title: 5-Aminosalicylic acid inhibits leukotriene B4 omega-hydroxylase activity in human polymorphonuclear leukocytes.
abstract: omega-Oxidation is regarded as the major pathway for the metabolism and inactivation of leukotriene B4 (LTB4). To investigate the action of 5-aminosalicylic acid (5-ASA) on LTB4 omega-hydroxylase activity, we incubated human polymorphonuclear leukocytes (PMNLs) with 3H-labeled LTB4 after pre-incubation with various concentrations of 5-ASA. omega-oxidation metabolites were separated by high performance liquid chromatography and each radioactivity was measured by a liquid scintilation counter. LTB4 omega-hydroxylase activity was inhibited by 5-ASA in a concentration-dependent fashion. The 50% inhibitory dose was about 50 mumol/l, which is within the concentration range found in the colonic mucosa. Our findings may be valuable in elucidating the potentially critical aspect of 5-ASA treatment in ulcerative colitis (UC).
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ikehata
authors.forename: N
authors.initials: N
authors.lastname: Hiwatashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology*; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000201:enzymology; D042926:Cytochrome P-450 CYP4A; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007700:Kinetics; D015289:Leukotrienes / Q000378:metabolism*; D019804:Mesalamine; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000636:Aminosalicylic Acids; D065607:Cytochrome P-450 Enzyme Inhibitors; D015289:Leukotrienes; C057290:5-hydroxy-6-(2-keto-3-thiopropionyl)-7,9,11,14-eicosatetraenoic acid; D019804:Mesalamine; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A