Effects of lipoxygenase inhibitors in arachidonate-induced sudden death.
Both BW 755c, a cyclo-oxygenase and lipoxygenase inhibitor, and nordihydroguaiaretic acid (NDGA), a selective lipoxygenase inhibitor, were tested for their protection against arachidonate-induced sudden death in rabbits. 100% survival was seen with BW 755c (1 mg kg-1), while NDGA showed 0 and 17% survival (2 mg kg-1 and 4 mg kg-1). BW 755c prevented 12-fold increase in plasma thromboxane B2 concentrations and the formation of pulmonary artery thrombi normally seen with arachidonate-induced sudden death, while NDGA showed no such protective effect. Radioimmunoassay of rabbit plasma for leukotrienes (LTC4, LTD4 and LTE4) indicated that they do not accumulate in blood in the model and BW 755c had no effect, suggesting that the deleterious effects seen are caused by cyclo-oxygenase pathway metabolites such as thromboxane A2, but not by lipoxygenase pathway products such as leukotrienes.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000506:poisoning*; D002396:Catechols / Q000494:pharmacology; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D003645:Death, Sudden / Q000209:etiology* / Q000473:pathology; D005966:Glucuronidase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009637:Masoprocol; D010179:Pancreas / Q000201:enzymology; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D002396:Catechols; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D005966:Glucuronidase; D002403:Cathepsins; D002402:Cathepsin D