Spin trapping agent, phenyl N-tert-butylnitrone, reduces nitric oxide production in the rat brain during experimental meningitis

Citation
H. Endoh et al., Spin trapping agent, phenyl N-tert-butylnitrone, reduces nitric oxide production in the rat brain during experimental meningitis, FREE RAD RE, 35(5), 2001, pp. 583-591
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL RESEARCH
ISSN journal
1071-5762 → ACNP
Volume
35
Issue
5
Year of publication
2001
Pages
583 - 591
Database
ISI
SICI code
1071-5762(2001)35:5<583:STAPNR>2.0.ZU;2-M
Abstract
Phenyl N-tert-butylnitrone (PBN) is a spin trapping agent previously shown to exert a neuroprotective effect in infant rat brain during bacterial meni ngitis. In the present study, we investigated the effect of systemic PBN ad ministration on nitric oxide (NO) production in a rat model of experimental meningitis induced by lipopolysaccharide (LPS). We assessed the NO concent ration in rat brain tissues with an electron paramagnetic resonance (EPR) N O trapping technique. In this model, rats receiving intracisternal LPS admi nistration showed symptoms of meningitis and cerebrospinal fluid (CSF) pleo cytosis. The time course study indicated that the concentration of NO in th e brain reached the maximum level 8.5 h after injection of LPS, and returne d to the control level 24 h after the injection. When various doses of PBN (125-400 mg/kg) were injected intraperitoneally 30 min prior to LPS, NO pro duction in the brain was reduced with increasing PBN dose (250 mg/kg suppre ssed 80% at 8.5 h after LPS injection), and white blood cells (WBC) in CSF were significantly decreased. We concluded that reduction of NO generation during bacterial meningitis contributes to the neuroprotective effect of PB N in addition to its possible direct scavenging of reactive oxygen intermed iate (ROI).