Effects of anti-inflammatory drugs on rat hind-paw swelling caused by phospholipase A2 from Naja naja atra venom.
Rat hind-paw swelling was induced dose-dependently by subplantar injection of acidic phospholipase A2 (NNAVPLA2) from Naja naja atra venom. Diphenhydramine and methysergide pretreatment greatly reduced the swelling effect caused by NNAVPLA2. Several doses of compound 48/80 given to deplete the histamine content of rat hind paw, also greatly suppressed NNAVPLA2-induced paw swelling. The paw swelling caused by NNAVPLA2 was reduced following pretreatment with BW 755C, a dual inhibitor of cyclooxygenase/lipoxygenase, or subplantar co-injection with FPL 55712, a SRS-A antagonist, while pretreatment with acetylsalicylic acid had no effect. Captopril significantly potentiated the NNAVPLA2-induced paw swelling. The recovered myeloperoxidase activity was increased within 1 h and still elevated in the rat paw 3 to 6 h after subplantar injection of NNAVPLA2. In isolated peripheral PMN leukocyte suspension, NNAVPLA2 caused a release of superoxide radical. Subplantar co-injection with superoxide dismutase/catalase significantly inhibited NNAVPLA2-induced paw swelling. NNAVPLA2 did not trigger platelet aggregation either in platelet-rich plasma or in washed platelet suspension. NNAVPLA2-induced hind-paw swelling was also suppressed by the pretreatment with isoprenaline or terbutaline, while this response was not affected by co-injection with BN 52021, a PAF antagonist, into the paw. It is concluded that the hind-paw swelling caused by NNAVPLA2 is mainly due to histamine and serotonin released from mast cells and partly due to the formed kinins and SRS-A in the inflammatory area, and superoxide radical from PMN leukocytes.
Department of Medical Research, Taichung Veterans General Hospital, ROC.
J P
JP
Wang
C M
CM
Teng
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D004546:Elapid Venoms; D006632:Histamine / Q000502:physiology; D007705:Kinins / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D010741:Phospholipases A; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004546:Elapid Venoms; D007705:Kinins; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D012701:Serotonin; D006632:Histamine; D010741:Phospholipases A; D054467:Phospholipases A2; D001241:Aspirin