The effect of 5‐aminosalicylic acid–containing drugs on sulfide production by sulfate‐reducing and amino acid–fermenting bacteria

• Published in: Inflammatory bowel diseases 2003-01, Vol.9 (1), p.10-17
• Main Authors: Edmond, Laurie M., Hopkins, Mark J., Magee, Elizabeth A., Cummings, John H.
• Format: Article
• Language: English
• Subjects: 5‐Aminosalicylic acid; Amino acids; Amino Acids - metabolism; Amino acid‐fermenting bacteria; Aminosalicylic Acids - chemistry; Aminosalicylic Acids - pharmacology; Aminosalicylic Acids - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Anti-Ulcer Agents - therapeutic use; Chemostats; Desulfovibrio - drug effects; Desulfovibrio - isolation & purification; Desulfovibrio - metabolism; Drugs; Feces - chemistry; Feces - microbiology; Fermentation - drug effects; Fusobacterium - drug effects; Fusobacterium - isolation & purification; Fusobacterium - metabolism; Humans; In Vitro Techniques; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - metabolism; Mesalamine - chemistry; Mesalamine - pharmacology; Mesalamine - therapeutic use; Metabolites; Phenylhydrazines; prodrugs; Pure culture; Sulfasalazine; Sulfasalazine - chemistry; Sulfasalazine - pharmacology; Sulfasalazine - therapeutic use; Sulfate; Sulfate-reducing bacteria; Sulfide; Sulfides - analysis; Three‐stage chemostat; Ulcerative colitis
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/00054725-200301000-00002

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.