Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy.
BACKGROUND
Nonenzymatic glycation of neural proteins and their end-products (advanced glycation end-products, AGE) have been implicated in the pathogenesis of diabetic neuropathy. We need a development of effective ant-glycation agents for future clinical use.


METHODS
We examined the effects of OPB-9195 (OPB), a new inhibitor of glycation, on the peripheral nerve structure and function in diabetic rats. Eight-week-old Wistar rats were made diabetic by streptozotocin (40 mg kg(-1), i.v.) and OPB (60 mg kg(-1) day(-1)) was given by gavage for 24 weeks. Age- and sex-matched normal Wistar rats were used for comparison.


RESULTS
During the experimental period, OPB treatment did not affect the reduced body weight, elevated levels of blood glucose and glycated haemoglobin in diabetic rats. At the end of the experiment, delayed tibial motor nerve conduction velocity was significantly improved (by 60%) in treated diabetic rats, with reduction of serum AGE levels. Expression of immunoreactive AGE in the sciatic nerve was reduced in treated diabetic rats compared with those in untreated rats. Sciatic nerve (Na+, K+)-ATPase activity was also restored in treated diabetic rats. On the cross-sectioned sciatic nerves, positive cells with oxidative stress-related DNA damage, as expressed by 8-hydroxy-2'-deoxyguanosine, were less in the peripheral nerve of treated diabetic rats compared with those of untreated rats.


CONCLUSIONS
The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.
Wada
R
R
Department of Pathology, Hirosaki University School of Medicine, Japan.
Nishizawa
Y
Y
Yagihashi
N
N
Takeuchi
M
M
Ishikawa
Y
Y
Yasumura
K
K
Nakano
M
M
Yagihashi
S
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D003929:Diabetic Neuropathies / Q000097:blood / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013830:Thiadiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; C105739:OPB 9195; D013830:Thiadiazoles; D053778:Thiazolidines