La administración de NeuroEPO intranasal no afecta la estructura de la mucosa respiratoria en ratas Wistar
Palabras clave:
NeuroEPO, mucosa respiratoria, enfermedades neurodegenerativas, neuroprotección.Resumen
Introducción: Las enfermedades asociadas al Sistema Nervioso Central representan un grupo de padecimientos con importante repercusión social y económica. Las nuevas estrategias de tratamiento con NeuroEPO ofrecen nuevas oportunidades para prevenir la aparición y la progresión de estos desórdenes. La NeuroEPO administrada por vía intranasal puede alcanzar al Sistema Nervioso Central a través de varios mecanismos que involucran los nervios olfatorios y trigéminos, mucosa respiratoria y olfatoria, vasculatura nasal, fluido cerebroespinal y el sistema linfático.
Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO sobre la estructura histológica de la mucosa respiratoria y de su tejido linfático asociado en ratas Wistar.
Material y métodos: Se realizó un estudio experimental, descriptivo, longitudinal, prospectivo, utilizando la rata Wistar como modelo biológico. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. Uno de los grupos recibió NeuroEPO intranasal durante 28 días a dosis de 300 µg/ kg. Al otro grupo se le administró vehículo a una razón de 0,3µl /g. Se estudiaron las características histológicas de la mucosa respiratoria. Las medianas de los grupos fueron comparadas mediante la prueba U de Mann-Whitney.
Resultados: No se observaron alteraciones en las características histológicas de la mucosa respiratoria, ni del tejido linfático asociado a la mucosa nasal en ratas Wistar, tras la administración de la NeuroEPO.
Conclusión: La administración intranasal de NeuroEPO no provoca cambios patológicos sobre la estructura histológica de la mucosa respiratoria ni del tejido linfático asociado a la mucosa nasal de ratas Wistar en nuestras condiciones experimentales.
Descargas
Citas
1. Garzón F, Rodríguez Y, García JC, Rama R. Neuroprotective Effects of neuroEPO Using an In Vitro Model of Stroke. Behav Sci.2018;8(2):26.
2. Rama R, Garzón F, Rodríguez Cruz Y, Maurice T, García Rodríguez JC. Neuroprotective effect of Neuro-EPO in neurodegenerative diseases: “Aleajacta est.” Neural Regen Res [Online]. 2019 Sep [Cited 04/02/2022];14(9):1519. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557108/
3. Rey F, Balsari A, Giallongo T. Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases. ASN Neuro [Online]. 2019 [Cited 04/02/2022];11:1759091419871420. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712762/
4. Zucchella C, Sinforiani E, Tamburin S, Federico A, Mantovani E, Bernini S, et al. The Multidisciplinary Approach to Alzheimer'sDisease and Dementia. A Narrative Review of Non-Pharmacological Treatment. Front Neurol [Online]. 2018 Dec [Cited 04/02/2022];9:1058. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300511/
5. Fernández Romero T, Clapés Hernández S, Pérez Hernández CL, Barreto López JJ, Fernández Peña G. Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus. Rev haban cienc méd [Online]. 2022 [Cited 17/04/2022];21(1):e4617. Disponible en: http://www.revhabanera.sld.cu/index.php/rhab/article/view/4617
6. Ul Islam S, Shehzad A, Bilal Ahmed M, Lee YS. Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders. Molecules [Online]. 2020 Apr [Cited 04/02/2022];25(8):[Aprox. 2 p.]. Available from: https://pubmed.ncbi.nlm.nih.gov/32326318/
7. Fernández Romero T, Clapés Hernández S, Pérez CL, Núñez López N, Suárez Román G, Fernández G. Protective effect of NeuroEPO in the reproduction of diabetic rats. Rev haban cienc méd [Online]. 2022 [Cited 08/08/2022];21(4):[Aprox. 6 p.]. Available from : http://www.revhabanera.sld.cu/index.php/rhab/article/view/4797
8. Rodríguez Y, Strehaiano M, Rodríguez T, García JC, Maurice T. An intranasal formulation of erythropoietin (Neuro-EPO) prevents memory deficits and amyloid toxicity in the APPSwe transgenic mouse model of Alzheimer’s disease. J Alzheimer´s Dis [Online]. 2017;55(1):231-48. Available from: https://www.doi.org/10.3233/JAD-160500
