Vol. 23 No. 1 (2021)
Original articles

Glutamine increases body weight and decreases myocardial damage in Trypanosoma cruzi-infected mice treated with nifurtimox

Carmen Luisa Marín Tello
Universidad Nacional de Trujillo
César Sánchez-Marín
Universidad Nacional de Trujillo
Luis Arteaga-Temoche
Universidad Nacional de Trujillo

Published 2021-01-15

Keywords

  • Cardiovascular systems,
  • Tropical disease,
  • Nutrition policy.

How to Cite

Marín Tello, C. L., Sánchez-Marín, C. ., & Arteaga-Temoche, L. . (2021). Glutamine increases body weight and decreases myocardial damage in Trypanosoma cruzi-infected mice treated with nifurtimox. Revista De Investigaciones Altoandinas - Journal of High Andean Research, 23(1), 10-16. https://doi.org/10.18271/ria.2021.210

Abstract

Chagas disease, a parasitic infection caused by the protist Trypanosoma cruzi, affects the poorest populations, living in remote, rural areas and urban slums. Although this drug is effective against Chagas disease it presents a number of serious side effects. In residents of high Andean areas with megacolon it can lead to cardiomyopathies. The aim of this study was to investigate whether dietary supplementation with L-glutamine may alleviate some of these symptoms because of its previously observed anti-inflammatory properties. We studied two groups of T. cruzi-infected mice receiving treatment with nifurtimox. One group was fed the standard diet, while the other group’s diet was supplemented with Glutamine. We found that Glutamine supplementation increases body weight (p<0.001), decreases heart-mass-to-body-mass ratio (p<0.001), and decreases the number of amastigotes present in cardiac tissue. Additionally, histopathological analysis showed less heart tissue damage in the group that received Glutaminne in their diet. Therefore, our findings suggest that Glutamine supplementation improves nifurtimox treatment outcomes of T. cruzi infection.

