EFFECTS OF MODULATING NF ΚB AND NRF2 SIGNALING PATHWAYS ON THE DEPOLYMERIZATION OF CONNECTIVE TISSUE BIOPOLYMERS IN THE RAT SMALL INTESTINE UNDER SURGICAL TRAUMA FOLLOWING SINGLE PROLONGED STRESS

Abstract

This study aimed to investigate the effects of ammonium pyrrolidinedithiocarbamate (an inhibitor of NF κB activation) and sulforaphane (an inducer of the Nrf2/antioxidant response element (ARE) signaling pathway) on the depolymerization processes of connective tissue biopolymers in the rat small intestine under conditions of surgical trauma following a single prolonged stress (SPS) model. Materials and methods. This experimental study was conducted using 28 white male Wistar rats (210–230 g), divided into four groups. Group 1 (Control I) consisted of intact animals. The remaining three groups underwent laparotomy following SPS modeling and then subsequently received daily intraperitoneal injections for seven days of one of the following solutions: isotonic sodium chloride (placebo, Control II), ammonium pyrrolidinedithiocarbamate (76 mg/kg), or sulforaphane (10 mg/kg). In the small intestine homogenates, biomarkers of the extracellular matrix biopolymer degradation were measured using a ULAB 101 spectrophotometer (China). Specifically, the study assessed free hydroxyproline (a marker of collagen breakdown), hexuronic acids (an indicator of glycosaminoglycan degradation), and N‑acetylneuraminic acid (a marker of sialoglycoprotein structural impairment). Results. Administration of ammonium pyrrolidinedithiocarbamate significantly reduced the degradation of connective tissue biopolymers, as evidenced by decreases in the levels of free hydroxyproline by 22.7%, hexuronic acids by 21.7%, and N acetylneuraminic acid by 22.1%, compared to Control II (P < 0.001). Sulforaphane also demonstrated a notable protective effect, resulting in reductions of free hydroxyproline by 18.5%, hexuronic acids by 17.6%, and N acetylneuraminic acid by 15.3% relative to the placebo group (P < 0.001). Conclusions. NF‑κB activation plays a key role in initiating the degradation of the extracellular matrix within the connective tissue of the small intestine. Inhibition of NF κB by ammonium pyrrolidinedithiocarbamate significantly limits the depolymerization of collagen, glycosaminoglycans, and sialoglycoproteins. Activation of the Nrf2/ARE signaling pathway through sulforaphane administration also exerts protective effects by attenuating the breakdown of connective tissue biopolymers, highlighting the importance of this endogenous antioxidant and cytoprotective mechanism.

Keywords

• transcription factors
• acute stress
• post-traumatic stress disorder
• surgical trauma
• laparotomy
• connective tissue
• collagen
• proteoglycans
• glycoproteins
• the small intestine