Pro-inflammatory response markers and neutrophil activity index of mice treated with butaphosphan and challenged with bacterial endotoxin

Authors

DOI:

https://doi.org/10.33448/rsd-v11i10.32386

Keywords:

Organic phosphorus; Cellular immunity; Lipopolysaccharide; Neutrophil; IL-6; IL-1β.

Abstract

Butaphosphan, an organic source of phosphorus, potentiates humoral and cellular immune responses, however, it is still not clear how this occurs. We evaluate the effect of subcutaneous administration of injectable butaphosphan on pro-inflammatory markers and neutrophil activity index of mice challenged with bacterial lipopolysaccharide. Forty-two mice were randomly divided into three groups: Butaphosphan 50 (BUT50, n=14), that received injections of 50 mg/kg of butaphosphan; Butaphosphan 200 (BUT200, n=14), that received injections of 200 mg/kg of butaphosphan and Control (CTL, n=15), that received placebo. Subcutaneous injections were performed twice daily, for eight consecutive days. At the 8th day, half of animals per group were randomly selected to be challenged with bacterial lipopolysaccharide. Two hours after the challenge animals were euthanized, blood and spleen collected to analyze hematological parameters, circulating levels of interleukin 6 (IL-6), 1β (IL-1B) and myeloperoxidase (MPO) tissue activity. Red blood cell count was higher in butaphosphan treated groups. White blood cell count was lower in BUT200/LPS, as consequence of the decreased neutrophil count. Defense cells and IL-6 were elevated in BUT200 group. The use of butaphosphan ameliorate inflammatory markers, both in challenged and not challenged animals.

Author Biography

Marcio Nunes Corrêa, Universidade Federal de Pelotas

Médico Veterinário, com mestrado em Zootecnia e doutorado em Biotecnologia pela Universidade Federal de Pelotas (UFPel). Atualmente é Professor Titular de Clínica Médica de Grandes Animais, no Departamento de Clínicas Veterinária da Faculdade de Veterinária-UFPel trabalhando com Ruminantes, em especial bovinos leiteiros. É bolsista de produtividade em pesquisa do CNPq desenvolvendo atividades direcionadas ao estudo do Metabolismo Animal, com ênfase em Interações entre Nutrição e Reprodução, Doenças Metabólicas e Desenvolvimento de Fármacos e produtos para Nutrição Animal. Orienta nos Programas de Pós-graduação em Veterinária e Biotecnologia e co-orienta no Programa de Zootecnia. Coordena o NUPEEC, Núcleo de Pesquisa, Ensino e Extensão em Pecuária, da UFPel. Foi Coordenador do Programa de Pós-Graduação em Veterinária (mestrado e doutorado), Diretor de Pós-Graduação e também Diretor de Pesquisa da UFPel, junto a Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação. Também Chefe do Departamento de Clínicas Veterinárias da Faculdade de Veterinária. Tem atuação como consultor em gestão de pessoas e de processos produtivos, inovação tecnológica e formação de profissionais. Atualmente desenvolve atividades de mentoria para 5 Startups e de tutoria para 2 empreendimentos, todos vinculados à UFPel.

References

Berndt, T., & Kumar, R. 2009. Novel mechanisms in the regulation of phosphorus homeostasis. Physiology (Bethesda) 24:17-25.10.1152/physiol.00034.2008.

Berg, J. M., J. L. Tymoczko, & Stryer, L. 2006. Glycolysis and gluconeogenesis. In Biochemistry, eds. J.M. Berg, and J.L. Tymoczko, and L. Stryer, 433-474. Freemand and co.

Brinkmann, V., U. Reichard, C. Goosmann, B. Fauler, Y. Uhlemann, D. S. Weiss, Y. Weinrauch, & Zychlinsky, A. 2004. Neutrophil extracellular traps kill bacteria. Science 303 (5663):1532-1535.10.1126/science.1092385.

Camalier, C. E., M. Yi, L. R. Yu, B. L. Hood, K. A. Conrads, Y. J., Lee, Lin, Y., et al. 2013. An integrated understanding of the physiological response to elevated extracellular phosphate. J Cell Physiol 228 (7):1536-1550.10.1002/jcp.24312.

Coppo, J. A., & Gapel, E. R. 2000. Results of using Catosal® B12 to treat racehorses in Argentina. A Hora Veterinária 19 (113):3.

Copeland, S., H. S. Warren, S. F. Lowry, S. E. Calvano, & Remick, D. 2005. Acute inflammatory response to endotoxin in mice and humans. Clin Diagn Lab Immunol 12 (1):60-67.12/1/60 [pii].

