[Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes].
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.
Cátedra de Farmacología, Escuela José María Vargas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela. yaira57@yahoo.com
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Mathison Natera
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Finol
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Quero
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González
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González
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000473:pathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D004353:Drug Evaluation, Preclinical; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016326:Extracellular Matrix Proteins; D010426:Pentosan Sulfuric Polyester