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Vol. 30. Issue. 6.November 2010
Pages 599-714
Vol. 30. Issue. 6.November 2010
Pages 599-714
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Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with Type 1 diabetes
El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1
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, Yaira Mathison Naterab, Y.. Mathison Naterac, Hector José Finold, H.J.. Finole, Zaida Querob, Z.. Queroc, Roschman Gonzálezd, R.. Gonzáleze, Julio Gonzálezf, J.. Gonzálezg
b Cátedra de Farmacología de la Escuela José María Vargas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela,
c Cátedra de Farmacología, Escuela José María Vargas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela,
d Centro de Microscopía Electrónica "Dr. Mitsuo Ogura", Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela,
e Centro de Microscopía Electrónica Dr. Mitsuo Ogura, Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela,
f Centro de Investigaciones Médicas y Biotecnológicas, Universidad de Carabobo., Valencia, Venezuela,
g Centro de Investigaciones Médicas y Biotecnológicas, Universidad de Carabobo, Valencia, Venezuela,
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Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

Keywords:
Diabetes
Keywords:
kidney damage
Keywords:
Microalbuminuria
Keywords:
Glycosaminoglycans

Se ha comunicado una disminución de los valores de glicosaminoglicanos (GAG) en el riñón y otros órganos en modelos experimentales de diabetes y en humanos. La administración a largo plazo de heparina y otros GAG previene las alteraciones morfológicas y funcionales del riñón en ratas diabéticas. Evaluamos el efecto del pentosán polisulfato de sodio (PPSNa), un mucopolisacárido semisintético similar a los GAG y de baja actividad anticoagulante, sobre la función renal y los cambios estructurales en ratas diabéticas. La diabetes fue inducida a ratas Sprague-Dawley mediante la administración i.v. de estreptozotocina (STZ). Los animales fueron distribuidos al azar en tres grupos (C = control, STZ y STZ + PPSNa = pretratados con 15 mg/kg/día de PPSNa s.c.). Después de 3 meses se tomaron muestras de sangre y de orina de 24 horas; los animales fueron sacrificados y los riñones extraídos mediante microdisección para el análisis morfométrico. Los animales del grupo STZ presentaron un incremento importante de la excreción de albúmina en orina (C = 0,26 ± 0,03 frente a STZ = 7,75 ± 1,8 mg/24 h), que fue parcialmente revertido por el pretratamiento con PPSNa (3,7 ± 0,7 mg/24 h), sin afectar al control metabólico, HbA1c (C = 3,6 ± 1,7; STZ = 8,82 ± 0,47; STZ + PPSNa = 8,63 ± 0,54). En las micrografías electrónicas se observan las lesiones renales habituales descritas en la diabetes experimental (grupo STZ). La administración de PPSNa previene el engrosamiento de la membrana basal tubular y la pérdida de la citoarquitectura inducida por la diabetes. Nuestros resultados demuestran que la administración de PPSNa previene parcialmente el daño renal en este modelo experimental y sugieren un potencial uso terapéutico de este compuesto.

Palabras clave:
Diabetes
Palabras clave:
Daño renal
Palabras clave:
Microalbuminuria
Palabras clave:
Glicosaminoglicanos
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