title: Short-term intra-nasal erythropoietin administration with low sialic acid content is without toxicity or erythropoietic effects.
abstract: 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.
authors.affiliation: Drug Research and Development Center. CIDEM. 17 No. 6208 e/ 62 y 64, Playa, código postal 11300, Ciudad Habana, Cuba. alicialp@infomed.sld.cu
authors.forename: Alicia
authors.initials: A
authors.lastname: Lagarto
authors.forename: Viviana
authors.initials: V
authors.lastname: Bueno
authors.forename: Jose A
authors.initials: JA
authors.lastname: Sanchez
authors.forename: Micaela
authors.initials: M
authors.lastname: Couret
authors.forename: Odalys
authors.initials: O
authors.lastname: Valdes
authors.forename: Pedro
authors.initials: P
authors.lastname: Barzaga
authors.forename: Raisell
authors.initials: R
authors.lastname: Lopez
authors.forename: Isbel
authors.initials: I
authors.lastname: Guerra
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gabilondo
authors.forename: Yamile
authors.initials: Y
authors.lastname: Vega
authors.forename: Irene
authors.initials: I
authors.lastname: Beausoleil
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004334:Drug Administration Schedule; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D008297:Male; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D004921:Erythropoietin; D019158:N-Acetylneuraminic Acid