Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats

Abstract

Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10- week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.

Enriched-asafoetida diet attenuates hyperglycemia, oxidative stress and endothelial dysfunction in type 2 diabetic rats

“…Chronic hyperglycemia causes an increase in the glycation of Hb (Nishikawa et al, 2000;Giugliano et al, 2008;Pari and Sankaranarayanan, 2009). HbA1c is considered a more accurate and reliable measure for the management of patients with diabetes than FBS (Taylor et al, 1988;Kristová et al, 2008). Also, it has been considered as a predictor of diabetic complications such as nephropathy, retinopathy, nephropathy and neuropathy (Howlett and Ashwell, 2008).…”

“…Vascular relaxation occurs through two pathways: 1) endothelial-dependent pathway through synthesis of nitric oxide and 2) endothelial-independent pathway (Taylor et al, 1988;Mitchell et al, 2008). Diabetes-induced hyperglycemia disrupts blood vessels through various mechanisms, such as increased oxidative stress, increased secretion of inflammatory cytokines, altered gene expression and vascular endothelial cell signaling (Kristová et al, 2008). It has been documented that antioxidant therapy improves vascular dysfunction in patients with diabetes (Sotnikova et al, 2013).…”

Vasoprotective Effect of Sulodexide in Diabetic Retinopathy

“…In the context of diabetic nephropathy, it's essential to recognize that glycosaminoglycans play a dual role as crucial components of both the endothelial glycocalyx and the glomerular basement membrane [46]. The versatile benefits of sulodexide in individuals with renal complications of diabetes extend to inhibiting inflammatory reactions and mitigating oxidative stress [47,48].…”

Sulodexide Inhibits Arterial Contraction via the Endothelium-Dependent Nitric Oxide Pathway

“…Numerous investigations have been conducted to examine the utilization of SDX in the context of peripheral arteriopathy, metabolic disorders linked to arteriosclerosis, vascular complications arising from diabetes, and venous pathologies [3,4,[17][18][19][20][21][22][23][24][25]. Cospite et al measured the capillary filtration coefficient to assess microcirculation changes and measured a lower coefficient in the SDX-administered group, indicating a lower capillary permeability [26].…”