Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations

Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic activity that produces minor digestive side-effects. This fact induced us to think that LC is possibly a weak COX-1 inhibitor. In order to investigate our hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and control rats. Rat lung preparations incubated with 14C-arachidonic acid synthesise mainly PGE 2. LC at 2.5 and 4.1 × 10 −5 M does not modify the basal production of PGE 2 (probably COX-1) but at 6.8 × 10 −5 M significantly inhibited PGE 2 production (approximately 48.5% inhibition, P < 0.001). On the other hand, INDO at 10 −6 inhibited the basal production of PGE 2 by around 73%. In LPS-treated rats, the production of PGE 2 was significantly higher than in the lungs of control rats, probably due to the induction of COX-2. The addition of LC at 2.7 and 4.1 × 10 −5 M recovered the control values of PGE 2 inhibiting, probably only from COX-2 activity. LC at higher concentrations (6.8 × 10 −5 M) and INDO 10 −6 M inhibited PGE 2 formed by COX-2 and also partly by COX-1 activity.