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
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
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.
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