title: Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.
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.
authors.affiliation: Dumlupinar University, Faculty of Medicine, Department of Pharmacology, Kutahya, Turkey. filiz_ozyigit@mynet.com.
authors.forename: Filiz
authors.initials: F
authors.lastname: Ozyigit
authors.forename: Aysegul
authors.initials: A
authors.lastname: Kucuk
authors.forename: Sezer
authors.initials: S
authors.lastname: Akcer
authors.forename: Murat
authors.initials: M
authors.lastname: Tosun
authors.forename: Fatma Emel
authors.initials: FE
authors.lastname: Kocak
authors.forename: Cengiz
authors.initials: C
authors.lastname: Kocak
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kocak
authors.forename: Hasan
authors.initials: H
authors.lastname: Metineren
authors.forename: Osman
authors.initials: O
authors.lastname: Genc
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001393:Azoles / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D054833:Isoindoles; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D009569:Nitric Oxide; C042986:ebselen; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II