Ketoprofen and phenylbutazone attenuation of PAF-induced lung inflammation in calves.
The purposes of this study were: (1) to investigate which arachidonic acid metabolites contributed to platelet-activating factor (PAF) induced pulmonary dysfunction; and (2) to compare the effect of two non-steroidal anti-inflammatory drugs, phenylbutazone and ketoprofen in a model of PAF-induced reversible lung inflammation in six calves. In placebo and phenylbutazone groups, PAF infusion induced significant dysfunctions in the pattern of breathing, mechanics of breathing and gas exchange. These dysfunctions were prevented by ketoprofen pretreatment, except for the mechanics of breathing which was moderately but significantly altered by the PAF challenge. In all calves, leukotriene (LT) B4 plasma concentrations did not significantly increase above baseline values at any time. Prostaglandin (PG) E2 plasma concentrations showed a minor significant increase in phenylbutazone pretreated calves (55.8 +/- 25.8 pg/mL from 36.7 +/- 16.13 pg/mL). Thromboxane (TX) B2 plasma concentration was significantly increased during PAF challenge in placebo- and phenylbutazone-pretreated groups, but not in ketoprofen-pretreated calves (1580.0 +/- 1370 from 42.7 +/- 10.7 pg/mL; 2340 +/- 477 from 63 +/- 32 pg/mL; and 36.5 +/- 4.12 from 39.3 +/- 12.0 pg/mL, respectively). These data suggest that TXA2 is an important cyclooxygenase metabolite of arachidonic acid produced in response to PAF and that ketoprofen (intramuscular injection, 3 mg/kg) is more effective than phenylbutazone (intramuscular injection, 10 mg/kg) in preventing respiratory dysfunctions induced by the PAF challenge 30 min after drug administration. Ketoprofen did not suppress totally the PAF-induced changes in mechanics of breathing, which suggests that PAF or a secondary release of mediators could have a direct action on airway smooth muscle.
Laboratory for Functional Investigation, Faculty of Veterinary Medicine, University of Liege, Belgium.
M L
ML
Van de Weerdt
J
J
Coghe
C
C
Uystepruyst
G
G
Deby-Dupont
P
P
Lekeux
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D015232:Dinoprostone / Q000097:blood; D007660:Ketoprofen / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D010653:Phenylbutazone / Q000627:therapeutic use*; D010919:Placebos; D010972:Platelet Activating Factor; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*; D012119:Respiration; D013929:Thromboxane B2 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D013929:Thromboxane B2; D007660:Ketoprofen; D010653:Phenylbutazone; D015232:Dinoprostone