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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2025; 71(2): 51-57


EFFECTS OF NF-ΚB AND NRF2 MODULATORS ON REACTIVE OXYGEN AND NITROGEN SPECIES PRODUCTION IN RAT HEARTS FOLLOWING SURGICAL TRAUMA UNDER PROLONGED STRESS

R.M. Ryabushko, V.O. Kostenko

  1. Poltava State Medical University, Ukraine
DOI: https://doi.org/10.15407/fz71.02.051


Abstract

This study is of great relevance due to the growing interest in understanding the mechanisms underlying cardiovascular complications following surgery and trauma, particularly in the context of posttraumatic stress disorder. A commonly used experimental model for the latter is single prolonged stress (SPS). This study investigated the effects of transcription factor modulators – specifically, ammonium pyrrolidinium dithiocarbamate, an inhibitor of NF-κB activation, and sul- foraphane, an Nrf2 inducer, on the production of reactive oxygen species (ROS) and nitrogen species (RNS) in the rat heart following surgical trauma under the influence of SPS. Experimental design: twenty-eight adult male Wistar rats were divided into four groups, group 1 was the control group (intact animals), while the others were subjected to laparotomy and SPS. The rats were administered isotonic sodium chloride solution (control II), ammonium pyrrolidine dithiocarbamate (76 mg/kg), and sulforaphane (10 mg/kg) via gavage for 7 days. The results demonstrated that surgical trauma under SPS resulted in a significant increase in superoxide anion radical (O₂⁻•) production in the heart driven by microsomal mono- oxygenases, nitric oxide synthase (NOS), the mitochondrial respiratory chain, and NADPH oxidase of leukocyte. There was also an increase in both total and inducible NOS activ- ity, a disruption in the coupling of its constitutive isoforms (cNOS), and a rise in peroxynitrite concentration. Ammonium pyrrolidinium dithiocarbamate and sulforaphane reduced O ₂⁻• generation by 41.7% and 37.2%, respectively, mitochondrial respiratory chain activity by 27.6% and 18.7%, and leukocyte NADPH oxidase activity by 32.3% and 24.1%. Inducible NOS activity also decreased by 30.6% and 51.9%. Sulforaphane significantly increased the cNOS coupling index by 130%, while ammonium pyrrolidinium dithiocarbamate showed no significant effect. In conclusion, both compounds reduce ROS and RNS production in the heart, with sulforaphane enhancing cNOS coupling, thereby preventing the enzyme from shifting towards O₂⁻• formation.

Keywords: transcription factors NF-κB and Nrf2; ammonium pyrrolidinium dithiocarbamate; sulforaphane; prolonged stress; post-traumatic stress disorder; reactive oxygen and nitrogen species; NO synthase; heart.

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