The Heparanase Inhibitor (Sulodexide) Decreases Urine Glycosaminoglycan Excretion and Mitigates Functional and Histological Renal Damages in Diabetic Rats

Abstract

Background/objectives: 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 effects 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) significantly 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 significantly 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.

Sulodexide for Diabetic-Induced Disabilities: A Systematic Review and Meta-Analysis

“…Sulodexide is a glycosaminoglycan that comprises two fractions: fast-moving heparin fraction (80%) that has affinity for antithrombin III, plus a dermatan sulfate fraction (20%) that has affinity for heparin cofactor II [18]. Experimental investigations showed a favorable effect of sulodexide in diabetic rats, not only reducing proteinuria [19,20] but also protecting the endothelial morphology and function [21][22][23]. This could be associated with a protective and regenerating action on the glycocalyx in experimental studies [24][25][26][27] and in humans [28].…”