The antiinflammatory moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger

Abstract

Using a novel spectrophotometric assay to detect free radical scavengers, the effects of sulfasalazine, a compound frequently administered in the treatment of chronic inflammatory bowel disease, and its main metabolites, 5-aminosalicylic acid (5-ASA), sulfapyridine, and N-acetyl-5-ASA, were compared with biological antioxidants (nordihydroguaiaretic acid (NDGA), alpha-tocopherol, and ascorbic acid) and antiinflammatory salicylates (acetylsalicylic acid and sodium salicylate). The results show that 5-ASA, but neither sulfasalazine and its other metabolites, nor the salicylates, shares with the biological antioxidants the property of being a potent scavenger of free radicals. Since 5-ASA is formed in millimolar concentrations in the colon of sulfasalazine-treated patients this mode of action may explain the beneficial effect of sulfasalazine in inflammatory bowel disease. Locally formed 5-ASA may break the free radical chain reaction initiated and maintained by activated phagocytes, thus arresting the perpetuating tissue destruction. This mechanism may indicate a general potential for radical scavengers in chronic inflammation.

Antioxidant Properties of 5-ASA: Potential Mechanism for Its Anti-Inflammatory Activity

“…Because lipid peroxidation is not initiated by the superoxide-dependent, ironcaralyzed formation of hydroxyl radical in this system, the inhibitory effect of 5-ASA is due solely to its ability to scavenge peroxyl free radicals. These data agree with and extend the findings of Ahnfelt-Ronne and Nielson ( 19), who demonstrated potent scavenging of a nitrogen-centred free radical by 5-ASA (ICso 5 µM) but not by sulphasalazine or sulfapyridinc. Another property of 5-ASA that may contribute to its antioxidant activity is its ability to chelate iron.…”

Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat

“…Hence, in this study, 5-ASA may have reduced colonic inflammation by some other mechanism. Indeed, 5-ASA was shown to be a free radical scavenger in vitro [25], and several investigators have suggested this property is responsible for its therapeutic action in human inflammatory bowel disease [25][26][27]. Furthermore, NDGA, in addition to being a 5-1ipoxygenase inhibitor [28], is also a potent free radical scavenger [25,29].…”

New Diarylheptanoids from Alnus japonica and Their Antioxidative Activity

“…DPPH radical scavenging activity was determined by the method of Ahnfelt-Bønne and Nielsen 22) with a modification. A test sample (20 ml) was mixed with 980 ml of an ethanolic solution of 100 mM DPPH.…”