Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid

The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPO b), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without ris...

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Bibliographic Details
Published in:Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2011-09, Vol.63 (6), p.563-567
Main Authors: Lagarto, Alicia, Bueno, Viviana, Guerra, Isbel, Valdés, Odalys, Couret, Micaela, López, Raisel, Vega, Yamile
Format: Article
Language:English
Subjects:
acute effects
Acute toxicity
Administration, Intranasal
adverse effects
Animals
Biological and medical sciences
brain
Dose-Response Relationship, Drug
Drug-Related Side Effects and Adverse Reactions - blood
edema
Erythropoietin
Erythropoietin - administration & dosage
Erythropoietin - chemistry
Erythropoietin - toxicity
Female
food consumption
histopathology
humans
hypoxia
immune response
Investigative techniques, diagnostic techniques (general aspects)
lymphocytes
Male
males
Medical sciences
N-Acetylneuraminic Acid - analysis
Nasal administration
Nasal irritation
nasal mucosa
Nasal Mucosa - drug effects
Nasal Mucosa - pathology
Neuroprotective Agents - administration & dosage
Neuroprotective Agents - chemistry
Neuroprotective Agents - toxicity
neuroprotective effect
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Rats
Rats, Wistar
risk
sialic acids
Subacute toxicity
tissue weight
toxicity testing
Toxicity Tests, Acute
Toxicity Tests, Subacute
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Summary:The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPO b), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without risk of thrombotic events. The objective of this investigation was to assess the toxicological potential of a nasal formulation with rhEPO b in acute, subacute and nasal irritation assays in rats. Healthy Wistar rats (Cenp:Wistar) were used for the assays. In an irritation test, animals received 15 μl of rhEPO b into the right nostril. Rats were sacrificed after 24 h and slides of the nasal mucosa tissues were examined. Control and treated groups showed signs of a minimal irritation consisting of week edema and vascular congestion in all animals. In the acute toxicity test, the dose of 47,143 UI/kg was administered by nasal route. Hematological patterns, body weight, relative organ weight, and organ integrity were not affected by single dosing with rhEPO b. In the subacute toxicity test, Wistar rats of both sexes received 6,600 UI/kg/day for 14 days. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, selected tissue weights, and histopathological examinations. An increase of lymphocytes was observed in males that was considered to reflect an immune response to treatment. Histopathological examination of organs and tissues did not reveal treatment-induced changes. The administration of rhEPO b at daily doses of 6,600 UI/kg during 14 days did not produce hematological side effects. These results suggest that rhEPO b could offer the same neuroprotection as EPO, without hematological side effects.
ISSN:0940-2993
1618-1433
DOI:10.1016/j.etp.2010.04.008