Effect of 5-lipoxygenase inhibitors on in situ LTB4 biosynthesis following calcium ionophore stimulation in the rat pleural cavity.
The intrapleural injection of carrageenan in the rat induces exudate formation, cellular influx and leukotriene generation in the pleural cavity. We have demonstrated that the inflammatory response (exudate volume, and LTB4 levels) is increased in situ by the intrapleural administration of calcium ionophore A 23187 (100 nmol/rat) at 4, 16, 24, 48, and 72 h after the injection of carrageenan and that the A 23187-induced increase is dose-dependent. The oral administration of A-64077 and MK-886, two 5-lipoxygenase inhibitors (5-LOIs), at 10 mg/kg causes marked decreases in LTB4 release at the above-mentioned time intervals. However, A 23187-induced augmented exudate formation is not affected by the treatment with 5-LOIs. The results suggest that the use of 5-LOIs to inhibit LTB4 biosynthesis may be beneficial in various LTB4-dependent pathological conditions.
Raychaudhuri
A
A
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
Chertock
H
H
Peppard
J
J
White
W D
WD
Koeler
J
J
DiPasquale
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D010994:Pleura / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D002722:Chlorobenzenes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000001:Calcimycin; D002351:Carrageenan; D006918:Hydroxyurea; D007211:Indoles; D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes; C063449:zileuton