Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies.
BACKGROUND
The therapeutic efficacy of 5-aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties.


OBJECTIVE
To compare in vitro the antioxidant effects of conventional drugs (5-aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4-aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N-acetylcysteine, glutathione, verapamil).


METHODS
Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell-free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol-amplified chemiluminescence.


RESULTS
5-aminosalicylic acid and balsalazide were more potent antioxidants than 4-aminosalicylic acid or N-acetyl-5-aminosalicylic acid in cell-free systems. 5-aminosalicylic acid (20 mM) and balsalazide (20 mM) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4-aminosalicylic acid (20 mM). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 mM) inhibited chemiluminescence by 100% in cell-free systems and by 60% in rectal biopsies. N-acetyl cysteine (10 mM), and both oxidized and reduced glutathione (10 mM), completely inhibited chemiluminescence in cell-free systems, but not with rectal biopsies.


CONCLUSIONS
The antioxidant effects of compounds varies between cell-free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy.
Simmonds
N J
NJ
The Gastrointestinal Science, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Millar
A D
AD
Blake
D R
DR
Rampton
D S
DS
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000368:Aged; D010131:Aminosalicylic Acid / Q000494:pharmacology; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002474:Cell-Free System; D003092:Colitis / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008163:Luminescent Measurements; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology; D008875:Middle Aged; D010659:Phenylhydrazines; D011349:Proctitis / Q000378:metabolism*; D013256:Steroids
D000305:Adrenal Cortex Hormones; D000636:Aminosalicylic Acids; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D010659:Phenylhydrazines; D013256:Steroids; D008795:Metronidazole; D019804:Mesalamine; D010131:Aminosalicylic Acid; C038637:balsalazide