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 pathoge nesis of diabetic neuropathy. We need a development of effective ant-glycat ion agents for future clinical use. Materials and methods We examined the effects of OPB-9195 (OPB), a new inhi bitor of glycation, on the peripheral nerve structure and function in diabe tic rats. Eight-week-old Wister rats were made diabetic by streptozotocin ( 40 mg kg(-1), i.v.) and OPE (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, OPE treatment did not affect the re duced body weight, elevated levels of blood glucose and glycated haemoglobi n in diabetic rats. At the end of the experiment, delayed tibial motor nerv e conduction velocity was significantly improved (by 60%) in treated diabet ic rats, with reduction of serum AGE levels. Expression of immunoreactive A GE in the sciatic nerve was reduced in treated diabetic rats compared with those in untreated rats. Sciatic nerve (Na+,K+)-ATPase activity was also re stored in treated diabetic rats. On the cross-sectioned sciatic nerves, pos itive cells with oxidative stress-related DNA damage, as expressed by 8-hyd roxy-2'-deoxyguanosine, were less in the peripheral nerve of treated diabet ic rats compared with those of untreated rats. Conclusion The current study suggested that OPE is beneficial for the reduc tion of serum AGE and the prevention of diabetic neuropathy.