Cunningham, J. G. 2002. Textbook of Veterinary Physiology. (3rd )Aufl. Philadelphia: W.B. Saunders,.

Craddock, P. R., Y., Yawata, L., VanSanten, S., Gilberstadt, S., Silvis, & Jacob. H. S. 1974. Acquired phagocyte dysfunction. A complication of the hypophosphatemia of parenteral hyperalimentation. N Engl J Med 290 (25):1403-1407.10.1056/NEJM197406202902504.

Dantzer, R. 2004. Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 500 (1-3):399-411.:S0014-2999(04)00749-6 [pii].

Deniz, A., U., Spiecker-Hauser, & Rehagen. M. 2009. Efficacy of a butafosfan and vitamin B12 combination (Catosal®) on biochemical and hematological blood parameters in dogs treated with dexamethasone. The International Journal of Applied Research in Veterinary Medicine 7 (3):14.

Dinarello, C. A. 2009. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519-550.10.1146/annurev.immunol.021908.132612.

Furll, M., A. Deniz, B. Westphal, C. Illing, & Constable, P. D. 2010. Effect of multiple intravenous injections of butaphosphan and cyanocobalamin on the metabolism of periparturient dairy cows. J Dairy Sci 93 (9):4155-4164. doi:10.3168/jds.2009-2914.

Ganeshan, K., & Chawla, A. 2014. Metabolic regulation of immune responses. Annu Rev Immunol 32:609-634.10.1146/annurev-immunol-032713-120236.

González, F. H. D., & Silva, S. C. (2019). Minerais e vitaminas no metabolismo animal: Laboratório de análises clínicas, Faculdade de veterinária, UFRGS.

Guerrini, M. M., & Takayanagi, H. 2014. The immune system, bone and RANKL. Arch Biochem Biophys 561:118-123.10.1016/j.abb.2014.06.003.

Grunberg, W. 2014. Treatment of phosphorus balance disorders. Vet Clin North Am Food Anim Pract 30 (2):383-408, vi.10.1016/j.cvfa.2014.03.002.

Ha, S., X.Y. Du, J. Jiang, & B. Zhu. 2005. Study on immune stimulating properties of compound butafosfan solution in mice. Chinese Journal of Veterinary Science and Technology, (7):5.

Hirano, T., Akira, S., Taga, T., & Kishimoto, T. 1990. Biological and clinical aspects of interleukin 6. Immunol Today 11 (12):443-449.

Júnior, A. O. M., de Melo Mota, L., & Ramos, M. T. B. P. (2018). Imunologia essencial. Gramma.

Karlen, J. 1989. Renal response to low and high phosphate intake in weanling, adolescent and adult rats. Acta Physiol Scand 135 (3):317-322.10.1111/j.1748-1716.1989.tb08583.x.

Kaplanski, G., V. Marin, F. Montero-Julian, A. Mantovani, & Farnarier, C. 2003. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24 (1):25-29.S1471490602000133 [pii].

Katsumata, S., Masuyama, R., Uehara, M., & Suzuki, K. 2004. Decreased mRNA expression of the PTH/PTHrP receptor and type II sodium-dependent phosphate transporter in the kidney of rats fed a high phosphorus diet accompanied with a decrease in serum calcium concentration. Biosci Biotechnol Biochem 68 (12):2484-2489. JST.JSTAGE/bbb/68.2484 [pii].

Kegley, E. B., Spears, J. W., & Auman, S. K. 2001. Dietary phosphorus and an inflammatory challenge affect performance and immune function of weanling pigs. J Anim Sci 79 (2):413-419.

Kennedy, D. G., Cannavan, A., Molloy, A., O'Harte, F., Taylor, S. M., Kennedy, S., & Blanchflower, W. J. 1990. Methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (EC 2.1.1.13) in the tissues of cobalt-vitamin B12 deficient sheep. Br J Nutr 64 (3):721-732. S0007114590001490 [pii].

Kiersztejn, M., Chervu, I., Smogorzewski, M., Fadda, G. Z., Alexiewicz, J. M., & Massry, S. G. 1992. On the mechanisms of impaired phagocytosis in phosphate depletion. J Am Soc Nephrol 2 (10):1484-1489.

