medigraphic.com
ISSN 1729-519X (Print)

2022, Number 5

<< Back Next >>

Revista Habanera de Ciencias Médicas 2022; 21 (5)

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats

Suárez BK, Fernández PG, Puldón SG, Rodríguez CY, Pérez HCL

Language: English
References: 31
Page: 1-7
PDF size: 4603.51 Kb.


ABSTRACT

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally.
Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test.
Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO.
Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.


REFERENCES

  1. WHO. World health statistics 2022 (Monitoring health of the SDGs) [Internet]. Geneva: OMS; 2022 [Cited 24/10/2022]. Available from: Available from: http://apps.who.int/bookorders 1.

  2. Deuschl G, Beghi E, Fazekas F, Varga T, Christoforidi KA, Sipido E, et al. The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017. Lancet Public Health. 2020 oct 1;5(10):e551-67.

  3. Feigin VL, Vos T, Nichols E, Owolabi MO, Carroll WM, Dichgans M, et al. The global burden of neurological disorders: translating evidence into policy. Lancet Neurol. 2020 Mar;19(3):255-65.

  4. Vittori DC, Chamorro ME, Hernández Y, Maltaneri RE, Nesse AB. Erythropoietin and derivatives: Potential beneficial effects on the brain. J Neurochem [Internet]. 2021 Sep [Cited 24/10/2022];158(5):1032-57. Available from: Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/jnc.15475 4.

  5. Rey F, Balsari A, Giallongo T, Ottolenghi S, di Giulio AM, Samaja M, et al5. . Erythropoietin as a Neuroprotective Molecule: An Overview of Its Therapeutic Potential in Neurodegenerative Diseases. SAGE Journals. [Internet]. 2019 Ago [Cited 24/10/2022];11. Available from: Available from: https://journals.sagepub.com/doi/full/10.1177/1759091419871420 5.

  6. Garzón F, Coímbra D, Parcerisas A, Rodríguez Y, García JC, Soriano E, et al. NeuroEPO Preserves Neurons from Glutamate-Induced Excitotoxicity. Journal of Alzheimer's Disease. 2018 Ene;65(4):1469-83.

  7. Fernando G, Yamila R, César GJ, Ramón R. Neuroprotective Effects of neuroEPO Using an In Vitro Model of Stroke. Behavioral Sciences [Internet]. 2018 [Cited 24/10/2022];4. Available from: Available from: https://www.mdpi.com/2076-328X/8/2/26/htm 7.

  8. Maurice T, Mustafa MH, Desrumaux C, Keller E, Naert G, García Barceló LC, et al8. . Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ25-35 non-transgenic mouse model of Alzheimer’s disease. SAGE Journals [Internet]. 2013 Jun [Cited 24/10/2022];27(11):1044-57. Available from: Available from: https://journals.sagepub.com/doi/abs/10.1177/0269881113494939 8.

  9. Cruz YR, Strehaiano M, Rodríguez Obaya T, Rodríguez JCG, Maurice T. An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APP Swe Transgenic Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease. 2017 Ene;55(1):231-48.

  10. Pérez L, Sosa S, Bringas G, López D, Valenzuela C, Peñalver AI, et al10. . NeuroEPO in mild-to-moderate Alzheimer’s disease. Alzheimer’s & Dementia [Internet]. 2020 Dic [Cited 08/08/2022];16(S9):e036167. Available from: Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/alz.036167 10.

  11. Bringas Vega ML, Pedroso Ibáñez I, Razzaq F A, Zhang M, Morales Chacón L, Ren P, et al. The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity. Fronttiers Neuroscience. 2022;16:952.

  12. Santos Morales O, Díaz Machado A, Jiménez Rodríguez D, Pomares Iturralde Y, Festary Casanovas T, González Delgado CA, et al12. . Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: A randomized, parallel, open-label safety study. BMC Neurol [Internet]. 2017 Jul [Cited 08/08/2022];17(1):1-9. Available from: Available from: https://link.springer.com/articles/10.1186/s12883-017-0908-0 12.

  13. Pedroso I, García M, Casabona E, Morales L, Bringas ML, Pérez L, et al13. . Protective Activity of Erythropoyetine in the Cognition of Patients with Parkinson’s Disease. Behavioral Sciences [Internet]. 2018 May [Cited 24/10/2022];8(5):51. Available from: Available from: https://www.mdpi.com/2076-328X/8/5/51/htm 13.

  14. Rodríguez Labrada R, Ortega Sánchez R, Hernández Casaña P, Santos Morales O, Padrón Estupiñán M del C, Batista Núñez M, et al14. . Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study. Movement Disorders [Internet]. 2022 Jul [Cited 24/10/2022];37(7):1516-25. Available from: Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/mds.29045 14.

  15. Fernández Romero T, Clapés Hernández S, Pérez Hernández CL, Barreto López JJ, Fernández Peña G, Fernández Romero T, et al15. . Efecto hipoglicemiante de la NeuroEPO en ratas con y sin diabetes mellitus. Rev Haban Cienc Méd [Internet]. 2022 [Cited 24/10/2022];21(1). Available from: Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X2022000100003&lng=es&nrm=iso&tlng=es 15.

