Gliclazide inhibits diabetic neuropathy irrespective of blood glucose levels in streptozotocin-induced diabetic rats.
N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-alpha (TNF-alpha) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-alpha inhibitor. Rats were fed with powder chow mixed with gliclazide or glibenclamide as a control ad libitum. Blood glucose levels and body weight were remarkably higher and lower in diabetic than in nondiabetic rats, respectively, while gliclazide and glibenclamide had no effect on these in both diabetic and nondiabetic rats throughout a 24-week experiment. Serum lipoperoxide levels and lipopolysaccharide (LPS)-induced serum TNF-alpha activities were significantly increased in diabetic rats, whereas these were significantly inhibited in gliclazide-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve significantly slowed in diabetic rats compared with nondiabetic rats. On the other hand, the slowed MNCV was significantly inhibited in gliclazide-treated diabetic rats after 16 experimental weeks. Morphometric analysis showed that gliclazide prevented decreased myelinated fiber area (P < .05), increased fiber density (P < .001), and decreased axon/myelin ratio (P < .05) in diabetic rats. Glibenclamide treatment did not affect serum lipoperoxide, TNF-alpha, MNCV, or nerve morphology in this experiment. These results indicate that gliclazide has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats, irrespective of blood glucose levels.
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
X
X
Qiang
J
J
Satoh
M
M
Sagara
M
M
Fukuzawa
T
T
Masuda
S
S
Miyaguchi
K
K
Takahashi
T
T
Toyota
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005907:Gliclazide / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013979:Tibial Nerve / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005907:Gliclazide