9. Vega MLB, Shengnan L, Leon YR, Rodríguez AM, Fernández EC, Llano MG, et al. NeuroEPO improves cognition in Parkinson’s disease. Preliminary report. medRxiv [Online]. New York: medRxiv; 2022 [Cited 17/04/2022]. Available from: https://www.medrxiv.org/content/10.1101/2022.02.24.22271444v2
10. Pérez L, Sosa S, Valenzuela C, Bringas G, Urrutia N, Peñalver AI, et al. Clinical trial of neuroEPO in mild-to-moderate Alzheimer’s disease. Alzheimer's Dement [Online]. 2021;17:e050212. Available from: https://doi.org/10.1002/alz.050212
11. McCormick-Ell J, Connell N. Laboratory safety, biosecurity, and responsible animal use. ILAR journal [Online]. 2019;60(1):24-33. Available from: https://doi.org/10.1093/ilar/ilz012
12. Muñoz Cernada A, García Rodríguez JC, Núñez Figueredo Y, Pardo Ruiz Z, García Selman JD, Sosa Testé I, et al. Formulaciones nasales de EPOrh con bajo contenido de ácido siálico para el tratamiento de enfermedades del sistema nervioso central [Online]. La Habana; WO2007009404, 2007 [Cited 17/04/2022]. Available from: https://patentscope.wipo.int/search/es/detail.jsf?docId=WO2007009404
13. Tveden Nyborg P, Lykkesfeldt J. Animal Models in Pharmacology and Toxicology. In: Handbook of Laboratory Animal Science [Online]. Florida: CRC Press; 2021 [Cited 25/07/2022]. p. 665–94. Available from: https://www.taylorfrancis.com/chapters/edit/10.1201/9780429439964-30/animal-models-pharmacology-toxicology-pernille-tveden-nyborg-jens-lykkesfeldt
14. Uraih LC, Maronpot RR. Normal histology of the nasal cavity and application of special techniques. Environ Health Perspect [Online]. 1990;85:187-208. Available from: https://www.doi.org/10.1289/ehp.85-1568325
15. Young JT. Histopathologic examination of the rat nasal cavity. Fundam Appl Toxicol [Online]. 1981;1(4):309-12. Available from: https://www.doi.org/10.1016/s0272-0590(81)80037-1
16. Grada A, Mervis J, Falanga V. Research techniques made simple: animal models of wound healing. Journal of Investigative Dermatology [Online].2018;138(10):2095-105.e1. Available from: https://doi.org/10.1016/j.jid.2018.08.005
17. Verma A, Verma M, Singh A. Animal tissue culture principles and applications. Animal Biotechnology [Online]. 2020:269-93. Available from: http://www.doi.org/10.1016/B978-0-12-811710-1.00012-4
18. Abbas KA, Lichtman HA, Pillai S. Células y tejidos del sistema inmunitario. In: Inmunología celular y molecular. 7 ed. Barcelona: Elsevier Saunders; 2012.p.15-32.
19. Dan Wilcox, Brent Dove. UTHSCSA image tool (3.0) [Online]. USA: Informer Technologies, Inc; 2022 [Cited 25/07/2022]. Available from: https://imagetool.software.informer.com/Descargar-gratis/
20. Motulsky H, Chistopoulos A, Miller JR. Graphpad Prism Version 5.0 Software Inc, USA [Online]. San Diego: GraphPad; 2022 [Cited 25/07/2022]. Available from: http://www.graphpad.com
21. Suarez K, Fernández G, Rodriguez Y, Puldon G (2022), “Administration of intranasal NeuroEPO does not affect the structure of the respiratory mucosa in Wistar rats” [Online]. Amsterdam: Mendeley Data; 2022. Available from: http://doi.org/10.17632/c5zhgv532g.1
22. Jiang XZ, Buckley LA, Morgan KT. Pathology of toxic responses to the RD50 concentration of chlorine gas in the nasal passages of rats and mice. Toxicol Appl Pharmacol [Online]. 1983;71(2):225-36. Available from: http://www.doi.org/10.1016/0041-008x(83)90339-3
23. Harkema JR, Wagner JG. Innate Lymphoid Cell-Dependent Airway Epithelial and Inflammatory Responses to Inhaled Ozone: A New Paradigm in Pathogenesis. Toxicol Pathol [Online]. 2019;47(8):993-1003. Available from: http://www.doi.org/10.1177/0192623319873872
24. Edrissi B, Taghizadeh K, Moeller BC, Yu R, Kracko D, Doyle Eisele M, et al. N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats. Chem Res Toxicol [Online]. 2017;30(8):1572-6. Available from: http://www.doi.org/10.1021/acs.chemrestox.7b00075
