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Published on: September 24, 2020
Flurbiprofen and its nitric oxide-releasing derivative protect against septic shock in rats
F Anuar1, M Whiteman, M Bhatia
1Department of Pharmacology, National University of Singapore, Block MD2, 18 Medical Drive, Singapore, 117597, Singapore.
Objective:
Flurbiprofen and nitroflurbiprofen were evaluated in a caecal ligation puncture (CLP) model of septic shock in the rat.
Methods And 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.
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