Benoxaprofen, an inhibitor of arachidonic acid lipoxygenase, does not prevent aspirin sensitive asthma

Abstract

SCAVENGERS OF SUPEROXIDE. Edward J. McClain~ M.S. and Eric P. Brestel, M.D.~ Morgantown, West Virginia. Heparin has antiinflammatory effects in experimental nephritis in animals, and in rapidly-progressive glomerulonephritis in humans. It inhibits the local and generalized 8hwartzman reactions and reduces the inflammatory effects of histamine, bradykinin, and PGE I. Recent studies have shown heparin to inhibit phagocytosis and chemiluminescence (CL) in polymorphonuclear leukocytes (PMN's). Since CL is dependent on the superoxide ion (0~) and/ or its products, this study was undertaken to examine the ability of heparin to scavenge or inhibit the production of 02 in biological systems. Nitroblue tetrazolium (NBT) was used as an indicator of 02 production by the xanthinexanthine oxidase system. Heparin, dextran sulfate, polyanetholesulfonic acid, and SN 263 (a sulfated amylopectin) inhibited NBT reduction in this system in a dose responsive manner, causing 50% inhibition at a final concentration of 0.08, 0.07, 0.2, and 0.06 mg/ ml, respectively. These sulfated polysaccharides did not diminish uric acid production or alter the NBT absorption spectrum. Ferricytochrome C reduction by zymosan-activated human FMN's was inhibited by 50% by heparin at 1.95 mg/ml and dextran sulfate at 0.53 mg/ml. Dextran 500 was not inhibitory in either system. This observed ability of sulfated polysaccharides to scavenge O~ may explain some of their previously-observed antiinflammatory properties. BENOXAPROFEN, AN INHIBITOR OF ARACHIDONIC ACID LIPOXYGENASE, DOES NOT PREVENT ASPIRIN SENSITIVE ASTHMA. W.R. Lumry, M.D., J.G. Curd, M.D., W.E. Brocklehurst, Ph.D., R.A.-Simon, M.D. and D.D. Stevenson, M.D., La Jolla, California One hypothetical mechanism proposed to explain aspirin (ASA) sensitive asthma is that ASA inhibits cyclooxygenase and shunts arachidonic acid through the lipoxygenase pathway leading to increased production of leukotrienes (slow reacting substance). Benoxaprofen (BXP), a new nonsteroidal anti-inflammatory drug, selectively inhibits lipoxygenase at therapeutic plasma levels. The purpose of this study was to assess the effects of BXP in ASA sensitive asthmatic patients. Four ASA sensitive asthmatic patients underwent placebo controlled, blind ingestion challenges with BXP alone, ASA alone and ASA following 3-11 days of BXP 600 mg/d. Nasal/ ocular symptoms and pulmonary functions were monitored. A decrease in FEV l.O sec > 25% and/ or significant nasal/ocular congestion-was defined as a positive reaction. None of the 4 patients reacted to ingestion of BXP alone. All had positive reactions to ASA both before and after BXP treatment. There was no significant difference in the threshold ASA dose provoking the positive reaction, the delay time between ASA ingestion and reaction, or the type of reaction occurring before or after BXP treatment. Our study suggests that the shunting of arachidonic acid through the lipoxygenase pathway to leukotrienes (slow reacting substance) is not the principle mechanism for ASA provoked asthma in ASA sensitive asthmatic patients.