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Effects of N-Acetylcysteine Plus Mesalamine on Prostaglandin Synthesis and Nitric Oxide Generation in TNBS-Induced Colitis in Rats

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Abstract

The aim of the present studies was to examine mechanisms by which the rectally administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA) affects inducers of inflammation to promote mucosal healing and reduce tissue inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA was superior to individual agents in reducing histological measures of colitis. NAC alone and in combination with 5-ASA suppressed COX2 gene expression and prostaglandin E2 (PGE2) levels to control values. Furthermore, NAC plus 5-ASA reduced nitrate generation, an expression of inducible nitric oxide synthase (iNOS) activity, to basal levels and these results were significantly lower than those observed with either NAC or 5-ASA alone. In conclusion, these results indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering the actions of PGE2 and the deleterious effects of oxidative and nitrosative stress induced by TNBS colitis.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center and Oklahoma City Department of Veterans Affairs Medical Center, 920 SL Young Blvd.-WP 1360, Oklahoma City, OK, 73104, USA

    Hanumantha R. Ancha, Ravi R. Kurella, Christine C. McKimmey & Richard F. Harty

  2. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Stanley Lightfoot

Authors
  1. Hanumantha R. Ancha
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  2. Ravi R. Kurella
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  3. Christine C. McKimmey
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  4. Stanley Lightfoot
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  5. Richard F. Harty
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Correspondence to Richard F. Harty.

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The authors thank Helen Prince for expert secretarial assistance in manuscript preparation.

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Ancha, H.R., Kurella, R.R., McKimmey, C.C. et al. Effects of N-Acetylcysteine Plus Mesalamine on Prostaglandin Synthesis and Nitric Oxide Generation in TNBS-Induced Colitis in Rats. Dig Dis Sci 54, 758–766 (2009). https://doi.org/10.1007/s10620-008-0438-0

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  • DOI: https://doi.org/10.1007/s10620-008-0438-0

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