5-Aminosalicylic acid inhibits leukotriene B4 omega-hydroxylase activity in human polymorphonuclear leukocytes.
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).
Ikehata
A
A
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Hiwatashi
N
N
Kinouchi
Y
Y
Ito
K
K
Yamazaki
H
H
Toyota
T
T
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
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