The effects of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells.
In parallel studies, the effects of 5-aminosalicylic acid (5-ASA) and acetyl-5-aminosalicylic acid (acetyl-5-ASA) on peroxidation of red-cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5-ASA at concentrations of 10(-5), 10(-4) and 10(-3) M significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl-5-ASA had no effect. 10(-5) and 10(-4) M 5-ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2 alpha (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10(-4) M 5-ASA also significantly stimulated prostacyclin production measured as 6KF1 alpha by 10% (P < 0.05). At 10(-3) M 5-ASA there were significant falls in 6KF1 alpha (by 37%) PGE2 (by 45%) and PGF2 alpha (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl-5-ASA had little effect upon prostaglandin production. 5-ASA scavenges free radicals and stimulates production of cytoprotective prostaglandins.
Greenfield
S M
SM
Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London, UK.
Boswell
D J
DJ
Punchard
N A
NA
Thompson
R P
RP
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis / Q000097:blood; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D011464:Epoprostenol / Q000096:biosynthesis / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D019804:Mesalamine; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood
D000636:Aminosalicylic Acids; D016166:Free Radical Scavengers; D011453:Prostaglandins; D019804:Mesalamine; D008315:Malondialdehyde; C028836:N-acetyl-5-aminosalicylic acid; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone