Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Zangiabadi Zangiabadi

doi:10.3844/ajptsp.2011.59.67

Abstract

Problem statement: Diabetes mellitus occurs mainly with chronic polyneuropathy, and oxidative stress plays an important role in emergence of most neurologic and behavioral changes in diabetic patients. Many studies have focused on the beneficial effects of various antioxidants such as melatonin on diabetic neuropathy. The aim of this study is to evaluate the effect of melatonin in prevention of neuropathy in Streptozotocin-induced diabetic rats. After prescribing Streptozotocin (STZ), treatment rats received melatonin (10 mg kg day-1) or DMSO for a period of 6 weeks. Approach: At the end of the sixth week, non diabetic control group, diabetic control group (sham) and treated rats were examined by thermal pain response tests (hot plate and tail flick). The horizontal and vertical activities of rats were measured in an open field test. After that, Motor Nerve Conduction Velocity (MNCV) of sciatic-tibial nerve recorded. Also, to study morphological alterations resulting from diabetic neuropathy of sciatic nerve, Myelinated Fiber Diameter (MFD), Axon Diameter (AD) and Myelin Sheath Diameter (MSD) were evaluated by light microscope. Results: According to hot plate results, response time to thermal pain at the end of sixth week in sham group showed a significant decrease in comparison with the control group (p<0.01). In hot plate test, although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the open field test, Total Distance Moved (TDM) and mobility duration showed significant decrease in sham and DMSO groups in comparison to the control and melatonin groups. Diabetic rats treated with melatonin showed significant increase in MNCV compared to sham and DMSO groups (p<0.05). In morphological study, pretreatment with Melatonin significantly reversed sciatic nerve diameters (MFD, AD, and MSD) reduction in diabetic rats. Electron microscopy showed myelin splitting and myelin sheath infolding in diabetic control group compare to non diabetic group. Conclusion: This study showed that melatonin can decrease the destructive progress of diabetes and causes neuroprotection against damages resulting from STZ-induced hyperglycemia.

Highlights

Hyperglycemia in diabetic patients as the main factor of diabetic neuropathy induces oxidative stress through various cellular pathways such as increasing aldose reductase activity (Srivastava et al, 2005), increasing glycation end-products (Sugimoto et al, 2008) and altering protein kinas C activity (Yamagishi et al, 2008)
Longstanding hyperglycemia through producing a large amount of Reactive Oxygen Species (ROS) can damage mitochondrial DNA in dorsal root ganglia leading to peripheral nerves dysfunction (Schmeichel et al, 2003)
There was no significant difference between the control group and none of the diabetic groups of sham, DMSO and melatonin in regard to the time spent in Statistical analysis: Data are presented as mean±SEM. central and border areas and immobility duration

Summary

INTRODUCTION

Hyperglycemia in diabetic patients as the main factor of diabetic neuropathy induces oxidative stress through various cellular pathways such as increasing aldose reductase activity (Srivastava et al, 2005), increasing glycation end-products (Sugimoto et al, 2008) and altering protein kinas C activity (Yamagishi et al, 2008). Tail flick latency there are few studies about its effect on prevention of was measured for three times and the average was diabetic neuropathy. It seemed that in this test, melatonin solvent (DMSO) has better protective effects than melatonin in Morphological study of sciatic nerve: For response to thermal pain. In evaluation of response to morphometric evaluation, sciatic nerve was isolated and thermal pain, there was no significant difference among divided into 2 mm segments They were fixed groups in tail flick test (Fig. 1). LSD test was used in At the end of the 7th week, MNCV showed significant morphological study and p

RESULTS

Findings

CONCLUSION