title: The effects of gliclazide, methylcobalamin, and gliclazide+methylcobalamin combination therapy on diabetic peripheral neuropathy in rats.
abstract: OBJECTIVE
  This study investigated the efficacies of gliclazide (GLZ), methylcobalamin (MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related changes in peripheral nerve function, the polyol pathway, and oxidative stress in the sciatic nerve of streptozotocin-induced diabetic rats.
  
  
  METHODS
  The rat model of streptozotocin-induced diabetes was orally given GLZ (25mg/kg/day), MCA (175μg/kg/day), and GLZ+MCA (25mg/kg/day+175μg/kg/day) combination therapy for 8weeks, in order to observe its effects on the motor nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme activities and peroxidation products in the sciatic never tissue.
  
  
  RESULTS
  Most of the indicators of DPN, such as delayed MNCV, altered/damaged nerve structure, inhibited Na(+),K(+)-ATPase activity, enhanced AR activity and AR mRNA expression, increased polyol contents, altered Cu,Zn-superoxide dismutase, catalase, and glutathione-peroxidase activities, and elevated malondialdehyde level in the sciatic nerves of the diabetic rats, were significantly ameliorated by treatment with either GLZ or MCA. Moreover, the combination of GLZ and MCA was found to enhance the curative effect on DPN in parts of above-mentioned parameters as compared to monotherapy.
  
  
  CONCLUSIONS
  Monotherapy with GLZ or MCA, and especially the combined application of GLZ and MCA, could be efficient therapeutic strategies for combating experimental DPN in diabetic rats.
authors: First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: yaohp2005@126.com.
authors: Hongping
authors: H
authors: Yao
authors: Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, China.
authors: Juanyi
authors: J
authors: Feng
authors: First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Qiaowei
authors: Q
authors: Zheng
authors: First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Youxia
authors: Y
authors: Wei
authors: College of Life Science, Northwest University, Xi'an 710069, China.
authors: Shixiang
authors: S
authors: Wang
authors: First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, China.
authors: Weiyi
authors: W
authors: Feng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005907:Gliclazide / Q000008:administration & dosage*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000473:pathology; D013311:Streptozocin; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001786:Blood Glucose; D013311:Streptozocin; C019476:mecobalamin; D005907:Gliclazide; D014805:Vitamin B 12
keywords: Diabetic peripheral neuropathy; Gliclazide; Methylcobalamin