REMEDIAL EFFECTS OF VITAMIN E AND L-ARGININE ON PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Abstract

It was shown that hyperglycemia in diabetic patient s is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the de velopment of diabetic peripheral neuropathy. A substantial number of studies have shown that antio xidant treatment are promising therapeutics that ca n prevent or correct reduced motor nerve conduction i n diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and strept ozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum gluc ose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction stud ies of the sciatic nerves of these rats showed decr ease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin -E or L-arginine) corrected serum glucose to contro l values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg -1 and 600 mg kg -1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg -1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion tha t diabetic peripheral neuropathy is a multifactoria l complication, caused by hyperglycemia, oxidative st ress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in h igher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.