Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats

Abstract

Spinal cord injury (SCI) results in rapid and significant oxidative stress. This study was aimed to investigate the possible beneficial effects of Ebselen in comparison with Methylprednisolone in experimental SCI. Thirty six Wistar albino rats (200-250 g) were divided in to six groups; A (control), B (only laminectomy), C (Trauma; laminectomy + spinal trauma), D (Placebo group; laminectomy + spinal trauma + serum physiologic), E (Methylprednisolone group; laminectomy + spinal trauma + Methylprednisolone treated), F (Ebselen group; laminectomy + spinal trauma + Ebselen treated), containing 6 rats each. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T11-12. After this application, group A, B and C were not treated with any drug. Group D received 1 ml serum physiologic. Group E received 30 mg/kg Methylprednisolone and, Group F received 10 mg/kg Ebselen intraperitoneally (i.p.). Rats were neurologically examined 24 h after trauma and spinal cord tissue samples had been harvested for both biochemical and histopathological evaluation. All rats were paraplegic after SCI except the ones in group A and B. Neurological scores were not different in traumatized rats than that of non-traumatized ones. SCI significantly increased spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to control. Methylprednisolone and Ebselen treatment decreased tissue MDA and PC levels and prevented inhibition of the enzymes SOD, GSH-Px and CAT in the tissues. However, the best results were obtained with Ebselen. In groups C and D, the neurons of the spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in groups E and F were very well protected, but not as good as the control group. The number of neurons in the spinal cord tissues of the groups C and D were significantly less than the groups A, B, E and F. We concluded that the use of Ebselen treatment might have potential benefits in spinal cord tissue damage on clinical grounds.

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

“…However, the 30 mg/kg dose of ebselen did not significantly increase antioxidant enzyme activities. Our results were consistent with previous studies [21][22][23]30,31]. Therefore, we suggest that the protective effects of the 15 mg/kg dose of ebselen may be exerted via improvement of the antioxidant defense system in sciatic nerve I/R injury.…”

C60-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

“…Compound 3 was obtained in 42% yield (based on consumed C 60 ) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol. Its structure was confirmed by 1 H NMR, 13 C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C 60 derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 µmol L -1 ).…”

“…12 More recently, ebselen and its derivatives also confirmed to have neuroprotective effects on experimental rat spinal cord injury. 13 All these biological effects shown by ebselen and its analogues are obviously related to their antioxidative properties and free radical scavenge activities.…”

“…12 More recently, ebselen and its derivatives also confirmed to have neuroprotective effects on experimental rat spinal cord injury. 13 All these biological effects shown by ebselen and its analogues are obviously related to their antioxidative properties and free radical scavenge activities.In view of the above mentioned antioxidative and neuroprotective properties of both C 60 and ebselen derivatives, it is expected that the covalent attachment of the biologically active ebselen moiety to C 60 -fullerene may lead to the formation of a new C 60 -based ebselen derivative, which could present better antioxidative and neuroprotective properties than the parent C 60 or ebselen molecules. In this article we report the synthesis of the new C 60 -based ebselen derivative 3, which contains a solubilizing ethyleneglycol chain, by Bingel cyclopropanation involving C 60 and ebselen malonate.…”

“…O produto foi sintetizado em três etapas, partindo de cloreto de 2-cloro-selenobenzoila e 2-(2-aminoetoxietanol), com rendimento de 42% (baseado no consumo de C 60 ). O composto 3 foi caracterizado estruturalmente por análises espectroscópicas de RMN de 1 H e de 13 C, IV, UV e FAB-MS. Com o objetivo de verificar um possível aumento na atividade antioxidante e neuroprotetora do derivado 3, um derivado de C 60 (4), um derivado de ebselen (2) e sua mistura (4 + 2 em razão equimolar) foram selecionados para o tratamento de células neurais pelo mesmo procedimento adotado para 3 e na mesma concentração final (30 µmol L -1 ). As viabilidades celulares dos quatro grupos de tratamento foram estimadas por ensaios de LDH (desidrogenase láctica) e MTT (brometo de 3-[4,5-dimetil-tiazol-2-il]-2,5-difenil-tetrazólio).…”