Disease relevance of BW-755C

• To determine whether invading leukocytes mediate these responses, acute inflammatory cell influx was suppressed either by inducing leukopenia with nitrogen mustard or by administration of BW-755C, a mixed cyclooxygenase-lipoxygenase inhibitor [1].
• The protein inhibited edema when rats were pretreated with agents that depleted mast-cell amines, kininogen, or polymorphonuclear leukocytes prior to initiation of the carrageenin edema but had no inhibitory action when rats were pretreated with the dual cyclooxygenase/lipoxygenase inhibitor BW 755C [2].
• BW755C significantly reduced myocardial infarct size compared with that in control animals, as measured by infarct/risk areas by histochemical staining (39 +/- 5% vs. 63 +/- 7%, p < 0.05) [3].
• In 9 control and 10 study pigs pretreated with intravenous BW755C (10 mg/kg body weight) 30 min before coronary occlusion, ischemia was induced by a 50-min occlusion of the mid-left anterior descending coronary artery, followed by 3 h of reperfusion [3].
• Using mesentery, the effects were tested of BW755C, a lipoxygenase inhibitor, and of SM9064, a LTB4 receptor antagonist, upon the increase in leucocyte adherence observed during hypoxia [4].

High impact information on BW-755C

• Treatment with BW755C or dexamethasone was also accompanied by a reduction in total leukocyte numbers in inflammatory exudates collected at 1-14 days, whereas indomethacin increased leukocyte migration on days 1 and 2 and had no effect at later times [5].
• Preincubation with BW755C abolished the phosphorylation of the 26-, 29-, 32-, 40-, and 42-Kd proteins but not the 80- and 90-Kd proteins [6].
• MDC depleted of T cells were similarly inhibited by BW755C [7].
• BW755C, a dual inhibitor for cyclooxygenase and lipoxygenase activities, also inhibited hepatocyte growth [8].
• In the absence of leukocyte factors, the reaction catalyzed by the purified recombinant enzyme showed a half-time of maximal 5-HPETE formation of 0.5-0.7 min and was sensitive to the selective 5-lipoxygenase inhibitors BW755C (IC50 = 13 microM) and L-656,224 (IC50 = 0.8 microM) [9].

Chemical compound and disease context of BW-755C

• 2. Both the toxicity and the vasopermeability changes induced by endotoxin alone were blocked by the platelet-activating factor (PAF) antagonist BN52021, indomethacin or the dual cyclo-oxygenase/lipoxygenase inhibitor BW755C [10].
• We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis [11].
• The maximum pressor response to hypoxia measured at a blood flow of 50 ml.min-1. kg-1 averaged 26.6 +/- 2.4 Torr in untreated lungs and was not affected by BW 755C or 0.001-0.03 mM NDGA [12].
• Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema [13].
• Also, BW 755C did not block the pressor response to hypoxia in newborn sheep and goats, whereas the pressor response to LTD4 (75 ng/kg) was depressed significantly [14].

Biological context of BW-755C

• Inhibition of the cyclooxygenase and lipoxygenase pathways for AA metabolism by indomethacin or BW755C did not affect EIgG phagocytosis, demonstrating that these major AA metabolic pathways are not involved in phagocytic signaling [15].
• At a concentration of 0.03 mg/ml, BW755C inhibited degranulation (-46%), leukotriene B4 production (-48%) and superoxide generation (-74%), but there was minimal inhibition of chemotaxis in vitro [3].
• The inhibition of cyclo-oxygenase and lipoxygenase(s) by BW755C (75 microM) resulted in severe impairment in collagen-induced platelet aggregation [16].
• BW755C, a dual lipoxygenase/cyclooxygenase inhibitor, reduces mural platelet and neutrophil deposition and vasoconstriction after angioplasty injury in pigs [17].
• The mixed cyclo-oxygenase/lipoxygenase inhibitor compound BW 755C was very effective in blocking bronchoconstriction by the highest dose of FMLP used, but failed to interfere with leukopenia [18].

Anatomical context of BW-755C

• BW755C, a drug that inhibits both cyclooxygenase and lipoxygenase, dramatically inhibited eosinophil accumulation at 25 to 125 mg/kg [19].
• We here demonstrate that NK cell activity by human peripheral blood mononuclear cells (PBMC) against K562 or MOLT-4 target cells is rapidly and reversibly inhibited by two agents that inhibit the lipoxygenation of fatty acids, BW755C and nordihydroguaiaretic acid (NDGA) [20].
• Myocardial myeloperoxidase activity was similar in normal, salvaged and infarcted areas in the control and treated groups, indicating that neutrophil accumulation in injured myocardium was unaltered by BW755C [3].
• Natural killing (spontaneous cell-mediated cytotoxicity) by either human blood cells or mouse spleen cells is reversibly inhibited by nordihydroquaiaretic acid or BW755C, agents that antagonize the lipoxygenation of arachidonic acid [21].
• Preincubation of endothelium with lipoxygenase inhibitors nordihydroguaiaretic acid (50 microM), 5,8,11,14-eicosatetraenoic acid (50 microM), and BW755C (50 microM) inhibited the effect of phorbol preincubation of endothelium significantly by 55, 27, and 22%, respectively [22].

Associations of BW-755C with other chemical compounds

• In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively [23].
• In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively [23].
• In addition to histamine-H1 blockers, lipoxygenase inhibitors (nordihydroguaiarectic acid and BW 755C) and leukotriene blockers (FPL 55712 and LY 171883) are also potent inhibitors of CBE-induced RGC secretion [24].
• Phenidone and BW 755C are also to be cyclooxygenase inhibitors [25].
• Moreover, the inhibitory effect of 8-OH-DPAT on the carbachol response was blocked by 10 microM quinacrine (a phospholipase A2 inhibitor) but not by BW 755C (100 microM), a cyclooxygenase and lipoxygenase inhibitor [26].

Gene context of BW-755C

• Pretreatments with dexamethasone, BW 755C, BW A4C, WEB 2170, L-NAME, and monoclonal antibody (mAb) anti-interleukin-5 (IL-5; TRFK-5) had inhibited the eosinophil accumulation [27].
• The relaxation by ET-1 in the guinea pig taenia coli was not affected by treatment with NG-monomethyl-L-arginine, BW755C, or indomethacin [28].
• This effect was not altered by hexamethonium, indomethacin, BW755C or naloxone but was potentiated by leucine-thiorphan and inhibited by the tachykinin receptor antagonist (D-Pro2, D-Trp7,9)-SP and by atropine [29].
• For this purpose, human platelets pretreated with BW755C (a dual inhibitor of cyclooxygenase and lipoxygenase) were stimulated with collagen in the presence of varied concentrations of 15-HPETE [30].
• When indomethacin was present, NDGA, ETYA and BW755C (higher concentration) inhibited AVP-induced release of beta-E- and ACTH-IR [31].

Analytical, diagnostic and therapeutic context of BW-755C

• In animals treated with BW755C, renal allograft blood flow was maintained over the postoperative 5-day period at levels comparable to blood flow to the native kidneys [32].
• BW755C (10 mg/kg i.v., n = 10) significantly reduced this mural platelet deposition by more than 50% to 25.4 +/- 5.3 x 10(6)/cm2 (P < .05) and decreased 111In neutrophil deposition from 240.6 +/- 30.4 x 10(3)/cm2 in the control group to 114.4 +/- 20.4 x 10(3)/cm2 (P < .005) in the treated group [17].
• These results indicate that the dual lipoxygenase/cyclooxygenase inhibitor BW755C prevents the acute thrombotic and vasomotor responses related to arterial injury by angioplasty, predominantly through inhibition of neutrophil function [17].
• Thirty minutes before occlusion, animals randomly received BW755C, 3 mg/kg (n = 7), or 10 mg/kg (n = 8), or saline (n = 16) by intravenous infusion [33].
• Atropine and leukotriene inhibitors (LY171883 and BW755C) were not found to have a significant protective effect on WDE-induced constriction [34].

References