Kothari, N., Keshari, R. S., Bogra, J., Kohli, M., Abbas, H., Malik, A., Dikshit, M., & Barthwal, M. K. 2011. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care 26 (4):435 e431-437.10.1016/j.jcrc.2010.09.001

Landsman, A., Lichtstein, D., Bacaner, M., & Ilani, A. 2001. Dietary phosphate-dependent growth is not mediated by changes in plasma phosphate concentration. Br J Nutr 86 (2):217-223.

Landsman, A., Lichtstein, D., & Ilani, A. 2005. Distinctive features of dietary phosphate supply. J Appl Physiol (1985) 99 (3):1214-1219.00095.2005 [pii].

Lima, M. E. 2014. Efeito do butafosfan e cianocobalamina sobre a produção de oócitos e embriões in vitro de vacas Jersey. Dissertação de Mestrado, Universidade Federal de Pelotas, Pelotas.

Massry, S. G., S. M. Hajjar, P. Koureta, G. Z. Fadda, & Smogorzewski, M. 1991. Phosphate depletion increases cytosolic calcium of brain synaptosomes. Am J Physiol 260 (1 Pt 2):F12-18.

Metzler, K. D., T. A. Fuchs, W. M. Nauseef, D. Reumaux, J. Roesler, I. Schulze, V. Wahn, V. Papayannopoulos, & Zychlinsky, A. 2011. Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood 117 (3):953-959. doi:10.1182/blood-2010-06-290171.

Mullarky, I. K., W. A. Wark, M. Dickenson, S. Martin, C. S. Petersson-Wolfe, & K. F. Knowlton. 2009. Short communication: analysis of immune function in lactating dairy cows fed diets varying in phosphorus content. J Dairy Sci 92 (1):365-368. doi:10.3168/jds.2008-1323.

Morimoto, A., T. Nakamori, T. Watanabe, T. Ono, & N. Murakami. 1988. Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins. Am J Physiol 254 (4 Pt 2):R633-640.

Pulli, B., M. Ali, R. Forghani, S. Schob, K. L. Hsieh, G. Wojtkiewicz, J. J. Linnoila, & J. W. Chen. 2013. Measuring myeloperoxidase activity in biological samples. PLoS One 8 (7):e67976. doi:10.1371/journal.pone.0067976.

Pereira, R. A., S. Fensterseifer, V. B. Barcelos, C. F. Martins, A. Schneider, E. Schmitt, L. F. Pfeifer, F. A. Del Pino, & M. N. Correa. 2013. Metabolic parameters and dry matter intake of ewes treated with butaphosphan and cyanocobalamin in the early postpartum period. Small Ruminant Research 114:6.

Pereira, R. A., P. A. Silveira, P. Montagner, A. Schneider, E. Schmitt, V. R. Rabassa, L. F. Pfeifer, F. A. Del Pino, M. E. Pulga, & M. N. Correa. 2013. Effect of butaphosphan and cyanocobalamin on postpartum metabolism and milk production in dairy cows. Animal 7 (7):1143-1147.10.1017/S1751731113000013.

Pizoni. C., Izquierdo, V., Klaus, R., Santos, E. Dos., Vieira, L. V, Barbosa, A. A., Cardoso, K., Velasquez, B., Del Pino, F., Rabassa, V., Brauner, C., &Corrêa, M. N. 2022. Uso de Butafosfano com Cianocobalamina em Vacas de Alta Produção e Associações com Rendimento de Leite e Consumo de Matéria Seca. Pesquisa, Sociedade e Desenvolvimento , [S. l.] , 11(4), pág. e48311427045. 10.33448/rsd-v11i4.27045.

Portale, A. A., B. P. Halloran, & R. C. Morris, Jr. 1987. Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus. Implications for the renal production of 1,25-dihydroxyvitamin D. J Clin Invest 80 (4):1147-1154.10.1172/JCI113172.

Queen, A. E., M. Moerdyk-Schauwecker, L. M. McKee, L. J. Leamy, & Y. M. Huet. 2016. Differential Expression of Inflammatory Cytokines and Stress Genes in Male and Female Mice in Response to a Lipopolysaccharide Challenge. PLoS One 11 (4):e0152289.10.1371/journal.pone.0152289

Rollin, E., R. D. Berghaus, P. Rapnicki, S. M. Godden, & M. W. Overton. 2010. The effect of injectable butaphosphan and cyanocobalamin on postpartum serum beta-hydroxybutyrate, calcium, and phosphorus concentrations in dairy cattle. J Dairy Sci 93 (3):978-987.10.3168/jds.2009-2508

Reece, W. O. 2007. Dukes - Fisiologia dos Animais Domésticos. 12ª Aufl. Guanabara Koogan.

