Neuroprotective Effect of Combined Therapy of Liraglutide with Vitamin D on Streptozotocin-Induced Diabetic Neuropathy in Rats.

Abstract

Background: Liraglutide is an incretin mimetic agent that approved recently in type-2 diabetes. The use of vitamin D was reported to be associated with an improvement in diabetic neuropathy. The aim of the study: Evaluation of the effect of liraglutide and vitamin D each alone and in combination with each other on diabetic neuropathy induced by streptozotocin in rats. Materials and Methods: Five groups of Wistar rats were used in the experiment. Diabetic neuropathy was induced in groups 2, 3, 4, and 5 using a single intraperitoneal(i.p.) injection of streptozotocin(STZ) in a dose of 60 mg/kg. The third, fourth, and fifth groups were treated for 4 weeks with liraglutide (0.8 mg/kg), vitamin D (12 µg/kg), and combination of the 2 drugs, respectively. Then the behavioral tests were done (hot plate, tail-flick, paw withdrawal pressure, and the rotarod tests). Blood samples were used for assessment of blood glucose, tumor necrosis factor-α (TNF-α) and interleukin-Iβ(IL-Iβ).Malondialdehyde(MDA) and glutathione (GSH)were measured in the sciatic nerve homogenate. Results: Liraglutide caused significant improvement in the behavioral tests of the diabetic rats with a significant reduction in blood glucose, TNF-α, IL-1β, and malondialdehyde. Vitamin D caused mild improvement in the behavioral tests, inflammatory and oxidative stress markers. The combined use of liraglutide with vitamin D caused more improvement in diabetic neuropathy tests, inflammatory and oxidative stress markers. Conclusion: Liraglutide has a moderate neuroprotective, anti-inflammatory, and antioxidant effects in cases of streptozotocin-induced diabetic neuropathy which are enhanced by the addition of vitamin D.