Aim of the study was to evaluate the changes of lipid peroxidation processes, activity of enzymes of antioxidant defense and nitrite anion content in gastric mucosa and blood and concentration of gastrin and L-arginine in blood under the conditions of two-week blockage of Н+,К+-АTP-ase, COX-2 and CCK-2 receptors in rats.
The studies were carried out on 38 rats accordingly to international regulars on the work with laboratory animals. The animals were devided into 4 groups: 1) control – rats administered 1,0 ml saline; 2) rats administered the blocker of Н+,К+-ATP-ase lansoprazol (30 mg/kg); 3) rats administered lansoprazol and blocker of CCK-2 receptors proglumid (250 mg/kg); 4) rats administered lansoprazol and COX-2 blocker celecoxib (10 mg/kg).
Drugs were administered per os during 2 weeks. In gastric mucosa (GM) content of TBAactive products, nitrite anion, activity of superoxide dismutase (SOD) and catalase were determined; in blood – content of L-arginine and gastrin concentration. Statistical procession of the results and diagrams building were performed using programs Microsoft Excel, Statistica. The indices were supposed to be statistically significant when t value matched 95 % significance or р < 0,05.
Blockage of Н+,К+-АТP-ase during 2 weeks caused a 3.2-fold increase of gastrin concentration in blood (р < 0,01) compared to indices of the control group of animals. Under the mentioned above conditions, in GM the following was noted: 30 % (р < 0,05) decrease of the content of TBA-active products, SOD activity increased almost 2-fold (р < 0,01); whereas content of nitrite anion and catalase activity changed not significantly. In blood plasma a tendency to increase of SOD activity was observed and catalase activity decreased for 50% (р < 0,05), TBA-active products content did not change; L-arginine concentration decreased for 18 % (р < 0,05), compared to indices of the control group.
Decrease of lipid peroxidation processes may be mediated by the decrease of the level of metabolism in parietal cells, associated with the synthesis of hydrochloric acid, whereas the increase of SOD activity may be a result of increased activity of cyclooxygenase, which enzymatic activity is accompanied by the release of oxygen radicals.
Blockage of ССК-2 receptors by proglumid during 2 weeks on the background of inhibition of Н+,К+-АТPase resulted in the decrease of gastrin concentration in GM for 32 % (р < 0,05), what was accompanied by the increase of TBA-active products content for 14 %, decrease of the level of SOD activity for 44 % (р<0,05), in blood plasma dynamics to the decrease of SOD activity and increase of catalase activity was noted, compared to indices obtained under the effect of lansoprazol.
Blockage of COX-2 by celecoxib on the background of blockage of Н+,К+-АТPase resulted in the decrease of gastrin concentration in blood plasma for 51 % (р < 0,05). In GM, TBA-active products content increased for 55 % (р < 0,05), SOD activity decreased for 17 %; in blood plasma tendency to decrease of SOD activity and increase of catalase activity was noted compared to indices obtained under the conditions of the effect of lansoprazol. Obtained data showed that the system COX-2/PGE2 is involved in the development of hypergastrinemia. The close interrelationship exists between gastrin and COX-2/PGE2 system – gastrin activates COX-2 and subsequently production of prostaglandins.
Hence, 2 weeks-lasting blockage of ССК-2 receptors and COX-2 on the background of hypergastrinemia resulted in the decrease of gastrin concentration in blood plasma. Blockage of CCK-receptors and COX-2 causes the restoration of the level of lipid peroxidation processes and decrease of SOD in stomach.
Full text: PDF (Ukr) 848K