Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats

• Published in: European journal of pharmacology Vol. 674; no. 2-3; pp. 217 - 226
• Main Authors: Jin, Heung Yong, Lee, Kyung Ae, Song, Sun Kyung, Liu, Wei Jing, Choi, Ji Hae, Song, Chang Ho, Baek, Hong Sun, Park, Tae Sun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2012
• Subjects: Animal models; Animals; Axons; Axons - drug effects; blood; blood flow; Blood Glucose - metabolism; Body Weight - drug effects; Cell Count; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Electric Conductivity - adverse effects; Epidermis - innervation; Female; Fibers; Foot; Gastric Mucosa - innervation; Glycosaminoglycans - pharmacology; Glycosaminoglycans - therapeutic use; Intraepidermal nerve fibers; Kidney Cortex - innervation; Microvasculature; morphometry; Myelin Sheath - drug effects; nerve fibers; Nerve Fibers - drug effects; Nerve Fibers - pathology; nerve tissue; Neuropathy; Oral administration; Pain Threshold - drug effects; Perception; Peripheral nerves; Peripheral Nerves - drug effects; Peripheral Nerves - metabolism; Peripheral Nerves - pathology; Peripheral Nerves - physiopathology; peripheral nervous system diseases; Peripheral Nervous System Diseases - complications; Peripheral Nervous System Diseases - prevention & control; Peripheral neuropathy; pharmacology; protective effect; Proteinuria; Proteinuria - drug therapy; Rats; Rats, Sprague-Dawley; Regional Blood Flow - drug effects; Sciatic nerve; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Sciatic Nerve - pathology; Sciatic Nerve - physiopathology; Skin; Skin - blood supply; Streptozocin; streptozotocin; Sulodexide; Superoxide dismutase; Superoxide Dismutase - metabolism; Diabetes; Neuropathy; Sulodexide; Intraepidermal nerve fibers
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.05.059

We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague–Dawley (SD) rats were divided into the following 4 groups (n=7–9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000Hz (633.3±24.15 vs 741.2±23.5μA, P<0.05) and skin blood flow was improved (10.90±0.67 vs 8.85±0.49TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6±2.2 vs 49.8±2.7μm2, P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27±0.24 vs 5.40±0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy. ► Sulodexide prevented diverse peripheral nerve degeneration. ► Sulodexide alleviated the increased thresholds in response of sine-wave stimuli. ► The neuroprotection from sulodexide attributed to improved oxidative stresses. ► Sulodexide is a promising novel therapeutic agent for diabetic peripheral neuropathy.