Protective effect of gliclazide on diabetic peripheral neuropathy through Drp-1 mediated-oxidative stress and apoptosis

• Published in: Neuroscience letters 2012-08, Vol.523 (1), p.45-49
• Main Authors: Wu, Yuan-bo, Shi, Li-li, Wu, Yuan-jie, Xu, Wen-hua, Wang, Li, Ren, Ming-shan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; Caspase-3; Demyelination; Diabetes mellitus; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - pathology; Diabetic Neuropathies - physiopathology; Diabetic peripheral neuropathy; Dynamin-related protein-1; Gliclazide; Gliclazide - administration & dosage; Hypoglycemic Agents - administration & dosage; Male; Malondialdehyde; Nerve conduction; Nerve conduction velocity; Nervous system; Neuroprotective Agents - administration & dosage; Oxidative stress; Oxidative Stress - drug effects; Peripheral neuropathy; protein L; Rats; Rats, Sprague-Dawley; Sciatic nerve; Sciatic Nerve - drug effects; Sciatic Nerve - physiopathology; Streptozocin; Superoxide dismutase; Treatment Outcome
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2012.06.038

► DPN was induced by intra-peritoneal injection of streptozotocin. ► Expressions of Drp-1, Bax, caspase-3 and MDA increased in sciatic nerve of DPN rat. ► SOD activity and NCV decreased in sciatic nerve of DPN rat. ► Changes of Drp-1, Bax, Bcl-2, caspase-3, MDA and NCV were blocked by gliclazide. Objective: To investigate the protective effect of gliclazide and the role of dynamin-related protein l (Drp-1)-mediated oxidative stress and apoptosis in diabetic peripheral neuropathy (DPN). Methods: Diabetic rats developed through intra-peritoneal injection of streptozotocin were randomly assigned to treatment group receiving gliclazide or non-treatment group without gliclazide treatment. Rats in control group received intra-peritoneal injection of vehicle and no gliclazide treatment. Eight weeks later, the nerve conduction velocity (NCV) of sciatic nerve was measured and the morphological alterations, the malondialdehyde (MDA) level and superoxide-dismutase (SOD) activity, the expressions of Drp-1, caspase-3, Bax and Bcl-2 in sciatic nerve were evaluated. Results: When compared to rats in control group, rats in non-treatment group showed significantly decrease of NCV, obvious demyelinative alteration of sciatic nerve, increased expressions of Drp-1, caspase-3, Bax, Bcl-2 and MDA, and decreased SOD activity. Compared to rats in non-treatment group, rats in treatment group showed significantly increase of NCV, less demyelination of sciatic nerve, decreased expressions of Drp-1, caspase-3, Bax and MDA, and increased activity of SOD. The expression of Bcl-2 was not significantly different between treatment and non-treatment groups. Conclusion: Gliclazide showed protective effect on DPN through modulating Drp-1-mediated oxidative stress and apoptosis.