Efecto protector de la NeuroEPO en la reproducción de ratas diabéticas
Resumen
Introducción: la diabetes pre-gestacional constituye un riesgo reproductivo, lo que requiere nuevas estrategias de tratamiento. Teniendo en cuenta que la NeuroEPO, una variante de la eritropoyetina recombinante humana producida en Cuba, tiene efectos neuroprotectores e hipoglicemiantes.
Objetivo: evaluar el efecto protector de la NeuroEPO en la reproducción de ratas diabéticas.
Material y Métodos: se utilizaron cuatro grupos de ratas Wistar hembras adultas, con diabetes inducida por estreptozotocina. Durante la gestación, un grupo recibió el vehículo y el resto diferentes dosis de NeuroEPO (0,5 mg/kg, 0,75 mg/kg y 1 mg/kg), por vía subcutánea, en días alternos, para un total de seis aplicaciones. Se empleó un grupo de ratas no-diabéticas como control. Se evaluó la glicemia y variables reproductivas. Para las comparaciones se empleó el Análisis de Varianza y la Prueba Exacta de Fisher. Las diferencias se consideraron significativas con valores de p menores que 0,05.
Resultados: el grupo con vehículo presentó hiperglicemia mantenida, menor número de implantaciones y embriones, e incremento de las pérdidas gestacionales. En el grupo que recibió 0,5 mg/kg de NeuroEPO, la glicemia disminuyó de forma significativa y los resultados de las variables reproductivas fueron similares al grupo de ratas no-diabéticas. Con las dosis superiores de NeuroEPO se incrementaron las pérdidas gestacionales. No se identificaron malformaciones congénitas en ninguno de los grupos.
Conclusiones: la administración reiterada de 0,5 mg/kg de NeuroEPO tiene efecto beneficioso en la reproducción de ratas diabéticas, que puede estar asociado a la reducción de la hiperglicemia. Otros mecanismos citoprotectores de la NeuroEPO deben ser evaluados en futuros estudios.
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Referencias
Licea ME, Acosta A, Álvarez VA, Aldana D, Arnold Y, Álvarez Y, et al. Diabetes mellitus. Una mirada integral [Online]. La Habana: Editorial Ciencias Médicas; 2021 [Cited 21/01/2022]. Available from: http://www.bvscuba.sld.cu/libro/diabetes-mellitus-una-mirada-integral//
Dirección de Registros Médicos y Estadísticas de Salud. Anuario estadístico de salud 2019 [Online]. La Habana: Ministerio de Salud Pública; 2020 [Cited 21/01/2022]. Available from: http://files.sld.cu/bvscuba/files/2020/05/Anuario-Electrónico-Español-2019-ed-2020.pdf
Yu L, Zeng XL, Cheng ML, Yang GZ, Wang B, Xiao ZW, et al. Quantitative assessment of the effect of pre-gestational diabetes and risk of adverse maternal, perinatal and neonatal outcomes. Oncotarget [Online]. 2017;8(37):61048-56. Available from: http://doi.org/10.18632/oncotarget.17824
Ornoy A, Reece EA, Pavlinkova G, Kappen C, Kermit R. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Research (Part C) [Online]. 2015;105:53-72. Available from: http://doi.org/10.1002/bdrc.21090
Eriksson UJ, Wentzel P. The status of diabetic embryopathyUpsala Journal of Medical Sciences [Online]. 2015;121(2):96-112. Available from: http://doi.org/10.3109/03009734.2016.1165317
Loeken MR. Mechanisms of congenital malformations in pregnancies with pre-existing diabetes. Curr Diab Rep [Online]. 2020;20(10):54. Available from: http://doi.org/10.1007/s11892-020-01338-4
Suresh S, Rajvanshi PK , Noguchi CT. The many facets of erythropoietin physiologic and metabolic response. Front Physiol [Online]. 2020;10:1534. Available from: http://doi.org/10.3389/fphys.2019.01534
Chen ZY, Asavaritikrai P, Prchal JT, Noguchi CT. Endogenous
erythropoietin signaling is required for normal neural progenitor cell
proliferation. J Biol Chem [Online]. 2007;282(35):25875-83. Available from: http://doi.org/10.1074/jbc.M701988200
Ji YQ, Zhang YQ, Li MQ, Du MR, Wei WW, Li DJ. EPO improves the
proliferation and inhibits apoptosis of trophoblast and decidual stromal
cells through activating STAT-5 and inactivating p38 signal in human
early pregnancy. Int J Clin Exp Pathol. 2011;4(8):765-74.
