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

Abstract

There is a growing body of experimental data to rnggest chat the inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable source of these oxidants are the phagocytic leukocytes, since these cells are present in large numbers in the inflamed mucosa and are known to produce significant amounts of potentially injurious reactive oxygen species in response to inflammatory stimuli. The authors' laboratory and others have demonstrated that 5-aminosalicylic acid (5-ASA) possesses potent antioxidant activity, including free radical scavenging properties and the ability to decompose neutrophilic oxidants (eg, hypochlorous acid) and detoxify he,noprotein-associated oxidizing agents. 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. Therefore, it is proposed that much of the anti-inflammatory activity of 5-ASA may be due to its numerous antioxidant properties. CanJ Gastroenterol 1990;4(7):295-302 Key Words: Etiology , Intestinal injury , Neutrophils, Oxidants Les proprietes antioxydantes de l'acide 5-aminosalicylique: Mecanisme possible de son activite anti-inflammatoire RESUME: Des donnees experimentales de plus en plus nombreuses suggerent que l'intestin ou le colon irrite est peuc-ecre assujetti a un stress oxy<latif considerable. II est probable que les oxy<lants responsables proviennent des leucocytes phagocyraires qui abondent clans la muqueuse enflammee: on sait en effet qu'ils produisent, en reaction aux stimuli inflammato ires, des quantites considerables d'especes oxygenees reactives potentiellemenr nuisibles. Les etudes effectuees en laboratoire, par les auteurs et d'autres chercheurs, demontrent que l'acide 5-aminosalicylique (5-ASA) est un antioxydant puissant; ii a la capacite d'eliminer les radicaux libres, de decomposer les oxydants neutrophiles (acide hypochloreux) et de detoxifier l'hemoproteine associee aux agents oxydants. Le 5-ASA a de plus la propriete de chelater le fer et d'en affaiblir !'action oxydoreductrice. C'est pourquoi ii est suggcre que !'action anti-inflammatoirc du 5-ASA serait due en grande partie a scs nombreuses proprietes ant1oxydantes.

Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: A multicenter study

“…Ulcerative colitis (UC) is a recurrent inflammation of the colon and rectum that is characterized by rectal bleeding, diarrhea, fever, anorexia, and weight loss [1]. In active UC, there is activation and extravasation of large numbers of granulocytes and monocytes/macrophages into the colonic mucosa [1,2].…”

“…In active UC, there is activation and extravasation of large numbers of granulocytes and monocytes/macrophages into the colonic mucosa [1,2]. The infiltrated leukocytes can cause extensive mucosal tissue injury by releasing degradative proteases [2][3][4], reactive oxygen derivatives [2,[4][5][6][7], and proinflammatory cytokines [4,8,9].…”

5-Aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells

“…While the inhibitory activities of 5-ASA were observed at high concentrations (6–10 mM), the mucosal concentrations of 5-ASA30 were found to be very much lower (5–400 μM), comparable with the IC 50 for the efficacy of 5-ASA scavenging of oxidants, supporting the scavenging mechanism 29. Scavenging of HOCl was observed here at 5-ASA:HOCl ratios expected in vivo and comparable with those that provided protection of essential thiols on α 1 -antiprotease inhibitor13 and cysteine10 from oxidation by HOCl.…”

“…The mechanisms of action of 5-ASA in the inflamed mucosa in vivo have been difficult to elucidate because 5-ASA inhibits multiple inflammatory processes in vitro ranging from the inhibition of cyclo-oxygenase and lipoxygenase pathways to scavenging of inflammatory cell derived oxidants 29. While the inhibitory activities of 5-ASA were observed at high concentrations (6–10 mM), the mucosal concentrations of 5-ASA30 were found to be very much lower (5–400 μM), comparable with the IC 50 for the efficacy of 5-ASA scavenging of oxidants, supporting the scavenging mechanism 29.…”

The Role of Transient Mucosal Ischemia in Acetic Acid-Induced Colitis in the Rat

“…of drugs for the treatment of ulcerative colitis, as this substance possesses numerous antioxidant properties However, the rate of OFR generation may exceed the capacity of this defense system [13]. Thus, the adminis- [26,27].…”