Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan

Radhakrishnamurthy, B.; Sharma, C.B.; Bhandaru, R.Rao; Berenson, Gerald S.; Stanzani, Luciano; Mastacchi, R.

doi:10.1016/0021-9150(86)90006-7

Cited by 24 publications

(13 citation statements)

References 20 publications

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“…It has been reported that contrast media can result in hemodynamic alteration of renal blood flow such as vasoconstriction, and led to subsequent renal I/R injury. In this study, we found that Ioversol infusion induced decrease in plasma ATIII activity while Sulodexide pretreatment significantly restored ATIII activity, which was consistent with Sulodexide's biological properties of promoting activation of ATIII [32,33]. Our previous studies demonstrated that low ATIII activity increased the susceptibility to AKI after cardiac surgery in patients and endogenous ATIII insufficiency and exacerbated renal I/R injury in animal model [34].…”

Section: Discussionsupporting

confidence: 48%

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H₂O₂-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

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Section: Discussionsupporting

confidence: 48%

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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“…Increased blood cholesterol can bind to receptors on the mesangial cells, leading to cellular proliferation, matrix accumulation, and the production of cytokines, which can boost the progression of pathological changes in renal sclerosis [32] . In animals fed a diet containing cholesterin, sulodexide was able to reduce the level of plasma cholesterin 12] . In the present study, the serum cholesterin levels of the sulodexide-treated group were significantly lower than those of the model control group.…”

Section: Discussionmentioning

confidence: 99%

“…Mitigation of injury to renal vascular endothelial cells may delay the progression of CRF pathological lesions [20] . Promoting the repair of the injured endothelium can achieve the effect of stabilizing renal function and delaying the progression of pathological changes that are not related to the control of blood pressure and proteinuria [12] . It has been found in animal models that sulodexide protects vascular endothelial cells from detachment [26] .…”

Section: Discussionmentioning

confidence: 99%

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Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure

Xie

et al. 2012

Acta Pharmacol Sin

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Aim: Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats. Methods: Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot. Results: Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group. Conclusion: Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

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“…In a cholesterol-fed rabbit model, sulodexide significantly reduced plasma cholesterol levels and cholesterol accumulation in the rabbit abdominal aorta compared with controls 47. The disappearance of radiolabeled low-density lipoprotein (LDL) was enhanced after the addition of sulodexide in liver perfusates of healthy, lipidemic, or hypertriglyceridemic rats.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Use of sulodexide in patients with peripheral vascular disease

J¹,

Coronel²,

Aza³

et al. 2010

JBM

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Sulodexide is a highly purified glycosaminoglycan containing a combination of heparan sulfate with affinity for antithrombin III and dermatan sulfate with affinity for heparin cofactor II. This antithrombotic and antithrombin activity is of great pharmacologic interest and makes sulodexide a suitable drug for the prophylaxis and treatment of arterial and venous peripheral diseases. In arterial pathology, changes in the Winsor Index, improvement in peripheral blood flow, and reduction in pain-free walking distance confirm that treatment with oral sulodexide is effective. Lipid components linked to the genesis of peripheral vascular processes, including triglycerides, total cholesterol, and low-density lipoprotein fractions, as well as plasma and blood viscosity, are reduced by the administration of sulodexide, whereas the high-density lipoprotein fraction increases. Sulodexide inhibits aggregation and adhesion of platelets at the level of the vascular wall, reduces plasma fibrinogen concentrations, reduces plasminogen activator inhibitor-1, and increases tissue plasminogen activator, as well as systemic fibrinolytic and thrombolytic activity, thereby demonstrating efficacy in the treatment of thromboembolic disease. There is no interaction between sulodexide and other drugs used as long-term treatment for peripheral vascular disease. It is well tolerated, and the adverse reactions described after oral administration are related mainly to transient gastrointestinal intolerance, ie, nausea, dyspepsia, and minor bowel symptoms. Sulodexide may become the treatment of choice when dealing with vascular diseases and their complications, as well as for the prevention of venous thromboembolic disease, being particularly indicated in elderly patients, due to its good tolerability and ease of management.

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Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan

Cited by 24 publications

References 20 publications

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure

Use of sulodexide in patients with peripheral vascular disease

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