Niu HS, Shan Ch, Niu Sh, Cheng J, Lee K. Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats. Drug Des Dev Ther [Online]. 2016;10:1877-84. Available from: http://doi.org/10.2147/DDDT.S1058677
Kuo Sh, Li Y, Cheng KcH, NiuCh, Cheng J, Niu H. Investigation of the pronounced erythropoietin-induced reduction in hyperglycemia in type 1-like diabetic rats. Endocr J [Online]. 2018;65(2):181-91. Available from: http://doi.org/10.1507/endocrj.EJ17-0353
EL Okela AZ, El Arbagyb AR, Yasseinb YS, Khodirc, Kasemb HE. Effect of erythropoietin treatment on hemoglobin A1c levels in diabetic patients with chronic kidney disease. J Egypt Soc Nephrol Transplant [Online]. 2019;19(3):86-94. Available from: http://doi.org/10.4103/jesnt.jesnt_2_19
Peng B, Kong G, Yang C, Ming Y. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis [Online]. 2020;11(2):2-12. Available from: http://doi.org/10.1038/s41419-020-2276-8
Garzón F, Rodríguez Y, García JC, Rama R. Neuroprotective effects of NeuroEPO using an in vitro model of stroke. Behav Sci (Basel) [Online]. 2018;8(26):1-11. Available from: http://doi.org/10.3390/bs8020026
Garzón F, Coimbra D, Parcerisas A, Rodriguez Y, García JC, Soriano E, et al. NeuroEPO preserves neuronsfromglutamate-inducedexcitotoxicity. J Alzheimers Dis [Online]. 2018;65(4):1469-83. Available from: http://doi.org/10.3233/JAD-180668
Rama R, Garzón F, Rodríguez Cruz Y, Maurice T, García Rodríguez JC. Neuroprotective effect of Neuro-EPO in neurodegenerative diseases: “Aleajactaest”. Neural Regen Res [Online]. 2019;14(9):1519-21. Available from: http://doi.org/10.4103/1673-5374.255968
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: http://doi.org/10.3233/JAD-160500
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 21/01/2022];21(1):e4617. Available from: http://www.revhabanera.sld.cu/index.php/rhab/article/view/4617
Yilmaz O, Lambrecht FY, Gokmen N, Erbayraktar S, Durkan K. Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats. Journal of Radioanalytical and Nuclear Chemistry [Online]. 2007;273(2):311-3. Available from: http://doi.org/10.1007/s10967-007-6859-y
Kaushik K, Vaswani R. Research on animals and current UGC guidelines on animal dissection and experimentation: A critical analysis. Bioethics Update [Online]. 2018;4(2):119-39. Available from: http://doi.org/10.1016/j.bioet.2018.05.001
McCormick Ell J, Connell N. Laboratory safety, biosecurity and responsible animal use. ILAR J [Online]. 2019;60(1):24-33. Available from: http://doi.org/10.1093/ilar/ilz012
Sinzato YK, Kloppel E, Miranda CA, Paula VG, Alves LF, Nascimento LLS, et al. Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies. Laboratory Animals [Online]. 2021;1:1-11. Available from: http://doi.org/10.1177/00236772211001895
Karwasik Kajszczarek K, Chmiel Perzyńska I, Marcin J, Billewicz Kraczkowska A, Pedrycz A, Smoleń A, et al. Impact of experimental diabetes and chronic hypoxia on rat fetal body weight. Ginekologia Polska [Online]. 2018;89(1):20-4. Available from: http://doi.org/10.5603/GP.a2018.0004
Quinna NA, Badwan AA. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats. Drug Design, Development and Therapy [Online]. 2015;9:2515-25. Available from: http://doi.org/10.2147/DDDT.S79885
