title: Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.
abstract: 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 20 weeks. 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 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, 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 ± 2.7 μm(2), 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Heung Yong
authors.initials: HY
authors.lastname: Jin
authors.forename: Kyung Ae
authors.initials: KA
authors.lastname: Lee
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Song
authors.forename: Wei Jing
authors.initials: WJ
authors.lastname: Liu
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Choi
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Song
authors.forename: Hong Sun
authors.initials: HS
authors.lastname: Baek
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004553:Electric Conductivity / Q000009:adverse effects; D004817:Epidermis / Q000294:innervation; D005260:Female; D005753:Gastric Mucosa / Q000294:innervation; D006025:Glycosaminoglycans / Q000494:pharmacology* / Q000627:therapeutic use; D007672:Kidney Cortex / Q000294:innervation; D009186:Myelin Sheath / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D017288:Pain Threshold / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000517:prevention & control*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000098:blood supply; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D006025:Glycosaminoglycans; C007858:glucuronyl glucosamine glycan sulfate; D013482:Superoxide Dismutase