Bromelain-induced edema in the rat paw and effects of drugs Bromelain-induced edema in

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1 JAPANESE JOURNAL OF INFLAMMATION ORIGINAL ARTICLE Bromelain-induced edema in the rat paw and effects of drugs Bromelain-induced edema in rats was studied and compared to carrageenin-induced edema. The edema reached a maximum 30 min after Bromelain was injected subcutaneously into the rat paw, then decreased slowly, and had almost disappeared 24 hr later. The bromelain-induced edema was obviously potentiated by the oral administration of captopril, a kininase II inhibitor, 1 hr before and after the bromelain was injected; the carrageenin-induced edema was moderately but not dose-dependently potentiated. Dexamethasone suppressed the bromelain-induced and carrageenin-induced edema, but onset of the effect was slow. Nonsteroidal acidic anti-inflammatory agents (indomethacin, piroxicam, phenylbutazone, mefenamic acid, timegadine, and benoxaprofen), except aspirin, exerted no effect on the bromelain-induced edema, whereas they significantly reduced the carrageenin-induced edema. Nonsteroidal nonacidic anti-inflammatory agents such as emorfazone, aminopyrine, tiaramide, perisoxal, and paracetamol, significantly inhibited both types of edema. Antihistamine, antiserotonin, and diuretic agents did not affect the bromelain-induced edema, but diuretic agents inhibited the carrageenin-induced edema. These results indicate that the bromelain-induced edema may be mediated mainly by bradykinin, but not by metabolites of the arachidonic acid cascade or not by biogenic amines, and that the carrageenin-induced edema is mediated predominantly by prostaglandins. The bromelain-induced edema appears to be a useful model to evaluate the effects of nonsteroidal nonacidic anti-inflammatory agents. Shigeru Morimoto ESeiji Kuzuna EYoshitaka Maki *) * Biology Laboratories, Central Research Division, Takeda Chemical Ind. Ltd. key words: bromelain-induced edema, bradykinin, anti-inflammatory activity, nonsteroidal nonacidic anti-inflammatory agents, rat

2 \1 effects of captopril, steroidal and nonsteroidal acidic anti-inflammatory drugs on bromelain-and carrageenin-induced paw edema in rats }1 time course of the bromelain-induced paw edema in rats and potentiation by captopril, a kininase II inhibitor Bromelain (0.1 mg/paw) was injected into the subplantar region of right hind paw.

3 }2 effects of dexamethasone, indomethacin, aspirin and emorfazone on the bromelain-induced paw edema in rats. Drugs were administered orally 1 hr before bromelain was injected. }2 effects of nonsteroidal nonacidic anti-inflammatory drugs on bromelain-and carrageenin-induced paw edema in rats }3 effects of antihistamine, antiserotonin, diuretic and other drugs on bromelain- and carrageenininduced paw edema in rats

4 \4 effects of pre- or post-treatment with captopril, dexamethasone, aspirin and emorfazone on bromelain-induced paw edema in rats * P<0.05. ** P<0.01 vs control Test compounds were administered orally 1 hr before or 1 hr after bromelain was injected.

5 1) Blackwell, G.J., Carnuccio, R., DiRosa, M., Flower, R.J., Langham, C.S.J., Parente, L., Perisico, P., Russell-Smith, N., Stone, D.: Glucocorticoids induce the formation and release of anti-inflammatory and anti-phospholipase proteins into the pritoneal cavity of the rat. Br. J. Pharmacol. 96: 185, ) Moncada, S., Vane, JR.: Pharmacology and endogenous roles of prostaglandin endoperoxidase, thromboxane A2 and prostacyclin. Phrmacol. Rev. 30: 293, ) Collier, H.O.J., Lee, I.: Nociceptive responses of guinea-pigs to intradermal injection of bradykinin and kallidin 10. Br. J. Pharmacol. 21: 155, ) Suda, H., Yamauchi, H., Iso, T.: Potentiative effects of a kininase II inhibitor (YS980). on carrageenin induced edema in rat hind paw and roles of plasma kininogen. J. Pharm. Pharmacol. 34: 60, ) Suda, H., Nakata, K., Komura, T., Yamauchi, H., Iso, T.: Potentiative effects of sulfhydryl compounds on carrageenin induced edema in rats(v). Jpn. J. Inf. 2: 459, ) Ohishi, S., Uchida, Y., Ueno, A., Katori, M.: Bromelain, a thiolprotease from pineapple stem, depletes high molecular weight kininogen by activation of hageman factor (Factor XII). Thrombosis Res. 14: 665, ) Katori, M., Ikeda, K., Harada, Y., Uchida, Y., Tanaka, K., Ohishi, S.: A possible role of prostaglandins and bradykinin as a trigger of exudation in carrageenin-induced rat pleurisy. Agents Actions 8: 108, ) DiRosa, M., Giround, J.P., Willoughby, D.A.: Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenin and turpentine. J. Pathol. 104: 15, ) Winter, C.A., Risley, E.A., Nuss, G.W.: Carrageenin induced oedema in the hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exp. Biol. Med. 111: 544, ) Erdos, E.G.: The kinins -A status report-. Biochem. Pharmacol. 25: 1563, ) Sofia, R.D., Nalepa, S.D., Vassar, H.B., Knoblock, L.C.: Comparative anti-inflammatory activity of 9-tetrahydrocannabinol, hydrocortisone and aspirin in various rat paw edema models. Life Sci. 15: 251, ) Clark, M.A., Bomalaski, J.S., Conway, T.M., Wartell, J., Crooke, ST.: Differential effects of aspirin and dexamethasone on phospholipase A2 and C activities and arachidonic acid release from endothelial cells in response to bradykinin and leukotriene D4. Prosta. 32: 703, 1986.