P038. Enhancement of cytoprotective mechanisms in case of blockage of COX‑2 and introduction of L‑arginine in experimental colitis
1Lviv national medical univercity, biochemistry, Lviv, Ukraine
Background: Ulcerative colitis is one of the most common diseases of large intestine in human. It is indicative of increased expression of NO-synthases, predominantly of iNOS, and COX‑2. L‑arginine is the substrate for nitric oxide, and also for L‑ornithine which is the precursor for the synthesis of collagen and polyamines. Purpose of the research was to study the effect of blockage of COX‑2 activity with celecoxib combined with injection of L‑arginine on the cytoprotective and metabolic processes under experimental ulcerative colitis.
Methods: UC was modeled by 1ml of 4% acetic acid injected into rats' large intestine. In the MMLI were determined: area and degree of destructive changes (histologically), parameters of NO-synthase system, content of TBA products, activity of SOD, catalase and concentration of L‑arginine in the plasma of blood
Results: The development of UC was accompanied by the destructive changes in the MMLI, enhanced processes of LP, increased content of NO, and considerable activation of iNOS. Histological investigations revealed disorders of mucous barrier of the MMLI, destructive changes of its components, presence of edema, deep erosions, infiltration of lymphocytes.
Blocking COX‑2 by celecoxib in case of experimental colitis caused reduction of the area of ulcerogenic lesions to 54.9±14.1 mm2. Activity of general NOS reduced by 57% (p < 0.01), of iNOS by 58% (p < 0.01), NO content decreased by 29%, and content of TBA products decreased by 20%. Introduction of of L‑arginine in case of experimental colitis caused reduction of the area of ulcerogenic lesions to 41.5±28.7 mm2. Activity of general NOS reduced by 57% (p < 0.01), of iNOS by 54% (p < 0.01), NO content decreased by 29%, and content of MDA decreased by 20%. In combined action of introduction of L‑arginine with the blockage of COX‑2 by celecoxib, area of MMLI lesions considerably decreased and was 37.5±25.5 mm2 (p < 0.01). Activity of general NOS diminished to the norm and activity of iNOS by 74% (p < 0.01). Content of MDA and catalase was at the level of intact animals.
Conclusions: Combined blockage of COX‑2 and introduction of L‑arginine as determined in our investigations, strengthened their effects and tended to reduce iNOS activity, content of nitric oxide decreased, lipoperoxiation processes and activity of SOD in the MMLI diminished. This provides substantiation for new approaches to the treatment of ulcerative colitis and for development of the drugs capable of combined effect on iNOS and COX-2