Effects of ebselen on ischemia/reperfusion injury in rat brain

Aras, Mustafa; Altaş, Murat; Meydan, Sedat; Nacar, Emel; Karcioglu, Murat; Ulutaş, Kemal Türker; Serarslan, Yurdal

doi:10.3109/00207454.2013.879581

Cited by 27 publications

(11 citation statements)

References 30 publications

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“…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.…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, the 30 mg/kg dose of ebselen significantly increased LPO accumulation compared with the sham group. The results of this study were consistent with previous studies [21][22][23]. Consequently, while the 15 mg/kg dose of ebselen pretreatment may be protective against sciatic nerve I/R injury by reducing LPO, the 30 mg/kg dose of ebselen appears to have little or no effect on LPO.…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2015

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

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

et al. 2015

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“…The majority of available inhibitors of this redox system are directed toward TrxR, but recently, specific inhibitors of Trx have been tested in humans: PX-12 is under clinical trial as and anticancer agent (Baker et al, 2013;Kirkpatrick et al, 1998;Ramanathan et al, 2011), and ebselen is under investigation as a postischemia and poststroke therapeutic (Aras et al, 2014;Yamaguchi et al, 1998;Zhao et al, 2002). PX-12 and ebselen (EBS) inhibit the BoNT/A-induced cleavage of SNAP25 in CGNs as detected by immunofluorescence ( Figure 3A) and by quantitative immunoblotting ( Figure 3B).…”

Section: Inhibitors Of Thioredoxin Prevent the Intoxication Of Neuronmentioning

confidence: 99%

Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins

et al. 2014

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Botulinum neurotoxins consist of a metalloprotease linked via a conserved interchain disulfide bond to a heavy chain responsible for neurospecific binding and translocation of the enzymatic domain in the nerve terminal cytosol. The metalloprotease activity is enabled upon disulfide reduction and causes neuroparalysis by cleaving the SNARE proteins. Here, we show that the thioredoxin reductase-thioredoxin protein disulfide-reducing system is present on synaptic vesicles and that it is functional and responsible for the reduction of the interchain disulfide of botulinum neurotoxin serotypes A, C, and E. Specific inhibitors of thioredoxin reductase or thioredoxin prevent intoxication of cultured neurons in a dose-dependent manner and are also very effective inhibitors of the paralysis of the neuromuscular junction. We found that this group of inhibitors of botulinum neurotoxins is very effective in vivo. Most of them are nontoxic and are good candidates as preventive and therapeutic drugs for human botulism.

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“…Therefore, in the present study, these two test compounds were each investigated separately and in combination for their ability to reduce the dermatoxicity of HN2. EB-1 is an anti-inflammatory antioxidant compound that is under investigation for reperfusion injury ( Aras et al, 2014 ), stroke ( Yamaguchi et al, 1998 ), hearing loss ( Kil et al, 2021 ) and bipolar disorder ( Singh et al, 2013 ). Previous research in our lab has shown the edema-reducing and anti-vesicant ( Lulla et al, 2014 ), anti-bacterial ( Chan et al, 2007 ), anti-fungal ( Billack et al, 2010 , Orie et al, 2017 ) and cyto-protective ( Hardej and Billack, 2007 , Pino and Billack, 2008 , Pino et al, 2013 ) properties of EB-1.…”

Section: Discussionmentioning

confidence: 99%

Combination of ebselen and hydrocortisone substantially reduces nitrogen mustard-induced cutaneous injury

Tumu

Cuffari

Billack

2021

Current Research in Toxicology

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Effects of ebselen on ischemia/reperfusion injury in rat brain

Abstract: Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.

Cited by 27 publications

References 30 publications

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

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

Thioredoxin and Its Reductase Are Present on Synaptic Vesicles, and Their Inhibition Prevents the Paralysis Induced by Botulinum Neurotoxins

Combination of ebselen and hydrocortisone substantially reduces nitrogen mustard-induced cutaneous injury

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