Short-term intra-nasal erythropoietin administration with low sialic acid content is without toxicity or erythropoietic effects
| Autor: | Jose A. Sanchez, Yamile Vega, Isbel Guerra, Raisell López, Irene Beausoleil, Pedro Barzaga, Micaela Couret, Alicia Lagarto, Tatiana Gabilondo, Odalys Valdes, Viviana Bueno |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pharmacology Neuroprotection Drug Administration Schedule Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Developmental Neuroscience Toxicity Tests Acute Medicine Animals Erythropoiesis Dosing Rats Wistar Erythropoietin Administration Intranasal biology business.industry Immunogenicity N-Acetylneuraminic Acid Sialic acid Rats Neurology chemistry Toxicity biology.protein Nasal administration Female Antibody business medicine.drug |
| Zdroj: | Current neurovascular research. 9(4) |
| ISSN: | 1875-5739 |
| Popis: | The objective of this investigation was to assess the toxicological potential of nasal formulation of erythropoietin with low sialic acid content (Neuro EPO) after 28 days of intra-nasal dosing in rats besides to evaluate the immunogenicity and erythropoietic effect of the test substance. Healthy Wistar rats of both sexes were used for 28 days subacute toxicity and immunogenicity assays. Doses evaluated were 3450, 4830 and 6900 UI/kg/day. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, antibodies determination, selected tissue weights and histopathological examination. Reversibility of toxic effects was evaluated at high dose 14 days after treatment period. Female B6D2F1 mice were used for evaluated erythropoietic effect of the nasal formulation. Hematological endpoints were examined every week during 28 days of intra-nasal dosing of 6900 UI/kg/day. Variations of hematological patterns were not observed after 28 days of intranasal dosing. A slight increase in glucose level of treated animals within the normal range was observed. This effect was not dose related and was reversible. Antibody formation was not observed in any of the test doses. Histopathological examination of organs and tissues did not reveal treatment induced changes. The administration of Neuro EPO in normocythaemic mice did not produce erythropoietic effect. These results suggest that Neuro EPO could be used as a neuroprotective agent, without significant systemic haematological side effects. |
| Databáze: | OpenAIRE |
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