Inhibition of phospholipase A2 activities and some inflammatory responses by the marine product ircinin.
The marine product ircinin has been tested for its effects on secretory and cytosolic phospholipase A2 (PLA2) activities in vitro as well as for inhibition of cellular functions in human neutrophils and inflammatory responses in mice. Ircinin inhibited Naja naja venom, human synovial recombinant, bee venom and zymosan-injected rat air pouch PLA2 with IC50 values in the microM range, similar to those of the known inhibitor scalaradial. On the other hand, ircinin was less active on cytosolic PLA2 from human monocytes and decreased potently the release of LTB4 in human neutrophils. This marine product affected weakly human neutrophil functions like superoxide generation and degranulation. In the zymosan-injected rat air pouch ircinin inhibited in vivo the activity of PLA2 present in exudates and reduced dose-dependently myeloperoxidase levels, whereas cell migration was inhibited only at the highest dose tested. This compound exerted a potent anti-oedematous effect after topical application in the mouse ear oedema test. Ircinin is a new inhibitor of PLA2 activity and our results suggest a potential role for this marine product as an inhibitor of inflammatory processes.
Cholbi
R
R
Department of Pharmacology, University of Valencia, Faculty of Pharmacy, Burjassot, Spain.
Ferrándiz
M L
ML
Terencio
M C
MC
De Rosa
S
S
Alcaraz
M J
MJ
Payá
M
M
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D006718:Homosteroids / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D017572:Leukotriene A4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D011161:Porifera / Q000737:chemistry*; D051381:Rats; D054830:Sesterterpenes; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D006718:Homosteroids; D017572:Leukotriene A4; D008387:Marine Toxins; D054830:Sesterterpenes; D013729:Terpenes; D013481:Superoxides; C071197:scalaradial; D010741:Phospholipases A; D054467:Phospholipases A2; D019272:Leukocyte Elastase