Protective activity of ketoprofen lysine salt against the pulmonary effects induced by bradykinin in guinea-pigs

Abstract

We investigated the capacity of ketoprofen lysine salt (KLS) to counteract the pulmonary effects of some mediators of airway inflammation. The protective effect of KLS and its R-isomer against bradykinin (BK) induced plasma extravasation in the airways and bronchoconstriction was evaluated in anaesthetized guinea-pigs, in parallel with the capacity of KLS to inhibit the production of thromboxane A2 (TXA2). Moreover, we studied the ability of KLS to modulate leukotriene C4 (LTC4) and acetylcholine (ACH) induced bronchoconstriction and the associated production of TXA2. Nimesulide (NIM) was used as the reference compound. KLS dose-dependently inhibited the bronchoconstriction and the associated production of TXA2 induced by BK, with closely related ID50 values of 31.2 and 34.0 micrograms/kg i.v., respectively. The protection was evident 10 min after KLS administration and, at 100 micrograms/kg i.v., lasted up to 2h, Moreover, KLS dose-dependently inhibited the increase in capillary permeability induced by BK, with a potency (ID50 23.4 micrograms/kg i.v.) slightly higher than that shown against the bronchoconstriction. KLS also prevented the bronchoconstriction and TXA2 production triggered by LTC4, but not ACH induced bronchoconstriction. In all the models studied, KLS was about 10 times more potent than NIM. These data demonstrate the capacity of KLS to counteract the bronchoconstriction induced by BK and LTC4 and to a large extent the airway inflammation induced by BK. Blockade of prostanoid production is likely to account for this protective effect, since the R-isomer of KLS was devoid of significant activity.

Protective effect of ketoprofen lysine salt on interleukin-1β and bradykinin induced inflammatory changes in hamster cheek pouch microcirculation

“…In this regard, both topical and systemic ketoprofen have been proven to reduce crevicular fluid prostaglandin E 2 in adult periodontitis, possibly contributing to inhibition of disease progression [17]. The postulated mechanism of action lies not only in the inhibition of prostaglandin formation, but also in the ability of ketoprofen to antagonise some bradykinin activities, stabilise lysosomal membranes and suppress leukocyte migration [15,16,30]. In line with these data, we have demonstrated that topical KLS effectively and promptly counteracts both the increased number of sticking leukocytes and the microvascular leakage caused by IL-1b and BK in the hamster cheek pouch microcirculation.…”

“…The ability of KLS to modulate the bronchoconstriction induced by BK and to a larger extent the increase in airway permeability induced by BK has been reported to depend on cyclooxygenase blockade [16]. In this regard, topical ketoprofen has been recently shown to reduce gingival crevicular fluid prostaglandin E 2 levels in adult periodontitis [17] and to reduce the rate of alveolar bone loss in monkeys with ligature-induced oral inflammation [18].…”

Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition

“…Specific NSAIDs may be more useful than others. Ketoprofen, for example, may have substantial anti-bradykinin and anti-prostacyclin effects in addition to the typical anti-prostaglandin effect [ 141 ]. Inhibitors selective for cyclooxygenase-2 (e.g., celecoxib) have not been tested in CRPS, although are reported anecdotally to be of some use (level 4 evidence) [ 142–144 ].…”

Perspectives of Artrosilene (ketoprofen lysine salt) administration in rheumatologic practice

“…Блокадой продукции простано-идов авторы объясняют возможность купирования бронхоспазма в эксперименте [17].…”