The effect of 5-aminosalicylic acid-containing drugs on sulfide production by sulfate-reducing and amino acid-fermenting bacteria.
The toxic, bacterial metabolite sulfide is implicated in ulcerative colitis. Ulcerative colitis patients taking 5-aminosalicylic acid-containing drugs have lower fecal sulfide levels than those not taking these drugs. The effects of sulfasalazine, balsalazide, olsalazine, and 5-aminosalicylic acid on sulfide production were studied in a three-stage chemostat pulsed on days 1 to 3 with 5 g sulfasalazine (40 mM) and in pure cultures of amino acid-fermenting and sulfate-reducing bacteria. By the third day of sulfasalazine addition to the chemostat, sulfide concentrations in vessels 1 through 3 had dropped from 1.73, 1.78, and 1.43 mM to 0.01, 0.15, and 0.9 mM, respectively. In pure cultures, 50% inhibition of sulfide production from amino acids occurred at 2.5 +/- 0.05 mM for sulfasalazine, 5 +/- 0.2 mM for olsalazine, 6 +/- 1 mM for balsalazide, and more than 20 mM for 5-aminosalicylic acid. Fifty percent inhibition of sulfide production from sulfate occurred at 0.25 +/- 0.05 mM for sulfasalazine, 0.7 +/- 0.2 mM for balsalazide, and 9.0 +/- 1.0 mM for 5-aminosalicylic acid. The order of effectiveness of equimolar concentrations of drugs (most effective first) in this assay was sulfasalazine, then olsalazine (though given clinically at half the dose of other 5-aminosalicylic acid prodrugs) and balsalazide, and lastly 5-aminosalicylic acid. Inhibition of sulfide production by 5-aminosalicylic acid-containing drugs may contribute to their therapeutic effect in ulcerative colitis.
Edmond
Laurie M
LM
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee, Scotland. L.M.Edmond@dundee.ac.uk
Hopkins
Mark J
MJ
Magee
Elizabeth A
EA
Cummings
John H
JH
D000596:Amino Acids / Q000378:metabolism*; D000636:Aminosalicylic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003901:Desulfovibrio / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005285:Fermentation / Q000187:drug effects*; D005673:Fusobacterium / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D019804:Mesalamine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010659:Phenylhydrazines; D012460:Sulfasalazine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013440:Sulfides / Q000032:analysis*
D000596:Amino Acids; D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010659:Phenylhydrazines; D013440:Sulfides; D012460:Sulfasalazine; D019804:Mesalamine; C038637:balsalazide; C032587:olsalazine