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

Objective: To investigate the protective effect of gliclazide and the role of dynamin-related protein I (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 BcI-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. BcI-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 BcI-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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.