EFFECT OF TRANSCRIPTION FACTOR MODULATORS ON OXIDATIVE-NITROSATIVE STRESS INDICATORS IN TISSUES OF THE SMALL INTESTINE OF RATS AFTER LAPARATOMY UNDER LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

Abstract

This study is devoted to investigating the effect of NF-κB and Nrf2 transcription factor modulators on oxidative-nitrosative stress indicators in the tissues of the small intestine of rats after abdominal surgical trauma (laparotomy) under lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The study was performed on 35 Wister white male rats weighing 220-250 g, divided into 5 groups: the 1st (control) group included "sham-operated" animals; the 2nd group involved rats, who underwent laparotomy following the LPS-induced SIR modelling; the animals of the 3rd, 4th and 5th groups subjected to laparotomy following LPS-induced SIR and then for 7 days received ammonium pyrrolidine dithiocarbamate, an NF-κB activation inhibitor, in a dose of 76 mg/kg intraperitoneally, dimethyl fumarate, an Nrf2 inducer, in a dose of 15 mg/kg in 10% dimethyl sulfoxide solution, and a water-soluble form of quercetin in a dose of 100 mg/kg that is 10 mg/kg in terms of quercetin, respectively. The measurements were carried out in 7 days after the “sham” surgical operation and laparotomy. It has been found out that the use of ammonium pyrrolidine dithiocarbamate, dimethyl fumarate, and water-soluble form of quercetin in case of the combined effects of surgical trauma (laparotomy) and LPS S. typhi significantly restrains the production of superoxide anion radical by various sources (microsomes and constitutive isoforms of NO-synthase, leukocyte NADPH-oxidase), total and inducible NO-synthase activity, formation of peroxynitrite in the tissues of the small intestine of rats. The study has also demonstrated the ability of dimethylfumarate, unlike ammonium pyrrolidine dithiocarbamate and quercetin, to improve the constitutive synthesis of nitric oxide under experimental conditions.