Open AccessEpalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway
Author(s) -
Qingrong Li,
Zhuo Wang,
Wei Zhou,
Shou-rui Fan,
Ruicheng Ma,
Li Xue,
Lu Yang,
Yashan Li,
Hong-Li Tan,
Qiyue Shao,
Hyejin Yang
Publication year - 2016
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.177745
Subject(s) - aldose reductase , aldose reductase inhibitor , peripheral neuropathy , polyol pathway , oxidative stress , streptozotocin , endocrinology , medicine , superoxide dismutase , diabetic neuropathy , diabetes mellitus , sciatic nerve , intraperitoneal injection , antioxidant , pharmacology , chemistry , biochemistry
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.