25. Tesfaye S, Hamba N, Gerbi A, Negeri Z. Oxidative Stress and Carcinogenic Effect of Formaldehyde Exposure: Systematic Review & Analysis. Endocrinol Metab Syndr [Online]. 2020 Sep [Cited 04/02/2022];9(6):1-11. Available from: https://www.longdom.org/open-access/oxidative-stress-and-carcinogenic-effect-of-formaldehyde-exposure-systematic-review-analysis-58212.html
26. Eda A, Baver S, Seyla SB, Hüseyin Ö, Deveci E. Effects of Xylene on Respiratory Mucosa in Rats. Int J Morphol [Online]. 2016 Sep [Cited 04/02/2022];34(3):934-8. Available from: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022016000300019&lng=en&nrm=iso&tlng=en
27. Horak F, Zieglmayer UP, Zieglmayer R, Kavina A, Marschall K, Munzel U, et al. Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Curr Med Res Opin [Online]. 2006;22(1):151-7. Available from: http://www.doi.org/10.1185/030079906X80305
28. Small P, Keith PK, Kim H. Allergic rhinitis. Allergy Asthma Clin Immunol [Online]. 2018 [Cited 04/02/2022];14(2):1-11. Available from: https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0280-7
29. Lagarto A, Bueno V, Guerra I, Valdés O, Couret M, López R, et al. Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid. Exp Toxicol Pathol [Online]. 2011 [Cited 04/02/2022];63(6):563-7. Available from: https://pubmed.ncbi.nlm.nih.gov/20488687/
30. Rodríguez Cruz Y, Suárez Borrás K, Fernández Peña G, Puldón Seguí G. Efectos de la NeuroEPO sobre las características histológicas de la mucosa olfatoria en ratas wistar. En: Congreso MorfoVirtual 2020 [Online]. La Habana: Sociedad Cuabana de Ciencias Morfológicas; 2020 [Cited 25/07/2022]. Available from: http://www.morfovirtual2020.sld.cu/index.php/morfovirtual/morfovirtual2020/paper/view/25/
31. Marcondes de Godoy M, Lopes RA, Sala MA, Vinha D, Regalo SCH. Acción del Etanol sobre el Epitelio Nasal y Glándulas Septales de Ratas, Durante la Lactancia. Int J Morphol [Online]. 2005 [Cited 04/02/2022];23(4):293-300. Available from: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022005000400002&lng=es&nrm=iso&tlng=es
32. Alt JA, Qin X, Pulsipher A, Orb Q, Orlandi RR, Zhang J, et al. Topical cathelicidin (LL-37) an innate immune peptide induces acute olfactory epithelium inflammation in a mouse model. Int Forum Allergy Rhinol [Online]. 2015 Dec;5(12):1141-50. Available from: http://www.doi.org/10.1002/alr.21634
33. Chamanza R, Wright J. A review of the comparative anatomy, histology, physiology and pathology of the nasal cavity of rats, mice, dogs and non-human primates. Relevance to inhalation toxicology and human health risk assessment. Journal of Comparative Pathology [Online]. 2015;153(4):287-314. Available from: https://doi.org/10.1016/j.jcpa.2015.08.009
34. Elmore SA. Enhanced Histopathology Evaluation of Lymphoid Organs. Methods Mol Biol [Online]. 2018 [Cited 30/03/2022];1803:147-68. Available from: https://link.springer.com/protocol/10.1007/978-1-4939-8549-4_10
35. Elmore SA. Enhanced Histopathology of Mucosa-Associated Lymphoid Tissue. Toxicol Pathol [Online]. 2006 Jun [Cited 30/03/2022];34(5):687-96. Available from: https://journals.sagepub.com/doi/full/10.1080/01926230600939989
36. Frieke Kuper C, van Oostrum L, Ma-Hock L, Durrer S, Woutersen RA. Hyperplasia of the lymphoepithelium of NALT in rats but not in mice upon 28-day exposure to 15ppm formaldehyde vapor. Exp Toxicol Pathol [Online]. 2011;63(1):25-32. Available from: https://www.sciencedirect.com/science/article/pii/S0940299309002437
37. Marino JH, Teague TK. The Immune System as a Sensor and Regulator of Stress: Implications in Human Development and Disease. In: Biobehavioral Markers in Risk and Resilience Research [Online]. Switzerland: Springer; 2019. p. 1-11. Available from: https://doi.org/10.1007/978-3-030-05952-1_1
38. Kuper CF, Wijnands MVW, Zander SAL. Mucosa-Associated Lymphoid Tissues BT - Immunopathology in Toxicology and Drug Development. In: Parker GA, ed. Organ Systems [Online]. Switzerland: Springer International Publishing; 2017. p. 81-121. Available from: https://doi.org/10.1007/978-3-319-47385-7_4
39. Pacák K, Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev [Online]. 2001 Aug;22(4):502-48. Available from: http://www.doi.org/10.1210/edrv.22.4.0436
Descargar PDF
