Flurbiprofen and its nitric oxide-releasing derivative protect against septic shock in rats

Abstract.

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 μM c. f. 36.2  ±  3.2 μM, P < 0.05), IL-1β (534.0  ±  93.1 pg/mL c. f.; 9.6  ±  9.6 pg/mL, P < 0.05), TNF-α (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-α concentration at all time points (except 1 h). Neither drug affected plasma IL-1β-levels.

Conclusions

These results suggest a protective effect of flurbiprofen and nitroflurbiprofen in septic shock.