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 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.


CONCLUSIONS
Gliclazide showed protective effect on DPN through modulating Drp-1-mediated oxidative stress and apoptosis.
Department of Neurology, Affiliated Anhui Provincial Hospital, Anhui Medical University, PR China.
Yuan-bo
YB
Wu
Li-li
LL
Shi
Yuan-jie
YJ
Wu
Wen-hua
WH
Xu
Li
L
Wang
Ming-shan
MS
Ren
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D005907:Gliclazide / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D005907:Gliclazide