Neuropharmacology and AnalgesiaSulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats

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 10 mg/kg), diabetic group, and diabetic + Sulodexide (sulodexide 10 mg/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 μm2, 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.