Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC03
Effects of vitamin-E and L-arginine on experimental diabetic neuropathy in rats
I. Bin-Jaliah1, E. F. Khaleel1,2, S. EL-Attar2, L. A. El-Sayed2, M. A. Haidara1,2
1. Department of Physiology, College of Medicine, King Khalid University, Abha, Aseer, Saudi Arabia. 2. Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Diabetic polyneuropathy is a common chronic complication of diabetes. Oxidative stress is increased in both human and experimental diabetes and has been related to the development of diabetic neuropathy. Vascular factors also have been implicated in the pathogenesis of experimental diabetic peripheral neuropathy (EDPN). The aim of this study was to evaluate the possible contribution of the two pathways, vascular or metabolic, to the development of such neural complication. Ninety adult male Wistar rats (200-250 g) were assigned into 9 groups (n = 10 for each). One group served as a control (vehicle solution, 40 mg.kg-1, I.P.), and 8 experimental groups included streptozotocin-induced (40 mg.kg-1, I.P.) diabetic rats. One diabetic group did not receive any further treatment. Four diabetic groups were treated with a single treatment of the following: insulin (1 IU, S.C., daily), vitamin-E (300 mg.kg-1, I.M., 3 times a week), vitamin-E (600 mg.kg-1, I.M., 3 times a week), L-arginine (50 mg.kg-1, intragastric, daily). Three diabetic groups were treated with 2 treatments (insulin plus one of the 3 other treatments mentioned above). All experimental treatment regimes continued for 4 weeks, after which, under ether (10% for induction, and 5% for maintenance) anaesthesia, nerve conduction velocity (NCV) and amplitude of muscle contraction (AMC) studies were performed, and retro-orbital fasting blood samples were taken for measuring of serum glucose levels. The rats were then humanely killed, under terminal anaesthesia by cervical dislocation, and sciatic nerves were dissected for measuring of malondialdehyde (MDA), glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS). Data are expressed as mean±S.D. and Significance (P<0.05) tested with ANOVA. Diabetic rats had significantly higher serum glucose levels (382.5%), increased oxidative stress (MDA; 261.6%), lower eNOS (74.8%), delayed NCV (63.6%), and lower AMC (36.4%) as compared with the control group. Solitary insulin treatment (but not vitamin-E or L-arginine) corrected serum glucose to control values. However, treating diabetic rats with vitamin-E significantly reduced oxidative stress (using vitamine-E at the dose of 600 mg.kg-1, MDA was decreased by 50%, with increased GPx activity from 0.91±0.21 to 2.79±0.42 nmol.mg-1), and corrected NCV (reducing the latency by 72.03%) and improved AMC by 228.87%. On the other hand, L-arginine treatment had no effect on the oxidative stress markers, but significantly improved NCV (reducing the latency by 79.72%) and increased AMC (by 256.60%). This study supported the notion that EDPN is a multifactorial complication, caused by hyperglycemia, oxidative stress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in higher 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 EDPN.
Where applicable, experiments conform with Society ethical requirements