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P191. Activity of nitric oxide-synthases and lipoperoxidation processes at the background of acetic acid-induced colitis due to amaranth oil introduced with aminoguanadine or celecoxib

N. Panasyuk IV

LNMU, Lviv, Ukraine

In ulcerative colitis lipoperoxidation processes and activity of NO-synthases intensify, and content of nitric oxide and proinflammatory cytokines in the mucous membrane of large intestine (MMLI) increases.

Purpose of the research was to study the effect of blockage of COX-2 activity with celecoxib or blockage of iNOS activity with aminoguanidin combined with injection of amaranth oil on the cytoprotective and metabolic processes under experimental ulcerative colitis.

Methods: Ulcerative colitis in rats (n = 80) was modeled with 4% acetic acid. In the MMLI homogenates were determined: content of TBA products and NO, activity of SOD, catalase, cNOS, iNOS and concentration of L-arginine and content of fatty acids in the plasma of blood.

Results: Injection of 4% acetic acid induced development of ulcerative defects, erosions, massive hemorrhages of the area of 90.4±27.5 mm2. Content of TBA products increased by 2.2-fold (p < 0.001), activity of SOD enhanced by 71%, of catalase – by 54% (p < 0.01), of general NOS – by 2.5-fold (p < 0.001), of cNOS – by 21%, of iNOS – by 6.9-fold, content of NO in the MMLI increased by 64% (p < 0.05). Concentration of L-arginine in the blood decreased by 51% (p < 0.001), due to normal condition.

Injection of amaranth oil caused reduction of the area of ulcerative lesions to 45.4±20.83 mm2. Activity of general NOS reduced by 52% (p < 0.01), iNOS activity – by 69% (p < 0.001), NO content decreased by 29%, and concentration of L-arginine in the blood increased by 23%. Content of TBA products decreased by 35% and catalase activity reduced by 27%.

In combined action of amaranth oil 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 activity – by 74% (p < 0.001), NO content decreased by 32%, and concentration of L-arginine in the blood increased by 34%. Content of TBA products and catalase activity was at the level of intact animals.

In combined action of amaranth oil with the blockage of iNOS by aminoguanidine, area of MMLI lesions decreased and was 38.8±30.1 mm2 (p < 0.01), activity of general NOS diminished to the norm and activity of iNOS – by 73% (p < 0.001), NO content decreased by 29%, and concentration of L-arginine in the blood increased by 40%. Content of MDA and catalase was at the level of intact animals.

Thus, combined action of celecoxib or aminoguanidine with amaranth oil manifests pronounced cytoprotective and anti-inflammatory effects in ulcerative colitis that is associated with a steep decline in the activity of NO-synthases and indexes of oxidative stress. Obtained results substantiate application of combined action of oils with high concentrations of unsaturated fatty acids and selective blockers of COX-2 in treatment of inflammatory processes.