Related Experiment Videos
Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy
R Wada1, Y Nishizawa, N Yagihashi
1Department of Pathology, Hirosaki University School of Medicine, Japan.
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.
Materials And 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.
Conclusion:
The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.
Insights
A new glycation inhibitor, OPB-9195 (OPB), improved nerve function and reduced advanced glycation end-products (AGE) in diabetic rats. This suggests OPB may be a promising agent for preventing diabetic neuropathy.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Nonenzymatic glycation of neural proteins forms advanced glycation end-products (AGE), implicated in diabetic neuropathy pathogenesis.
- Development of effective anti-glycation agents is crucial for clinical applications in managing diabetic complications.
Purpose of the Study:
- To investigate the effects of OPB-9195 (OPB), a novel glycation inhibitor, on peripheral nerve structure and function in a rat model of diabetes.
- To assess OPB's impact on advanced glycation end-products (AGE) and oxidative stress markers in diabetic neuropathy.
Main Methods:
- Diabetic Wistar rats (streptozotocin-induced) were treated with OPB (60 mg/kg/day) or vehicle for 24 weeks.
- Peripheral nerve conduction velocity, sciatic nerve AGE expression, (Na+, K+)-ATPase activity, and oxidative DNA damage (8-hydroxy-2'-deoxyguanosine) were evaluated.
Main Results:
- OPB treatment significantly improved tibial motor nerve conduction velocity by 60% in diabetic rats.
- Reduced serum AGE levels and sciatic nerve AGE expression were observed in OPB-treated rats.
- Restoration of sciatic nerve (Na+, K+)-ATPase activity and decreased oxidative stress markers were noted with OPB treatment.
Conclusions:
- OPB demonstrates beneficial effects in reducing AGE accumulation and preventing structural and functional nerve damage in diabetic neuropathy.
- OPB shows potential as a therapeutic agent for the clinical management of diabetic neuropathy.