A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy

Citation
Rcc. Chang et al., A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy, BRAIN RES, 854(1-2), 2000, pp. 224-229
Citations number
26
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
00068993 → ACNP
Volume
854
Issue
1-2
Year of publication
2000
Pages
224 - 229
Database
ISI
SICI code
0006-8993(20000131)854:1-2<224:ANEOAO>2.0.ZU;2-1
Abstract
Microglia as the first line of defensive cells in the brain produce free ra dicals including superoxide and nitric oxide (NO), contributing to neurodeg eneration. An opioid receptor antagonist, naloxone, has been considered pha rmacologically beneficial to endotoxin shock, experimental cerebral ischemi a, and spinal cord injury. However, the mechanisms underlying these benefic ial effects of naloxone are still not clear. This study explores the effect s of naloxone on the production of superoxide and NO by the murine microgli al cell line, BV2, stimulated with lipopolysaccharide (LPS) as measured by electron paramagnetic resonance (EPR). The production of superoxide trigger ed by phobol-12-myristate-13-acetate (PMA) resulted in superoxide dismutase (SOD)-inhibitable, catalase-uninhibitable 5,5-dimethyl-1-pyrroline N-oxide (DMPO) hydroxyl radical adduct formation. LPS enhanced the production of s uperoxide and triggered the formation of non-heme iron-nitrosyl complex. Ce lls pre-treated with naloxone showed significant reduction of superoxide pr oduction by 35%. However, it could not significantly reduce the formation o f non-heme iron-nitrosyl complex and nitrite. Taken together, the results e xpand our understanding of the neutroprotective effects of naloxone as it d ecreases superoxide production by microglia. (C) 2000 Elsevier Science B.V. All rights reserved.