Romanovsky, A. A., V. A. Kulchitsky, N. V. Akulich, S. V. Koulchitsky, C. T. Simons, D. I. Sessler, & V. N. Gourine. 1996. First and second phases of biphasic fever: two sequential stages of the sickness syndrome? Am J Physiol 271 (1 Pt 2):R244-253.

Segal, A. W. 2005. How neutrophils kill microbes. Annual Review of Immunology 23:30.

Schneiders, J., F. Fuchs, J. Damm, C. Herden, R. Gerstberger, D. M. Soares, J. Roth, & C. Rummel. 2015. The transcription factor nuclear factor interleukin 6 mediates pro- and anti-inflammatory responses during LPS-induced systemic inflammation in mice. Brain Behav Immun 48:147-164.10.1016/j.bbi.2015.03.008.

Shah, B. G., G. V. Krishnarao, & H. H. Draper. 1967. The relationship of Ca and P nutrition during adult life and osteoporosis in aged mice. J Nutr 92 (1):30-42.

Skelly, D. T., E. Hennessy, M. A. Dansereau, & C. Cunningham. 2013. A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1beta, [corrected] TNF-alpha and IL-6 challenges in C57BL/6 mice. PLoS One 8 (7):e69123.10.1371/journal.pone.0069123.

Skelly, D. T., E. Hennessy, M. A. Dansereau, & C. Cunningham. 2013. A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1beta, [corrected] TNF-alpha and IL-6 challenges in C57BL/6 mice. PLoS One 8 (7):e69123.10.1371/journal.pone.0069123.

Tabeleão, V.C., R. A. Pereira, R.F. Prietsch, J.O. Feijó, C. Bondan, P. Mattei, E. Schmitt, F. A. del Pino, & M. N. Correa. 2016. Butafosfan e cianocobalamina: efeitos indiretos na recuperação da glândula mamária de vacas leiteiras após mastite clínica. Science and Animal Health 4 (3):17.

Tani, Y., T. Sato, H. Yamanaka-Okumura, H. Yamamoto, H. Arai, N. Sawada, K. Genjida, Y. Taketani, & E. Takeda. 2007. Effects of prolonged high phosphorus diet on phosphorus and calcium balance in rats. J Clin Biochem Nutr 40 (3):221-228.10.3164/jcbn.40.221.

Talmage, R. V., & H. T. Mobley. 2008. Calcium homeostasis: reassessment of the actions of parathyroid hormone. Gen Comp Endocrinol 156 (1):1-8.S0016-6480(07)00389-9 [pii]

Takeda, E., H. Yamamoto, H. Yamanaka-Okumura, & Y. Taketani. 2012. Dietary phosphorus in bone health and quality of life. Nutr Rev 70 (6):311-321.10.1111/j.1753-4887.2012.00473.x.

Takayanagi, H. 2007. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7 (4):292-304. doi:nri2062 [pii].

Takayanagi, H. 2007. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7 (4):292-304. doi:nri2062 [pii].

Temizel, E.M., H. Batmaza, A. Keskin, A. Orman, H. Gencoglu, S. Catik, & O. Topala. 2015. Butaphosphan and cyanocobalamin treatment of pregnant ewes: Metabolic effects and potential prophylactic effect for pregnancy toxaemia. Small Ruminant Research 125:10.

Yawata, Y., R. P. Hebbel, S. Silvis, R. Howe, & H. Jacob. 1974. Blood cell abnormalities complicating the hypophosphatemia of hyperalimentation: erythrocyte and platelet ATP deficiency associated with hemolytic anemia and bleeding in hyperalimented dogs. J Lab Clin Med 84 (5):643-653.0022-2143(74)90140-1 [pii].

Zhou, X. J., G. Z. Fadda, A. F. Perna, & S. G. Massry. 1991. Phosphate depletion impairs insulin secretion by pancreatic islets. Kidney Int 39 (1):120-128.S0085-2538(15)57096-8 [pii].

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23/07/2022

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MATTEI , P. .; JACOMETO, C. B.; PEREIRA, R. A. .; MONTAGNER, P.; WEILLER , M. A. A.; TEIXEIRA, R. dos S. .; CORRÊA, M. N. Pro-inflammatory response markers and neutrophil activity index of mice treated with butaphosphan and challenged with bacterial endotoxin. Research, Society and Development, [S. l.], v. 11, n. 10, p. e72111032386, 2022. DOI: 10.33448/rsd-v11i10.32386. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/32386. Acesso em: 4 oct. 2022.

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Agrarian and Biological Sciences