ROLE OF SPECIFIC TRANSCRIPTION FACTORS NF-κB AND NRF2 IN MECHANISMS OF DEVELOPMENT OF BRAIN-INJURY INDUCED OXIDATIVE AND NITROSATIVE STRESS

Abstract

This study is aimed at investigating the effect of specific modulators of transcription factors NF-κB and Nrf2 on indicators of oxidative-nitrosative stress in periodontal soft tissues in the early post-traumatic period after experimental model of moderate traumatic brain injury (TBI). The experiment was conducted on 20 white male Wistar rats weighing 180-220 g, divided into 4 groups: the 1st (pseudo-traumatized animals, control 1) exposed to the same manipulations (ether anaesthesia, fixation) as in the experimental series, with the exception of TBI modelling; the 2nd group – after TBI modelling (control 2); animals of the 3rd and 4th groups following the TBI modelling received intraperitoneal injections of modulators of transcription factors for 7 days: the inhibitor of NF-κB nuclear translocation ammonium pyrrolidine dithiocarbamate in a dose of 76 mg/kg and the inducer of the transcription factor Nrf2 dimethyl fumarate in a dose of 15 mg/kg in 10 % dimethylsulfoxide solution, respectively. The study has shown that at the end of the early post-traumatic period (on the 7th day), the modelled TBI is accompanied by the development of oxidative-nitrosative stress in the soft tissues of the periodontium that is confirmed by an increase in the production of the superoxide anion radical by all its main sources (microsomes, mitochondria and leukocyte NADPH oxidase), an elevation in NO-synthase activity due to the inducible isoenzyme whilst under the decreased activity of the constitutive isoform with its transition to the uncoupled state, and a growth in the concentration of peroxynitrite. The introduction of specific modulators of the transcription factors NF-κB and Nrf2 (ammonium pyrrolidine dithiocarbamate and dimethylfumarate, respectively) after TBI modelling significantly reduces the signs of oxidative-nitrosative stress in the periodontal soft tissues at the end of the early post-traumatic period (on the 7th day): it restricts the production of the superoxide anion radical, reduces NO-synthase activity due to the inducible isoform of this enzyme, enhances the activity and coupling of cNOS, and decreases the concentration of peroxynitrite.