Effects of 2-{4-(2-Imidazo[1,2-a]Pyridyl)Phenyl} Propionic Acid (Y-9213) and Anti-Inflammatory Drugs on Erythrocytes, Polymorphonuclear Leukocytes and Lysosomes in Vitro

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Abstract
2-{4-(2-Imidazol[1,2-a]pyridyl)phenyl}propionic acid (Y-9213) with analgesic, antipyretic and anti-inflammatory activities significantly inhibited hemolysis of rat erythrocytes. Activity of Y-9213 (100-500 .mu.M) on hemolysis was more potent than that of phenylbutazone, and less potent than that of indomethacin. The spontaneous release of enzymes from rat liver lysosomes by incubation alone was significantly inhibited by Y-9213 (1-100 .mu.M) to the same degree as phenylbutazone or tinoridine hydrochloride. Release of enzymes from the lysosomes by addition of phospholipase C (PLC, 0.03 units/ml) was slightly inhibited by Y-9213 (10-100 .mu.M) and phenylbutazone (100 .mu.M). Dexamethasone, prednisolone, hydrocortisone and tinoridine hydrochloride (1-10 .mu.M) inhibited more potently the PLC-induced release than the spontaneous release. Y-9213 (1-100 .mu.M) inhibited considerably the release of enzymes from intact lysosomes of rabbit polymorphonuclear (PMN) leukocytes. The release of enzymes from the PMN leukocyte lysosomes preincubated at 37.degree. C for 15 min was strongly inhibited by dexamethasone, prednisolone and hydrocortisone (1-100 .mu.M), but not by Y-9213, phenylbutazone and indomethacin (100 .mu.M). Y-9213 (0.1-10 .mu.M) also inhibited significantly the phagocytic secretion of lysosomal enzymes from PMN leukocytes without affecting phagocytosis of the particles. Activity of this agent was similar to that of phenylbutazone, and less active than that of indomethacin, dexamethasone or prednisolone. Y-9213 may stabilize membranes of erythrocytes and lysosomes and inhibit phagocytic secretion of lysosomal constituents from PMN leukocytes.

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