Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway.
Qing-Rong LiZhuo WangWei ZhouShou-Rui FanRun MaLi XueLu YangYa-Shan LiHong-Li TanQing-Hua ShaoHong-Ying YangPublished in: Neural regeneration research (2016)
Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.
Keyphrases
- peripheral nerve
- oxidative stress
- type diabetes
- diabetic rats
- blood glucose
- induced apoptosis
- wound healing
- randomized controlled trial
- high fat diet
- signaling pathway
- dna damage
- adipose tissue
- hydrogen peroxide
- poor prognosis
- glycemic control
- physical activity
- metabolic syndrome
- high throughput
- spinal cord
- single cell
- neuropathic pain
- nitric oxide
- cell proliferation
- binding protein
- insulin resistance
- chemotherapy induced
- heat stress
- heat shock protein