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.
2-(4-(2-Imidazo[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 micrometer) 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 micrometer) to the same degrees 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 micrometer) and phenylbutazone (100 micrometer). Dexamethasone, prednisolone, hydrocortisone and tinoridine hydrochloride (1--10 micrometer) inhibited more potently the PLC-induced release than the spontaneous release. Y-9213 (1--100 micrometer) 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 degrees C for 15 min was strongly inhibited by dexamethasone, prednisolone and hydrocortisone (1--100 micrometer), but not by Y-9213, phenylbutazone and indomethacin (100 micrometer). Y-9213 (0.1--10 micrometer) 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. Our results suggest that Y-9213 may stabilize membranes of erythrocytes and lysosomes and inhibit phagocytic secretion of lysosomal constitutents from PMN leukocytes.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology*; D010587:Phagocytosis / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013696:Temperature
D000893:Anti-Inflammatory Agents; D007038:Hypotonic Solutions; D010666:Phenylpropionates; C017978:miroprofen