Ebselen lowers plasma interleukin-6 levels and glial heme oxygenase-1 expression after focal photothrombotic brain ischemia.
Heme oxygenase-1, an inducible heat shock protein, is upregulated by oxidative stress, and its expression is modulated by proinflammatory cytokines such as IL-1 and IL-6. In the present study, we investigated the effects of postlesional, orally applied ebselen, a neuroprotective antioxidant, on serum levels of IL-6 and cerebral heme oxygenase-1 expression following focal ischemia induced by photothrombosis. Ebselen (50 mg/kg body weight) was given 30 min postlesion to male Wistar rats. Animals were divided into four groups: sham-operated vehicle control (n = 9), sham-operated ebselen control (n = 8), lesioned vehicle control (n = 14), and lesioned ebselen-treated (n = 17). Ebselen treatment resulted in a significant lowering of IL-6 plasma levels (26 +/- 5 pg/ml) as compared with that seen in lesioned vehicle controls (48 +/- 9 pg/ml) at 24 h postlesion. In sham-operated rats IL-6 was not detectable. Heme oxygenase-1-positive glial cells were quantitated within topographically determined perilesional brain regions. Within the 0.5-mm-wide rim region directly associated with the lesion core, no differences in the amount of heme oxygenase-1-positive glial cells were found. However, in the more remote ipsilateral perilesional cortex, significantly fewer heme oxygenase-1-positive glial cells were present within the supragranular cortical layers of lesioned ebselen-treated rats compared to lesioned vehicle controls (P < 0.001). In sham-operated rats, no glial heme oxygenase-1 induction occurred. The results indicate that postlesional ebselen treatment lowered plasma IL-6 levels subsequent to a photothrombotic lesion concomitant with a lowering of the heme oxygenase-1 response in glial cells.
Department of Physiological Chemistry I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
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Gladilin
H J
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Bidmon
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Divanach
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Arteel
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Witte
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Zilles
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Sies
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D015850:Interleukin-6 / Q000097:blood*; D020767:Intracranial Thrombosis / Q000150:complications; D054833:Isoindoles; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000975:Antioxidants; D001393:Azoles; D015850:Interleukin-6; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C042986:ebselen; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1