The Action of Cox/Lox Inhibitors on Antioxidant System and Morphological State of Rat’s Colon Mucosa Under the Conditions of Stress

Abstract

Introduction. Extensive, and often uncontrolled, use of cyclooxygenase (COX) inhibitors, as well as the psychological stress, are important factors of inflammatory diseases development in the digestive tract, including the large intestine. The activation of lipoperoxidation processes is one of the pathogenetic links of the development of ulcers, which can serve as a marker for both the intensity of inflammation and the onset of proinflammatory state. The aim of the study – to find out the influence of certain COX and lipoxygenase (LOX) inhibitors on the activi­ty of free radical oxidation and the morphological state of the colon mucosa (CM) under the conditions of their independent action and under the conditions of stress. Research Methods. A model of 5 hours water-immobilization stress was selected for the stress simulation, for inhibition of COX and LOX – naproxen, celecoxib and compound 2A5DHT, which were administered intragastrically, in a single dose of 10 mg/kg. The morphological study of CM and the determination of the antioxidant enzymes activity in the CM homogenates were conducted. Results and Discussion. The single action of naproxen caused increase of SOD, catalase, MPO activity and TBA-active products concentration in the CM. Similar changes were noted under the conditions of stress. Administration of naproxen under the conditions of stress caused the increase of SOD activity compared to WIS action and increase of TBA-active products concentration, activity of catalase and MPO compared to naproxen action. Conclusions. It was found that non-selective COX inhibition was accompanied by proinflammatory effect in the CM, likely based on the prooxidant action of the nonselective COX inhibitor, which was confirmed by the activation of SOD. Selective COX-2 inhibition and inhibition of COX-2/5-LOX showed an anti-inflammatory effect due to a more effective mechanism of action.