Evaluation of Canagliflozin as Neuroprotective Agent in Experimental Diabetic Neuropathy.

Background: Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes. As one of the most common complications, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed type2 diabetes mellitus (T2DM) patients have DPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years.Objectives: to investigate the potential neuro-protective effect of canagliflozin in DPN in diabetic rats and explore the underlying mechanism.Methods: Sprague Dawley rats (n 50) were randomly categorized into five groups; control, diabetic (nicotinamide-streptozotocin), canagliflozin20mg/kg, Canagliflozin 10mg/kg, Pregabalin 10mg/kg. Neuropathy was evaluated by tail flick test, acetone test, grip strength test. Biochemically sciatic nerve malondialdehyde (MDA), super oxide dismutase (SOD), interleukin-6(IL6) levels were measured. Histopathological changes in sciatic nerve were evaluated also matrix metalloproteinase 9 (MMP9) immunohistochemical staining.Results: induction of T2DM by nicotinamide 50mg/kg followed by streptozotocin 52.5mg/kg in rats revealed by a significant increase in blood glucose level. DPN assessed by behavioral tests as tail withdrawal latency time in tail flick test, cold allodynia in acetone test and decrease motor power by grip strength test. Biochemically increased levels of MDA, IL6, decrease level of SOD in sciatic nerve tissue and histopathological myelin sheath loss, reduced numbers of Schwann cells, and epineural inflammatory cells infiltrates. However, treatment with canagliflozin20mg/kg, canagliflozin10mg/kg, Pregabalin, markedly improved the behavior of rats, and partially reversed the biochemical alterations that were histopathological validated. Conclusion: Treatment with canagliflozin could be a promising option for prevention of DPN.