THE HEPARANASE INHIBITOR (SULODEXIDE) DECREASES URINE GLYCOSAMINOGLYCAN EXCRETION AND MITIGATES FUNCTIONAL AND HISTOLOGICAL RENAL DAMAGES IN DIABETIC RATS

Recent data suggest a role for heparanase in several
proteinuric conditions. An increased glomerular heparanase expression is associated with
loss of heparan sulfate in the glomerular basement membrane (GBM). The aim of the
present study was to investigate the renal eff ects of heparanase inhibition in a diabetic
experimental model. Methods: Fifteen male Wistar rats (230 ± 20 g) were divided into
three groups: 1) controls, 2) diabetics (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetics
+ heparanase inhibitor (Sulodexide 1/5 mg/kg per day, gavage). The treatment started on
the 21st day, for 21 consecutive days. The rats were kept individually in a metabolic cage
(8 AM-2 PM) and urine samples were collected on the 21st and 42nd day. At study end
blood, urine and tissue samples were collected for biochemical (blood BUN and Cr, urine
GAG and Protein) and histological analyses. Results: The results of this study showed that
the heparanase inhibitor (sulodexide) signifi cantly decreased urine GAG and protein excretion,
urine protein/creatinine ratio and serum BUN and Cr in streptozotocin-induced DN in
the rats. Pathological changes were signifi cantly alleviated in the DN rats having received
the heparanase inhibitor (sulodexide). Conclusion: Our data suggest that the heparanase
inhibitor (sulodexide) is able to protect against functional and histopathological injury in DN