References

  1. Almeida, E. B., Santos, J., Paixão, V., Amaral, J. B., Foster, R., Sperandio, A., Roseira, T., Rossi, M., Cordeiro, T. G., Monteiro, F. R., Amirato, G. R., Santos, C., Vieira, R. P., Vaisberg, M., Barros, M. P., & Bachi, A. (2020). L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals. Oxidative Medicine and Cellular Longevity, 2020(di). https://doi.org/10.1155/2020/2852181
  2. Bayona-caballero, M., Alayo-zavaleta, J., Lombardi-pérez, C., & Marín-tello, C. (2019). The radioprotective effect of a wheat germ diet on rat myocardial tissue exposed to X-rays. Ars Pharmaceutica, 60(4), 213–218. https://doi.org/10.30827/ars.v60i4.10226
  3. C de Oliveira, D., Santos, E. W., Nogueira-Pedro, A., Xavier, J. G., Borelli, P., & Fock, R. A. (2018). Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties. Nutrition, 48, 96–104. https://doi.org/10.1016/j.nut.2017.11.015
  4. Cabanillas Stanchi, K. M., Bruchelt, G., Handgretinger, R., & Holzer, U. (2015). Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma. Cancer Biology & Therapy, 16(9), 1353–1363. https://doi.org/10.1080/15384047.2015.1070987
  5. Camargo, M. E. (1966). Fluorescent antibody test for the serodiagnosis of American trypanosomiasis. Technical modification employing preserved culture forms of Trypanosoma cruzi in a slide test. Revista Do Instituto de Medicina Tropical de Sao Paulo, 8(5), 227–235. https://europepmc.org/article/med/4967348
  6. Chatelain, E. (2017). Chagas disease research and development: Is there light at the end of the tunnel? Computational and Structural Biotechnology Journal, 15, 98–103. https://doi.org/10.1016/j.csbj.2016.12.002
  7. Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018). Glutamine: Metabolism and immune function, supplementation and clinical translation. Nutrients, 10(11), 1–31. https://doi.org/10.3390/nu10111564
  8. de Urbina, J., San-Miguel, B., Vidal-Casariego, A., Crespo, I., Sánchez, D. I., Mauriz, J. L., Culebras, J. M., González-Gallego, J., & Tuñón, M. J. (2017). Effects Of Oral Glutamine on Inflammatory and Autophagy Responses in Cancer Patients Treated With Abdominal Radiotherapy: A Pilot Randomized Trial. International Journal of Medical Sciences, 14(11), 1065–1071. https://doi.org/10.7150/ijms.20245
  9. Doevendans, P. A., Daemen, M. J., De Muinck, E. D., & Smits, J. F. (1998). Cardiovascular phenotyping in mice. Cardiovascular Research, 39(1), 34–49. https://doi.org/10.1016/S0008-6363(98)00073-X
  10. Escobar, F., Ferro, Mayhua, F., Rocha, N., & León, M. (2020). Seminario Internacional “resistencia a antibióticos”: Amenaza global a la salud pública - Universidad Nacional del Altiplano, Puno Perú. Revista de Investigaciones Altoandinas, 22(1), 7-24. https://dx.doi.org/10.18271/ria.2020.529.
  11. Fathi, H., Mowafy, S., & Helmy, K. (2018). Evaluation of the effectiveness of glutamine in different times of administration in patients undergoing cardiopulmonary bypass during elective cardiac surgeries: randomized controlled study. The Egyptian Journal of Cardiothoracic Anesthesia, 12(1), 4. https://doi.org/10.4103/ejca.ejca_4_16
  12. Flores-Ferrer, A., Marcou, O., Waleckx, E., Dumonteil, E., & Gourbière, S. (2017). Evolutionary ecology of Chagas disease; what do we know and what do we need? Evolutionary Applications, (April 2017), 470–487. https://doi.org/10.1111/eva.12582
  13. Freire, A., Alves, C. L., Goes, G. R., Resende, B. C., Moretti, N. S., Nunes, V. S., Aguiar, P., Tahara, E. B., Franco, G. R., Macedo, A. M., Pena, S., Gadelha, F. R., Guarneri, A. A., Schenkman, S., Vieira, L. Q., & Machado, C. R. (2017). Catalase expression impairs oxidative stress-mediated signalling in Trypanosoma cruzi. Parasitology, 144(11), 1498–1510. https://doi.org/10.1017/S0031182017001044
  14. Frisancho, E. (2008). Dolicomegacolon andino y vólvulos intestinales de altura. Revista de Gastroenterología Del Perú, 28(3), 248–257. http://repebis.upch.edu.pe/cgi-bin/wxis.exe/iah/scripts/?IsisScript=iah.xis&lang=es&base=lipecs&nextAction=lnk&exprSearch=MEGACOLON&indexSearch=MH
  15. Gaspar, L., Moraes, C. B., Freitas-Junior, L. H., Ferrari, S., Costantino, L., Costi, M. P., Coron, R. P., Smith, T. K., Siqueira-Neto, J. L., McKerrow, J. H., & Cordeiro-da-Silva, A. (2015). Current and Future Chemotherapy for Chagas Disease. Current Medicinal Chemistry, 22(37), 4293–4312. https://doi.org/10.2174/0929867322666151015120804
