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ORIGINAL RESEARCH ARTICLE

Luminal Antioxidants Enhance the Effects of Mesalamine in the Treatment of Chemically Induced Colitis in Rats

Hanumantha R. Ancha^*, Ravi R. Kurella^*, Christine C. McKimmey^*, Stanley Lightfoot and Richard F. HartY^*,1

^* Section of Digestive Diseases and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, and Oklahoma City Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104; and Section of Digestive Diseases and Nutrition, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104

To whom requests for reprints should be addressed at ¹ Department of Gastroenterology, University of Oklahoma Health Sciences Center, 920 SL Young Blvd. - WP 1360, Oklahoma City, OK 73104. E-mail: Richard-harty{at}ouhsc.edu

Previous experiments in rats with chemically induced colitis have shown that the antioxidant N-acetylcysteine plus mesalamine (5-ASA) exerted a significantly greater therapeutic effect in promoting mucosal healing when compared to either agent alone. The aims of the present study were to compare the effects of three antioxidants plus mesalamine vs. 5-ASA alone in treatment of colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats. Methods: Three days following induction of TNBS colitis, rats received 8 days of rectal therapy with 5-ASA, or 5-ASA plus vitamin C (ascorbic acid), 5-ASA plus phenyl butylnitrone (PBN) and 5-ASA plus vitamin E (-tocopherol). Distal colonic tissues were examined for microscopic colitis and myeloperoxidase (MPO) activity. Results: Global assessments of microscopic colitis induced by TNBS indicated that 5-ASA alone significantly changed colonic injury by –31%. Combination therapy with ascorbic acid plus 5-ASA or -tocopherol plus 5-ASA caused further significant change in TNBS colitis by –65 and –82%, respectively. Each of these values was significantly below scores observed with 5-ASA as monotherapy. Reduction in colitis with PBN plus 5-ASA was not different from 5-ASA alone. MPO activity was decreased significantly in response to monotherapy with 5-ASA and each of the antioxidants plus 5-ASA when compared to TNBS. -Tocopherol plus 5-ASA, however, was the only treatment strategy that reduced significantly MPO activity below that recorded for 5-ASA alone. In conclusion, our results indicate that antioxidants other than N-acetylcysteine significantly enhance the therapeutic effectiveness of 5-ASA in the treatment of TNBS colitis. -Tocopherol plus 5-ASA exerted profound anti-inflammatory and reparative effects upon colitis induced by TNBS.

Key Words: ascorbic acid • -tocopherol • phenyl butylnitrone • 5-ASA • colitis