Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation.
The in vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-ASA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2-.) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochrome c (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2-. generating systems, 5-ASA being the most powerful (greater than 50% of inhibition in the PMNs system and greater than 70% in the X/XOD system at 10 microM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.
Gionchetti
P
P
Dipartimento di Biochimica, Università di Bologna, Italy.
Guarnieri
C
C
Campieri
M
M
Belluzzi
A
A
Brignola
C
C
Iannone
P
P
Miglioli
M
M
Barbara
L
L
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D019804:Mesalamine; D009504:Neutrophils / Q000378:metabolism; D013053:Spectrophotometry; D012460:Sulfasalazine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase; D014970:Xanthines
D000636:Aminosalicylic Acids; D016166:Free Radical Scavengers; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D012460:Sulfasalazine; D019804:Mesalamine; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate; C032587:olsalazine