  16. Hill, A., Nesterova, E., Lomivorotov, V., Efremov, S., Goetzenich, A., Benstoem, C., Zamyatin, M., Chourdakis, M., Heyland, D., & Stoppe, C. (2018). Current evidence about nutrition support in cardiac surgery patients—what do we know? Nutrients, 10(5). https://doi.org/10.3390/nu10050597
  17. Houweling, T. A., Karim-Kos, H. E., Kulik, M. C., Stolk, W. A., Haagsma, J. A., Lenk, E. J., Richardus, J. H., & de Vlas, S. J. (2016). Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review. PLOS Neglected Tropical Diseases, 10(5), e0004546. https://doi.org/10.1371/journal.pntd.0004546
  18. Kracht, M., Müller-Ladner, U., & Schmitz, M. L. (2020). Mutual regulation of metabolic processes and proinflammatory NF-κB signaling. Journal of Allergy and Clinical Immunology, 1–12. https://doi.org/10.1016/j.jaci.2020.07.027
  19. Lidani, K. C. F., Andrade, F. A., Bavia, L., Damasceno, F. S., Beltrame, M. H., Messias-Reason, I. J., & Sandri, T. L. (2019). Chagas disease: From discovery to a worldwide health problem. Journal of Physical Oceanography, 49(6), 1–13. https://doi.org/10.3389/fpubh.2019.00166
  20. Marsé Milla, P. (2015). Sixth Jesus culebras’ lecture: glutamine and the critical patient: the end of an age? Nutricion Hospitalaria, 32(6), 2374–2379. https://doi.org/10.3305/nh.2015.32.6.10055
  21. Martinez, S. J., Romano, P. S., & Engman, D. M. (2020). Precision Health for Chagas Disease: Integrating Parasite and Host Factors to Predict Outcome of Infection and Response to Therapy. Frontiers in Cellular and Infection Microbiology, 10(May), 1–11. https://doi.org/10.3389/fcimb.2020.00210
  22. Nogueira, P. M., Ribeiro, K., Silveira, A. C., Campos, J. H., Martins-Filho, O. A., Bela, S. R., Campos, M. A., Pessoa, N. L., Colli, W., Alves, M. J., Soares, R. P., & Torrecilhas, A. C. (2015). Vesicles from different Trypanosoma cruzi strains trigger differential innate and chronic immune responses. Journal of Extracellular Vesicles, 4(1). https://doi.org/10.3402/jev.v4.28734
  23. Oliveira, S. R., Ariel, M.C., Silva., F.D. (2020). Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis in Trypanosoma cruzi molecules, 25, 1628; doi:10.3390/molecules25071628
  24. Pérez-Molina, J. A., Sojo-Dorado, J., Norman, F., Monge-Maillo, B., Díaz-Menéndez, M., Albajar-Viñas, P., & López-Vélez, R. (2013). Nifurtimox therapy for Chagas disease does not cause hypersensitivity reactions in patients with such previous adverse reactions during benznidazole treatment. Acta Tropica, 127(2), 101–104. https://doi.org/10.1016/J.ACTATROPICA.2013.04.003
  25. Qin, Q., Xu, X., Wang, X., Wu, H., Zhu, H., Hou, Y., Dai, B., Liu, X., & Liu, Y. (2018). Glutamate alleviates intestinal injury, maintains mTOR and suppresses TLR4 and NOD signaling pathways in weanling pigs challenged with lipopolysaccharide. Scientific Reports, 8(1), 2–11. https://doi.org/10.1038/s41598-018-33345-7
  26. Santos, A. C. A., Correia, C. A., de Oliveira, D. C., Nogueira-Pedro, A., Borelli, P., & Fock, R. A. (2016). Intravenous Glutamine Administration Modulates TNF-$α$/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model. Inflammation, 39(6), 1883–1891. https://doi.org/10.1007/s10753-016-0424-1
  27. Stehle, P., & Kuhn, K. S. (2015). Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy. BioMed Research International, 2015. https://doi.org/10.1155/2015/545467
  28. Urbina, J. A. (2018). The long road towards a safe and effective treatment of chronic Chagas disease. The Lancet Infectious Diseases, 18(4), 363–365. https://doi.org/10.1016/S1473-3099(17)30535-2
  29. Vaquerizo Alonso, C. (2017). Nutrición parenteral en el paciente crítico: indicaciones y controversias. Nutr Clin Med, XI, 26–41. https://doi.org/10.7400/NCM.2017.11.1.5048
  30. World Health Organization. (2020). Chagas disease (also known as American trypanosomiasis). World Health Organization. Geneva.Switzerland. Retrieved from https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)
  31. Wu, G., Hu, X., Ding, J., & Yang, J. (2020). The effect of glutamine on Dehydroepiandrosterone-induced polycystic ovary syndrome rats. Journal of Ovarian Research, 13(1), 1–7. https://doi.org/10.1186/s13048-020-00650-7
  32. Zhang, W. Bin, Zhang, H. Y., Zhang, Q., Jiao, F. Z., Zhang, H., Wang, L. W., & Gong, Z. J. (2017). Glutamine ameliorates lipopolysaccharide-induced cardiac dysfunction by regulating the toll-like receptor 4/mitogen-activated protein kinase/nuclear factor-κB signaling pathway. Experimental and Therapeutic Medicine, 14(6), 5825–5832. https://doi.org/10.3892/etm.2017.5324