The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors.
To determine if leukotrienes are important mediators of vascular permeability in brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier permeability in rats harboring HK Walker 256 brain tumors was examined using quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5-lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5-lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA-861. All three 5-lipoxygenase inhibitors significantly decreased vascular permeability both within the tumors and in brain adjacent to tumor. This suggests that capillary permeability in and adjacent to tumors is influenced by endogenous leukotrienes and that leukotrienes play an important role in brain tumor edema.
Brain Research Institute, University of California Medical Center, Los Angeles.
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D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D016227:Benzoquinones / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001932:Brain Neoplasms / Q000201:enzymology / Q000503:physiopathology*; D002279:Carcinoma 256, Walker / Q000503:physiopathology; D005260:Female; D015289:Leukotrienes / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D016227:Benzoquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D005723:gamma-Glutamyltransferase