Fernández T, Suárez G, Clapés S. Protocolo para la citología vaginal directa de ratas de laboratorio. Rev haban cienc méd [Online]. 2021 [Cited 21/01/2022];20(3): e4086. Available from: http://www.revhabanera.sld.cu/index.php/rhab/article/view/4086
Fernández T, Clapés S, Suárez G, Perera A, Rodríguez VM, Purón CA, et al. Embriopatía diabética en ratas y efecto de un suplemento nutricional de vitamina E durante la gestación. Rev haban cienc méd [Online]. 2013 [Cited 21/01/2022];12(2): [Aprox.1p.]. Available from: http://www.revhabanera.sld.cu/index.php/rhab/article/view/56
Fernández Romero T, Clapes S, Pérez CL, Núñez López N, Suárez Román G, Fernández G. Protectiveeffect of NeuroEPO onthereproduction of diabeticrats [Online]. Amsterdam: Mendeley Data; 2022 [Cited 21/01/2022]. Available from: https://www.data.mendeley.com/datasets/dvk9rtwccy/1
Pan Y, Hong X, Li L, Hong Y, Yan Q, Min H, et al. Erythropoietin reduces insulin resistance via regulation of its receptor-mediated signaling pathways in db/db mice skeletal muscle. Int J Biol Sci [Online]. 2017;13(10):1329-40. Available from: http://doi.org/10.7150/ijbs.19752
El Desouki NI, Tabl GA, Abdel Aziz KK, Salim EI, Nazeeh N. Improvement in beta-islets of Langerhans in alloxan-induced diabetic rats by erythropoietin and spirulina. The Journal of Basic and Applied Zoology [Online]. 2015;71:20-31. Available from: http://doi.org/10.1016/j.jobaz.2015.04.003
Chen L, Sun Q, Liu S, Hu H, Lv J, Ji W, et al. Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats. Molecular Medicine Reports [Online]. 2015;12:5391-98. Available from: http://doi.org/10.3892/mmr.2015.4006
Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, et al. Challenges and issues with streptozotocin-induced diabetes- A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chemico Biological Interactions [Online]. 2016;244:49-63. Available from: http://doi.org/10.1016/j.cbi.2015.11.032
Jawerbaum A, White V. Animal models in diabetes and pregnancy. Endocrine Reviews [Online]. 2010;31(5):680-701. Available from: http://doi.org/10.1210/er.2009-0038
Weishaupt JH, Rohde G, Pölking E, Siren AL, Ehrenreich H, Bähr M. Effect of Erythropoietin Axotomy-Induced Apoptosis in Rat Retinal Ganglion Cells. Invest Ophthalmol Vis Sci. 2004;45(5):1514-22.
Ribatti D, Presta M, Vacca A, Ria R, Giuliani R, Dell’Era P, et al. Human Erythropoietin Induces a Pro-Angiogenic Phenotype in Cultured Endothelial Cells and Stimulates Neovascularization In Vivo. Blood. 1999;93(8):2627-36.
Teste IS, Tamos YM, Cruz YR, Cernada AM, Rodríguez JC, Martínez NS, et al. Dose effect evaluation and therapeutic window of the neuro-EPO nasal application for the treatment of the focal ischemia model in the Mongolian gerbil. Scientific World Journal [Online]. 2012 [Cited 21/01/2022];2012:607498. Available from: http://europepmc.org/abstract/MED/22701364
Voss AK, Strasser A. The essentials of developmental apoptosis. F1000Research [Online]. 2020 [Cited 21/01/2022];9:[Aprox. 2 p.]. Available from: http://www.pmc/articles/PMC7047912/
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