New light on the anti-colitic actions of therapeutic aminosalicylates: the role of heme oxygenase.
Although a variety of pharmaceutical preparations of aminosalicylate are commonly used in the clinic for the control of inflammatory bowel disease, the mechanisms underlying their therapeutic actions remain unclear. Recent in vivo and in vitro studies have demonstrated that 5-aminosalicylic acid (5-ASA), regarded as the active moiety in aminosalicylate preparations such as sulfasalazine, can induce the heat shock protein, heme oxygenase-1 (HO-1) and up-regulate HO enzyme activity in the colon. As HO-1 can produce endogenous anti-oxidant and anti-inflammatory moieties such as bilirubin and carbon monoxide (CO), these findings suggest a novel mechanism of action for aminosalicylates, acting as anti-colitic agents through the up-regulation of HO-1 enzyme expression and activity.
Whittle
Brendan J R
BJ
The William Harvey Research Institute, Barts and the London School of Medicine, Charterhouse Square, EC1M 6BQ, London, UK. b.j.whittle@qmul.ac.uk
Varga
Csaba
C
D000636:Aminosalicylic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D019804:Mesalamine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D051381:Rats; D015854:Up-Regulation
D000636:Aminosalicylic Acids; D000975:Antioxidants; D019804:Mesalamine; D051547:Heme Oxygenase-1