P098. Action of hydrogen sulfide and NSAIDs on the activity of the NO-synthase system of the colon under the condition of stress
I. Fomenko, V. Yemelyanenko, A. Sklyarov, Danylo Halytsky Lviv National medical University, Biochemistry, Lviv, Ukraine
Stress and NSAIDS are the main factors that contribute to the development of the ulcerative colitis [Konturek P.C., Brzozowski, Konturek S.J., 2011; Predmore B.L., Lefer D.J., Gojon G., 2012]. Hydrogen sulfide (NaHS) prevents the destructive damage of the gastric mucosa [Wallace J.L., 2012]. The purpose of our study was the evaluation of the role of NO-synthase system under the influence of NaHS on the background of stress and action of NSAIDS.
The studies were conducted on 30 white rats weighing 180–250 g according to the ethical requirements concerning the work with the laboratory animals. The modeling of stress was performed using the model of water-immobilization stress (WIS) during 5 hours in fasting condition. In the homogenates of colonic mucous membrane (CMM) the activity of NO-synthases, the content of nitrite anion (NO2−) with the help of Griess reagent, content of MDA was determined. In blood plasma the concentration of L-arginine was detected. Nonselective blockers of COX-1/COX-2 naproxen (NAP) and selective blocker of COX-2 celecoxib (Cel) were administered intragastrically at a single dose 10 mg/kg, NaHS-.
Under the conditions of WIS during 5 hours the activity of inducible NO-synthase (iNOS), content of NO2- and TBA-active products increased in CMM (4.2-fold, P < 0.0; 12%, and 18% respectively), activity of constitutive NO-synthase (cNOS) and the concentration of L-arginine in blood plasma decreased (for 70% and 23%, P < 0.05 respectively) compared to the indices of the control group of animals. Introduction of NaHS on the background of WIS in CMM caused the decrease of iNOS activity by 20% (p < 0.05), when the activity of cNOS increased by 124% and content of TBA products did not change. Action of NAP under WIS in CMM decrease activity of iNOS by 42% (p < 0.05), when the activity of cNOS increased by 114% and content of TBA products did not change. Simultaneously introduction of NaHS with NAP on the background of WIS did not cause the change of NO-synthases activity and lipid peroxidation processes compared to the influence of NAP on the background of WIS.
The effect of NaHS inhibits iNOS activity and increases cNOS, whereas its influence simultaneously with COX-1/COX-2 blockage on the background of WIS did not cause significant changes in the mucosal membrane of the colon. NaHS did not affect the activity of lipid peroxidation processes. Maybe, the protective effect of NaHS under the conditions of stress is mediated by the increase of eNOS activity in endotheliocytes of the vessels and epitheliocytes of the colon.