Flurbiprofen and its nitric oxide-releasing derivative protect against septic shock in rats.
OBJECTIVE
Flurbiprofen and nitroflurbiprofen were evaluated in a caecal ligation puncture (CLP) model of septic shock in the rat.


RESULTS
CLP (12 h) reduced blood pressure (72.5 +/- 1.0 mm Hg c. f. 101.0 +/- 3.6 mm Hg, P < 0.05), and increased plasma NOx (153.0 +/- 11.5 muM c. f. 36.2 +/- 3.2 microM, P < 0.05), IL-1beta (534.0 +/- 93.1 pg/mL c. f.; 9.6 +/- 9.6 pg/mL, P < 0.05), TNF-alpha (88.0 +/- 13.6 pg/mL, P < 0.05), inflammatory damage in lung and liver, and mortality. Both flurbiprofen (21 mg/kg, p. o.) and nitroflurbiprofen (30 mg/kg, p. o.) prevented the fall in blood pressure (e. g. 80.4 +/- 2.1 mm Hg and 79.8 +/- 1.2 mm Hg respectively, 12 h, P < 0.05), reduced organ damage and prolonged survival. Nitroflurbiprofen (but not flurbiprofen) increased plasma NOx and reduced plasma TNF-alpha concentration at all time points (except 1 h). Neither drug affected plasma IL-1beta-levels.


CONCLUSIONS
These results suggest a protective effect of flurbiprofen and nitroflurbiprofen in septic shock.
Anuar
F
F
Department of Pharmacology, National University of Singapore, Block MD2, 18 Medical Drive, Singapore, 117597, Singapore.
Whiteman
M
M
Bhatia
M
M
Moore
P K
PK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C095631:nitroflurbiprofen; D009569:Nitric Oxide; D005480:Flurbiprofen