INFLUENCE OF STAT-3 TRANSCRIPTION FACTOR INHIBITOR ON OXIDATIVE AND NITROSATIVE STRESS PARAMETERS IN PERIODONTAL TISSUES OF RATS EXPOSED TO SYSTEMIC LIPOPOLISACCHARIDE ADMINISTRATION

Abstract

This study is aimed at investigating the effect of imatinib mesylate, an inhibitor of the transcription factor STAT-3, on the oxidative and nitrosative stress indicators in rat periodontal tissues during the experimental systemic inflammatory response (SIR) induced by the introduction of the Salmonella typhi lipopolysaccharide (LPS) (in a dose of 0.4 μg/kg body wt, 3 times for the 1 week and once a week through the next 7 weeks). Imatinib mesylate introduction in a dose of 15 mg/kg 3 times a week, starting from the 30th day of the SIR modeling, was accompanied by a significant decrease in the rate of production of superoxide anion radical by the mitochondrial respiratory chain (by 13.4%) compared with the data from the SIR modeled group. The production rate of this radical by NADPH-dependent electron transport chains and phagocytes did not change significantly. At the same time, in the periodontal tissues, the total activity of NO synthase decreased (by 27.4%) without significant changes in the concentration of peroxynitrite ions. As a result, lipid peroxidation (LPO) in periodontal soft tissues was limited: the concentration of secondary peroxidation products before and after the incubation in a prooxidant buffer solution when imatinib mesylate was added was inferior to the results of the SIR modeled group by 37.5 and 33.8%, respectively. The activity of superoxide dismutase and catalase exceeded the data of the comparison group by 40.0 and 60.0%, respectively. It was concluded that the use of the inhibitor of STAT-3 activation, imatinib mesylate, under LPS-induced SIR, limits the formation of reactive oxygen and nitrogen species in rat periodontal tissues: it decreases the production rate of superoxide anion-radical by the mitochondrial electron transport chain, reduces the total activity of NO synthase. This results in the reduced formation of secondary LPO products in periodontal tissues and the reduced activity of antioxidant enzymes in them (superoxide dismutase, catalase).