SEQUENTIAL EFFECTS OF AN ORAL ENZYME COMBINATION WITH RUTOSID IN DIFFERENT IN-VITRO AND IN-VIVO MODELS OF INFLAMMATION

The antiedematous and antiinflammatory potential of the proteolytic en zymes trypsin, chymotrypsin, bromelin and papain, and the flavonoid ru tosid were investigated in the following models: a) in vivo carrageeni n-induced rat paw edema; protein-induced paw edema; arachidonic acid-i nduced ear edema; passive cutaneous anaphylaxis; histamine-induced ski n reaction, and, b) in vitro arachidonic acid-induced platelet aggrega tion; protamine-induced degranulation; and, PAF-induced platelet aggre gation. Bromelin, chy motrypsin and papain demonstrated a strong antii nflammatory potential and were highly effective in the carrageenin-ind uced paw edema model. The effects were strongly correlated to the appl ied dose. Only papain demonstrated an antiexsudative effect (protein-i nduced ear edema). Bromelin showed a modulatory effect with regard to the arachidonic acid metabolism. Both bromelin and papain demonstrated a strong antihistaminic effect, which may be due to an inhibition of degranulation (antianaphylactic potency). An inhibitory potency could be observed for rutosid and trypsin with regard to the degranulation o f mast cells, No effects of the tested compounds were observed in the models of arachidonic acid-induced ear edema and PAF-induced platelet aggregation. A combination of these enzymes is at an advantage to show sequential synergy in inflammatory processes.