RESUMO
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.
Assuntos
Eritropoese/fisiologia , Eritropoetina/administração & dosagem , Ácido N-Acetilneuramínico/administração & dosagem , Testes de Toxicidade Aguda , Administração Intranasal , Animais , Esquema de Medicação , Eritropoese/efeitos dos fármacos , Eritropoetina/toxicidade , Feminino , Masculino , Camundongos , Ácido N-Acetilneuramínico/toxicidade , Ratos , Ratos Wistar , Testes de Toxicidade Aguda/métodosRESUMO
El objetivo de esta investigación fue evaluar los niveles del ácido siálico (S) y enzimas hepáticas en individuos que consumieron agua con arsénico (As) relacionándolos con la presencia ("I con H") o no de hepatomegalia ("I sin H"). Se incluyeron 200 individuos, 85 correspondieron al Grupo Control (GC), 32 "I con H" y 83 "I sin H" quienes habían consumido agua con niveles mayores a 0,01 mg/L. Se les tomó una muestra de sangre venosa y se les realizó el dosaje del S y de las enzimas alaninaninotransferasa (ALT), aspartatoaminotransferasa (AST), fosfatasa alcalina (FAL), gamma glutamil transferasa (GGT), bilirrubina directa (BD) y total (BT), lactato deshidrogenasa (LDH) y 5' nucleotidasa (5'Nu). En los individuos que consumieron agua contaminada se encontró un aumento de los niveles del S. En el grupo "I con H", la FAL, la GGT y la LDH se encontraron aumentadas. En el grupo "I sin H", la GGT y la LDH tuvieron niveles elevados. En los individuos expuestos al As, no se encontraron alteraciones en los otros parámetros bioquímicos estudiados y la prevalencia de hepatomegalia no fue significativa. Los cambios bioquímicos encontrados fueron compatibles con la presencia de un patrón colestásico. Estos datos muestran que la concentración del S sérico podría servir como un indicador de exposición al arsénico que podría ser utilizado en forma conjunta con otros marcadores.
The aim of this study was to investígate the relationship between the levels of serum sialic acid (S) and hepatic enzymes in individuáis who drink As contaminated water. Two hundred individuáis were selected: 85 were the control group, 32 presented hepatomegaly (I with H) and 83 did not present hepatomegaly (I without H) who had consumed drinking water containing As levels higher than O.Ol mg/L. Blood samples were collected for the determination of S and hepatic enzymes in serum: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FAL), gamma glutamil transpeptidase (GGT), direct (BD) and total bilirrubin (BT), lactate deshydrogenase (LDH) and 5'nucleotldase (5'Nu). The populatlon exposed to As in drinking water presented high levels of S, FAL, GGT, LDH and GGT, LDH were increased in I with H and I without H respectively. No significant changes were observed in the other parameters studied. Prevalence of hepatomegaly was not significantly higher and the hepatic biochemical changes were related with the presence of cholestasis in As-exposed people. These data show that people with high As level intake would have an increased sialoprotein replacement which could be an marker with other one of the alterations caused by arsenic.