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.
Keywords: Erythropoietic effect, general toxicity, immunogenicity, nasal administration, neuro EPO, subacute toxicity, erythropoietin, thrombotic vascular effects, Mongolian gerbils, blood-modulating hormone
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Published on: 10 October, 2012
Page: [233 - 238]