board, Korea Health Industry Developement Institute) ;
  • Kim, Jeong-Wook (Department of internal Medicine, Chungang University College of Medicine)
  • 김은정 (한국보건산업진흥원 연구사업지원본부) ;
  • 김정욱 (중앙대학교 의과대학 내과학교실)
  • Published : 2007.02.28

Abstract

The aim of this study was to examine whether administration of glutamine are able to prevent the methotrexate induced gut barrier damage, bacterial translocation, and weight changes. The animals with glutamine were fed with L-glutamine (1.2 and 2.4 mg/kg/day) for 7 days before methotrexate administration (20 mg/kg orally). 48 hour after methotrexate administration, intestinal permeability were measured for an assessment of the gut barrier dysfunction. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric lymph node (MLN), liver spleen, kidney and heart were measured for an assessment of the enteric bacterial number and bacterial translocation. Amounts of food intake, body weight changes and organ weight changes of liver spleen, kidney and heart were measured. Methotrexate administration caused body and liver weight loss regardless amounts of food intakes. Methotrexate induced increasing intestinal permeability, enteric bacterial undergrowth and bacterial translocation to MLN, liver and spleen, but not kidney and heart. The supplements with glutamine reduced the intestinal permeability bacterial translocation, and not influences enteric bacterial number, and body and liver weight changes. This study suggested that glutamine might effectively reduce methotrexate induced intestinal damage and bacterial translocation, but not influence body and organ weight loss.

Keywords

References

  1. 박원 : 류마티스관절염 환자에서 Methotrexate 부작용의 원인과 엽산 대사. 대한내과학회지 67, 109 (2004)
  2. Health and Public Policy Committee, American College of Physicians : Methotrexate in rheumatoid arthritis. Ann. Intern. Med. 107, 418 (1987)
  3. Mao, Y., Nobaek, S., Kasravi, B., Adawi, D., Stenram, U., Molin, G. and Jeppsson, B. : The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats. Gastroenterology 111, 334 (1996)
  4. Lobo, E. D. and Balthasar, J. P. : Pharmacokineticpharmacodynamic modeling of methotrexate-induced toxicity in mice. J. Pharm. Sci. 92, 1654 (2003) https://doi.org/10.1002/jps.10431
  5. Iqbal, M. P., Saeed, S. A., Pertani, S. and Mehboobali, N. : Additive effect of indomethacin and methotrexate on suppression of growth in rats. Biopharm. Drug Dispos. 20, 389 (1999)
  6. Ellis, M. : Preventing microbial translocation in haematological malignancy. Br. J. Haematol. 125, 282 (2004) https://doi.org/10.1111/j.1365-2141.2004.04903.x
  7. Miller, A. L. : Therapeutic considerations of L-glutamine: a review of the literature. Altern. Med. Rev. 4, 239 (1999)
  8. Marks, S. L., Cook, A. K., Reader, R., Kass, P. H., Theon, A. P., Greve, C. and Rogers, Q. R. : Effects of glutamine supplementation of an amino acid-based purified diet on intestinal mucosal integrity in cats with methotrexate-induced enteritis. Am. J. Vet. Res. 60, 755 (1999)
  9. Fox, A. D., Kripke, S. A., De Paula, J., Berman, J. M., Settle, R. G. and Rombeau, J. L. : Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis. JPEN J. Parenter. Enteral. Nutr. 12, 325 (1988)
  10. Kanauchi, O., Mitsuyama, K., Saiki, T., Agata, K., Nakamura, T. and Iwanaga, T. : Preventive effects of germinated barley foodstuff on methotrexate-induced enteritis in rats. Int. J. Mol. Med. 1, 961 (1998)
  11. Passos de Jesus Mazza, R., Bertevello, P. L., Matos de Miranda Torrinhas, R., Nonogaki, S., Avancini Ferreira Alves, V., Gama Rodrigues, J. and Waitzberg, D. L. : Effect of glutamine dipeptide on hepatic regeneration in partially hepatectomized malnourished rats. Nutrition 19, 930 (2003) https://doi.org/10.1016/S0899-9007(03)00177-1
  12. de Urbina, J. J., Jorquera, F., Culebras, J. M., Villares, C., Gonzalez-Gallego, J. and Tunon, M. J. : Effects of parenteral nutrition supplemented with alanyl-glutamine on nutrition status in rats. JPEN J. Parenter. Enteral Nutr. 29, 262 (2005) https://doi.org/10.1177/0148607105029004262
  13. 김은정, 김정욱 : Diclofenac에 의해 유발된 장내세균전위와 지 질과산화에 대한 글루타민의 효과. 약학회지 49, 128 (2005)
  14. McBurney, M. W. and Whitmore, G. F. : Mechanism of growth inhibition by methotrexate. Cancer Res. 35, 586 (1975)
  15. Moell, C. and Garwicz, S. : High-dose methotrexate causes short-term suppression of growth in rabbits. Acta. Paediatr. 84, 1237 (1995)
  16. Iqbal, M. P., Ahmed, M., Umer, M., Mehboobali, N. and Qureshi, A. A. : Effect of methotrexate and folinic acid on skeletal growth in mice. Acta. Paediatr. 92, 1438 (2003) https://doi.org/10.1080/08035250310006890
  17. Miller, A. L. : Therapeutic considerations of L-glutamine: a review of the literature. Altern. Med. Rev. 4, 239 (1999)
  18. Buchman, A. L. : Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data. Am. J. Clin. Nutr. 74, 25 (2001)
  19. Kudsk, K. A., Wu, Y., Fukatsu, K., Zarzaur, B. L., Johnson, C. D., Wang, R. and Hanna, M. K. : Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels. J. Parenter. Enteral. Nutr. 24, 270 (2000)
  20. Ueda, Y., Saito, A., Fukuoka, Y., Yamashiro, Y., Ikeda, Y., Taki, H., Yasuda, T. and Saikawa, I. : Interactions of beta-lactam antibiotics and antineoplastic agents. Antimicrob. Agents Chemother. 23, 374 (1983)
  21. Michel, J., Jacobs, J. Y. and Sacks, T. : Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against gram-negative bacilli. Antimicrob. Agents Chemother. 16, 761 (1979)
  22. Kim, E. J. and Kim, J. W. : The changes of non-steroidal antiinflammatory drug induced gut damage, bacterial overgrowth, bacterial translocation and organ weights in rat model. Intestinal Research 4, 45 (2006)
  23. Berg, R. D. : Bacterial translocation from the gastrointestinal tract. Adv. Exp. Med. Biol. 473, 11 (1999)
  24. Pardo, A., Bartoli, R., Lorenzo-Zuniga, V., Planas, R., Vinado, B., Riba, J., Cabre, E., Santos, J., Luque, T., Ausina, V. and Gassull, M. A. : Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis. Hepatology 31, 858 (2000)