  16. Fernández Romero T, Clapes Hernández S, Pérez Hernández CL, Núñez López N, Suárez Román G, Fernández Peña G. Protective effect of NeuroEPO on the reproduction of diabetic rats. Rev Haban Cienc Méd [Internet]. 2022 Sep [Cited 24/10/2022];21(4):e4797. Available from: Available from: http://www.revhabanera.sld.cu/index.php/rhab/article/view/4797 16.

  17. Suárez Borrás K, Fernández G, Rodríguez Cruz Y, Puldón Seguí G. Intranasal administration of NeuroEPO does not affect the structure of respiratory mucosa in Wistar rats. Rev Haban Cienc Méd [Internet]. 2022 [Cited 24/10/2022];21(4). Available from: Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X2022000100003&lng=es&nrm=iso&tlng=es 17.

  18. Couto M, Cates C. Laboratory Guidelines for Animal Care. Methods Mol Biol [Internet]. 2019 [Cited 30/03/2020];1897: 407-30. Available from: Available from: http://link.springer.com/10.1007/978-1-4939-9009-2_25 18.

  19. McCormick Ell J, Connell N. Laboratory Safety, Biosecurity, and Responsible Animal Use. ILAR J [Internet]. 2019 Ago [Cited 30/03/2020];60(1):24-33. Available from: Available from: https://academic.oup.com/ilarjournal/advance-article/doi/10.1093/ilar/ilz012/5550511 19.

  20. Muñoz Cernada A, García Rodríguez JC, Núñez Figueredo Y, Pardo Ruiz Z, García Selman JD, Sosa Testé I, et al20. . Formulaciones nasales de EPORH con bajo contenido de ácido siálico para el tratamiento de enfermedades del sistema nervioso central [Internet]. Suiza: Patentscope.wipo.int 2007 [Cited 24/10/2022]. Available from: Available from: https://patentscope.wipo.int/search/es/detail.jsf?docId=WO2007009404 20.

  21. Humason GL. Animal tissue techniques. En Su: Animal tissue techniques [Internet]. London: W. H. Freeman and Company; 1962 [Cited 24/10/2022]. Available from: Available from: https://www.cabdirect.org/cabdirect/abstract/19622204447 21.

  22. Uraih LC, Maronpot RR. Normal histology of the nasal cavity and application of special techniques. Environ Health Perspect. 1990 Abr;85:187-208.

  23. Kumar V, Abbas AbulK, Aster JonC. eds. Robbins and Cotran Pathologic Basis of Disease. 10 ed [Internet]. Philadelphia: Elsevier Publication; 2018 [Cited 24/10/2022]. Available from: Available from: https://www.elsevier.com/books/robbins-and-cotran-pathologic-basis-of-disease/kumar/978-0-323-53113-9 23.

  24. Suárez K, Fernández G, Puldón G, Rodríguez Y, Pérez CL. Effect of intranasal administration of neuroEPO in the histological structure of the olfactory mucosa of rats Wistar. [Internet]. Philadelphia: Mendeley Data; 2022 [Cited 24/10/2022]. Available from: Available from: https://data.mendeley.com/datasets/gc77wttd9h 24.

  25. Graff CL, Pollack GM. Nasal Drug Administration: Potential for Targeted Central Nervous System Delivery. J Pharm Sci. 2005 Jun;94(6):1187-95.

  26. Keller LA, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res [Internet]. 2022 Abr [Cited 24/10/2022];12(4):735-57. Available from: Available from: https://link.springer.com/article/10.1007/s13346-020-00891-5 26.

  27. Lagarto A, Bueno V, Guerra I, Valdés O, Couret M, López R, et al27. . Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid. Experimental and Toxicologic Pathology. 2011 Sep;63(6):563-7.

  28. Kovalchuk N. Organ-Specific contribution of P450 enzymes to bioactivation and acute respiratory tract toxicity of naphthalene. Dissertation. New York: State University of New York; 2017.

  29. Cüreoǧlu S, Akkuş M, Osma Ü, Yaldiz M, Oktay F, Can B, et al29. . The effect of benzalkonium chloride on rabbit nasal mucosa in vivo: an electron microscopy study. European Archives of Oto-Rhino-Laryngology 2002 259:7 [Internet]. 2002 [Cited 24/10/2022];259(7):362-4. Available from: Available from: https://link.springer.com/article/10.1007/s00405-002-0458-x 29.

  30. Jiang B, Shi Y, Abou MB, Xu L, Liang G, Wei H. Effects of chronic intranasal dantrolene on nasal mucosa morphology in mice. Eur Rev Med Pharmacol Sci. 2022;26(1):198-203.

  31. Xie F, Zhou X, Genter MB, Behr M, Gu J, Ding X. The Tissue-Specific Toxicity of Methimazole in the Mouse Olfactory Mucosa Is Partly Mediated through Target-Tissue Metabolic Activation by CYP2A5. Drug Metabolism and Disposition [Internet]. 2011 Jun [Cited 24/10/2022];39(6):947-51. Available from: Available from: https://dmd.aspetjournals.org/content/39/6/947 31.




2020     |     www.medigraphic.com