El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1 / Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes

Se ha reportado 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 mucopolis acárido 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 PPSN a (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 típicas 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 (AU)

Decreased levels of glycosaminoglycans (GAG) have been observed in kidney and other organs, in human and animal models of diabetes. Long term administration of heparins and other glycosaminoglycans have demonstrated a beneficial effect on morphological and functional renal abnormalitiesin diabetic rats. We assessed the effect of sodium pentosen polysulfate (SPP), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on renal involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague Dawley rats by i.v. administration of streptozotocin (STZ).Animals were randomly allocated in three groups: C = control, STZ and STZ + SPP = pretreated with SPP (15 mg/kg, s.c.).After three months of follow-up, blood and 24 h-urine samples were obtained and then the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinaryalbumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs. STZ = 7.75 ± 1.8 mg/24 h) andSPP treatment partially prevented the albumin rise (3.7 ± 0.7mg/24 h), without affecting the metabolic control HbA1c(C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + SPP = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). SPP administration prevent the tubular basement membrane thickening and the lost of cytoarchitecture induced by experimental diabetes. Our data demonstrated that long-term administration of SPP have a favorable effect on morphological and functional abnormalities in kidney of diabetic rats and suggests a potential therapeutic use for this compound (AU)

[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.

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 (15 mg/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.