Biopolymers and Cell. 2011; 27 (2): 147 - 153

Comparison of dual acting drugs and conventional NSAIDs towards parameters of NO-synthase system and oxidative stress in mucosal membrane of large intestine of rats with experimental ulcerative colitis

A. Ya. Sklyarov¹, R. B. Lesyk², N. B. Panasyuk¹, I. S. Fomenko¹, D. Ya. Havrylyuk²

¹Department of Biochemistry Danylo Halytsky Lviv National Medical University
69, Pekarska St., Lviv, Ukraine, 79010

²Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University
69, Pekarska St., Lviv, Ukraine, 79010

Aim was to compare the action of 2A5DHT compound (dual COX-2/5-LOX inhibitor) and conventional non-steroidal anti-inflammatory drugs towards parameters of nitric oxide (NO) system and intensity of oxidative stress in the mucous membrane of the large intestine (MMLI) in rats with experimental ulcerative colitis. Methods. Ulcerative colitis was induced by administration of acetic acid. The activity of NO-synthases, content of NO, and parameters of lipoperoxidation processes were measured in MMLI. Results. COX-2/5-LOX inhibition by 2A5DHT compound did not cause considerable destructive changes of the MMLI of rats. The activity of inducible nitric oxide synthase (iNOS) declined more than 2 fold as compared to their activity in colitis. The intensity of lipoperoxidation processes was found to be much lower than under the separate effect of celecoxib or indomethacine. Conclusions. Dual COX-2/5-LOX inhibition by 2A5DHT has a significant cytoprotective effect in MMLI that is accompanied by reduction of oxidative stress and activity of NO-synthases. The substance 2A5DHT significantly overexceeds the cytoprotective effects of both selective and non-selective COX/LOX inhibitors and can be used in the treatment of inflammatory bowel disease.

Keywords: cyclooxygenase-2, 5-lipooxygenase, nitric oxide, lipoperoxidation, ulcerative colitis