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Inhibition of nitric oxide synthesis by aminoguanidine increases intestinal damage in the acute phase of rat TNB‐colitis
Author(s) -
Dikopoulos N.,
Nüssler A. K.,
Liptay S.,
Bachem M.,
Reinshagen M.,
Stiegler M.,
Schmid R. M.,
Adler G.,
Weidenbach H.
Publication year - 2001
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2001.00802.x
Subject(s) - nitric oxide , colitis , nitric oxide synthase , nitrite , lactate dehydrogenase , glutathione , chemistry , medicine , myeloperoxidase , inflammatory bowel disease , prostaglandin e2 , inflammation , pharmacology , endocrinology , immunology , biochemistry , enzyme , nitrate , disease , organic chemistry
The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel diseases (IBD) is controversially discussed. The aim of the present study was to investigate the role of NO inhibition in the acute phase of rat 2,4,6‐trinitrobenzenesulphonic acid (TNB)‐colitis. To inhibit NO synthesis we used aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS). TNB‐colitis was induced in rats with and without pretreatment with AG (200 mg kg −1 body weight in the drinking water). The severity of colitis was observed over a period of 7 days. On days 1 and 2, AG reduced concentrations of plasma nitrate and nitrite as well as of portal 6‐keto‐prostaglandin 1α. AG pretreatment increased colonic damage and inflammatory response, assessed by colonic myeloperoxidase and serum lactate dehydrogenase activity, macroscopic damage score, tumour necrosis factor‐α concentration in stool and colonic glutathione content. The AG‐treated group showed a higher and prolonged nuclear factor κB (NF‐κB)/Rel binding activity in the colon. We conclude that NOS inhibition by AG is not beneficial in acute intestinal inflammation. With regard to appropriate therapeutic strategies, NF‐κB/Rel activation might be a more suitable target.