Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages

Citation
B. Hinz et al., Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages, PHARM RES, 18(2), 2001, pp. 151-156
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACEUTICAL RESEARCH
ISSN journal
0724-8741 → ACNP
Volume
18
Issue
2
Year of publication
2001
Pages
151 - 156
Database
ISI
SICI code
0724-8741(200102)18:2<151:FEIINO>2.0.ZU;2-H
Abstract
Purpose. Using RAW 264.7 macrophages, the present study investigates the in fluence of optically pure enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen on lipopolysaccharide (LPS)induced inducible nitric oxid e synthase (iNOS) expression. Methods. iNOS and cyclooxygenase-2 (COX-2) mRNA levels were measured by qua ntitative rear-time reverse-transcription polymerase chain reaction (RT-PCR ). Concentrations of nitrite (index of cellular NO production) and prostagl andin E-2 (index of COX-2 activity) in cell culture supernatants were deter mined by Griess assay and enzyme immunoassay, respectively. Results. R(-)- and S(+)-flurbiprofen decreased LPS-induced iNOS mRNA and ni trite levels in an equipotent and concentration-dependent manner. Suppressi on of iNOS mRNA expression by R(-)and S(+)-flurbiprofen was gene-specific i n that both substances failed to inhibit LPS-induced COX-2 mRNA expression. By contrast, flurbiprofen enantiomers suppressed LPS-induced prostaglandin E-2 formation enantioselectively with S(+)-flurbiprofen being considerably more potent than its R(-)-antipode. Conclusions. Our results show that R(-)- and S(+)-flurbiprofen, albeit diff ering in their potency as inhibitors of COX-2 activity, equipotently suppre ss iNOS expression. Because sustained high NO levels are associated with pa in and tissue injury under various pathological conditions, a suppression o f the inducible NO pathway may contribute to the pharmacological action of both R(-)- and S(+)-flurbiprofen.