Oxytocin provides protection against diabetic polyneuropathy in rats

Abstract

Purpose: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats.

Materials and methods: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 μg/kg OT or 160 μg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed.

Results: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 μg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group.

Conclusion: Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.

Keywords:

• Diabetes mellitus
• Diabetic polyneuropathy
• Oxytocin
• EMG
• Oxidative stress

Abbreviations:

• DNP: Diabetic polyneuropathy
• OT: Oxytocin
• STZ: Streptozotocin
• CMAPs: Compound muscle action potentials
• NCV: Neuron conduction velocity
• EMG: Electromyography
• ROS: Reactive oxygen species
• GSH: Glutathione
• TBARS: Thiobarbituric acid reactive substance
• MDA: Malondialdehyde
• TBARS: Thiobarbituric acid reactive substance
• TNF-α: Tumor necrosis factor- alpha
• PKC: Protein kinase C
• DRG: Dorsal root ganglion