Effects of supplementing the amino acid L-Citrulline on experimental infection with Leishmania infantum (Syn. L. chagasi)
DOI:
https://doi.org/10.21527/2176-7114.2024.49.15694Keywords:
Visceral leishmaniasis, Nutraceuticals, AnthropometryAbstract
Background: Leishmania infantum is the etiologic agent of visceral leishmaniasis, a disease that affects millions of people around the world. This study explores the therapeutic potential of supplementing the amino acid L-Citrulline in modulating the immune response and attenuating the progression of this disease in murine models. Methods: The study animals (isogenic BALB/c mice) were divided into two groups: Group A - supplementation started 7 days before infection; Group B - supplementation started on the first day of infection. Supplementation in both groups took place over 7 uninterrupted days with a dosage of 0.03g of the amino acid dissolved in 0.4mL of saline solution. Experimental infection occurred with the intraperitoneal inoculation of 1x106 L. infantum promastigotes. The mice's body weight was measured by the same evaluator every 7 days, from the start of the experiment until euthanasia (8th day of infection). The other parameters were assessed after the animals were euthanized. The values were tabulated and statistically analyzed. Results: L-Citrulline supplementation resulted in a higher percentage of body weight gain in both infected and uninfected animals during the periods analyzed. In the group treated synchronously with the infection, the infected animals showed significant weight gain when compared to those given saline solution. Conclusion: L-Citrulline supplementation may be a promising nutritional strategy during the treatment of L. infantum infection, so it is interesting to evaluate the effects of using this amino acid in humans and in other hypercatabolic diseases.
References
Shaw JJ. New World Leishmaniasis: The Ecology of Leishmaniasis and the Diversity of Leishmanial Species in Central and South America. Em: Farrell JP, organizador. Leishmania [Internet]. Boston, MA: Springer US; 2002 [citado 26 de setembro de 2023]. p. 11–31. (World Class Parasites). Disponível em: https://doi.org/10.1007/978-1-4615-0955-4_2
Rangel EF, Vilela ML. Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae) and urbanization of visceral leishmaniasis in Brazil. Cad Saúde Pública. dezembro de 2008;24:2948–52.
Brazil RP. The dispersion of Lutzomyia longipalpis in urban areas. Rev Soc Bras Med Trop. junho de 2013;46:263–4.
Lainson R, Rangel EF. Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil: a review. Mem Inst Oswaldo Cruz. dezembro de 2005;100:811–27.
Brasil. Situação epidemiológica da Leishmaniose Visceral [Internet]. Ministério da Saúde. 2023 [citado 14 de fevereiro de 2024]. Disponível em: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/l/leishmaniose-visceral/situacao-epidemiologica-da-leishmaniose-visceral/situacao-epidemiologica-da-leishmaniose-visceral
Brasil - Ministério da Saúde. Guia de Vigilância em Saúde [Internet]. Brasilia: Ministério da saúde; 2019 p. 740. Disponível em: https://portalarquivos2.saude.gov.br/images/pdf/2019/junho/25/guiavigilancia- saude-volume-unico-3ed.pdf
Costa CHN, Chang KP, Costa DL, Cunha FVM. From Infection to Death: An Overview of the Pathogenesis of Visceral Leishmaniasis. Pathogens. 24 de julho de 2023;12(7):969.
Oliveira AGL. Evolução do estado nutricional e caracterização do padrão alimentar de pacientes com leishmaniose tegumentar americana [Internet] [tese]. [Rio de Janeiro]: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz; 2018. Disponível em: https://www.arca.fiocruz.br/handle/icict/37727
Katona P, Katona-Apte J. The Interaction between Nutrition and Infection. Clinical Infectious Diseases. 15 de maio de 2008;46(10):1582–8.
PAHO/WHO, Pan American Health Organization. OMS lança primeiro relatório mundial sobre prevenção e controle de infecções - OPAS/OMS | Organização Pan-Americana da Saúde [Internet]. 2022 [citado 19 de fevereiro de 2024]. Disponível em: https://www.paho.org/pt/noticias/6-5-2022-oms-lanca-primeiro-relatorio-mundial-sobre-prevencao-e-controle-infeccoes
Coelho LF. Análise morfológica do fígado e baço de camundongos Balb/c submetidos à desnutrição protéico-calórica e infectados com Leishmania infantum. [Internet] [Dissertação]. [Ouro Preto]: Universidade Federal de Ouro Preto; 2011. Disponível em: http://www.repositorio.ufop.br/jspui/handle/123456789/3212
Aguiar PF, Rodrigues RK. Leishmaniose Visceral no Brasil: Artigo de Revisão. Revista Unimontes Científica. 2017;19(1):192–204.
Maio R, Dichi JB, Burini RC. Conseqüências nutricionais das alterações metabólicas dos macronutrientes na doença hepática crônica. Arq Gastroenterol. janeiro de 2000;37:52–7.
Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, et al. Almost all about citrulline in mammals. Amino Acids. 1o de novembro de 2005;29(3):177–205.
Batista MA. Efeitos da L-citrulina no processo de translocação bacteriana e na permeabilidade intestinal em modelo experimental de obstrução intestinal [Internet] [Dissertação]. [Minas Gerais]: Universidade Federal de Minas Gerais; 2010. Disponível em: http://hdl.handle.net/1843/MBSA-8FMMFL
Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab. setembro de 2006;291(3):E582-586.
Bar-Peled L, Sabatini DM. Regulation of mTORC1 by amino acids. Trends Cell Biol. julho de 2014;24(7):400–6.
Goron A, Plénier S, Archambault E, Cynober L, Moinard C. Citrulline activates S6K1 and 4E-BP1 in muscle cells by both mTORC1-dependent and mTORC1-independent pathways. Clin Nutr Suppl 32:S118. Clinical Nutrition. 1o de setembro de 2013;32:S118.
Pagliarone AC, Sforcin JM. Estresse: revisão sobre seus efeitos no sistema imunológico. Biosaúde. 2009;11(1):57–90.
Cunha HFR da, Rocha EEM da, Hissa M. Necessidades proteicas, morbidade e mortalidade no paciente grave: fundamentos e atualidades. Rev bras ter intensiva. março de 2013;25:49–55.
Novaes MRCG, Pantaleão C de M. Arginina: bioquímica, fisiologia e implicações terapêuticas em pacientes com câncer gastrointestinal. Revista de Ciências Médicas [Internet]. 2005 [citado 19 de fevereiro de 2024];14(1). Disponível em: https://periodicos.puc-campinas.edu.br/cienciasmedicas/article/view/1195
Crenn P, Cynober L. Effect of intestinal resections on arginine metabolism: practical implications for nutrition support. Curr Opin Clin Nutr Metab Care. janeiro de 2010;13(1):65–9.
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