Abstract

Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (p<0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (p<0.01, p<0.05, respectively), and increased SOD, GPx, and CAT activities (p<0.001, p<0.01, p<0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (p<0.01, p<0.05, p<0.001) and MDA and NO levels (p<0.05, p<0.01) and decreased SOD, GPx, and CAT activities (p<0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

Highlights

  • Ischemia plays a major role in the development of pathological changes in many neuropathies

  • We investigated the effectiveness of ebselen in protecting the sciatic nerve against Ischemia and reperfusion (I/R) injury, using biochemical, immunohistochemical, and histopathological analyses

  • Sciatic nerve tissue samples were fixed in 10% formalin, embedded in paraffin, sectioned (4 μm), placed on slides, stained with hematoxylin and eosin (H&E), and examined under a light microscope (Olympus BX51, Tokyo, Japan) by a pathologist who was blinded to the treatment groups

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Summary

Introduction

Ischemia plays a major role in the development of pathological changes in many neuropathies. Vascular occlusive diseases, and trauma are some pathologic conditions which cause neuropathy associated with ischemia of peripheral nerves [1]. A nerve must have a continuous and sufficient oxygen supply through intrinsic and extrinsic microvascular systems to carry out its normal functions [2]. Ischemia and reperfusion (I/R) causes ischemic fiber degeneration and oxidative injury in peripheral nerves. Schwann cells are the main target of oxidative injury due to I/R [3].

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