Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response

Abstract

Chronic systemic inflammatory response syndrome (SIRS) underlies many diseases (sepsis, atherosclerosis, diabetes mellitus). According to research data of recent years the key role in the development of SIRS is played by the activation of various nuclear transcription factors. The work was aimed at studying the role of such transcription factor as activator protein 1 (AP-1) in the development of oxidative and nitrosative stress in soft periodontal tissues during chronic systemic inflammatory response (SIRS). The experiment was carried out on 24 the Wistar rats. We induced SIRS by bacterial lipopolysaccharide of Salmonella typhi (0.4 μg/kg) intraperitoneal injection. We studied changes in the functioning of the nitric oxide (NO) cycle, the production of superoxide anion radical (O 2•- ) and the activity of antioxidant enzymes in soft periodontal tissues homogenate. We used SR11302 as an Ap-1 inhibitor (15 mg/kg) for 2 months. We established that during the SIRS modeling, the activity of antioxidant enzymes in soft periodontal tissues decreased with a simultaneous increase in the production of O 2•- . SIRS elevated the production of NO by inducible NO-synthase (iNOS) and nitrite reductases. The nonoxidative cleavage of L-arginine under this condition was also increased. The concentration of peroxynitrite (ONOO - ) was shown to be elevated more than 2-fold. The inhibition of AP-1 by SR11302 normalized the functional state of the NO cycle, reduced O 2•- production and restored the activity of antioxidant enzymes. In this way, under SIRS conditions, “vicious circle” of ONOO - formation is formed. SIRS in soft periodontal tissues poses a threat of oxidative and nitrosative stress development. Usage of AP-1 activation inhibitor SR11302 breaks “vicious circle” of ONOO - formation.