Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression Is Differentially Regulated to Favor a Pro-oxidant State That Contributes to Postoperative Adhesion Development

Abstract

We have previously reported that superoxide (O) contributes to the development of postoperative adhesions. In this study, we determined whether O generating nicotinamide adenine dinucleotide phosphate oxidase (NOX) is differentially expressed in normal peritoneal and adhesion fibroblasts and tissues. The NOX isoforms were measured utilizing Western blot, immunohistochemistry, high-performance liquid chromatography, and real-time reverse transcription polymerase chain reaction. Expression and activity of NOX were found to be significantly higher in adhesion tissues and cells than that in normal peritoneal tissues and cells (P < .05). Levels of NOX2, NOX4, NOX activating protein 1, DUOX1, p47, and p22 messenger RNA increased in adhesion fibroblasts when compared to normal peritoneal and increased in response to hypoxia in normal peritoneal fibroblasts. Thus, adhesion fibroblasts are characterized by a unique NOX expression profile, which maintains a pro-oxidant state that may be responsible for the persistence of the adhesion phenotype. Decreasing the activity of NOX by targeting these isoforms may be beneficial for future therapeutic interventions of postoperative adhesions.

The effect of pycnogenol on lymphatic nodes and adhesion during in a peritoneal adhesion model in rats

“…Bleeding, cauterization, ischemia, infections, and conditions that may damage the peritoneum may trigger adhesions [5][6][7] . While numerous cells such as mesothelial cells, histiocytes, fibroblasts, and lymphocytes help in healing the injured area, they also play a role in the development of peritoneal adhesion [2][3][4][5] . It has been demonstrated that adhesions are often the result of improper healing due to injured peritoneal tissues associated with oxidative stress 2 .…”

Pycnogenol prevents peritoneal adhesions

“…Adhesions are the result of an improper and uncontrolled healing process due mainly to oxidative stress-related damage to peritoneal tissues. Five to seven days post-operatively, the adhesive bands turn into vascular permanent fibrous adhesions [8][9][10][11][12][13][14][15][16][17].…”

“…The ethiopathogenesis of peritoneal adhesion formation is complex and involves inflammation, infection, ischemia, and oxidative stress [5,6,8,9]. Disequilibrium between the coagulation and fibrinolytic systems results in improper healing and peritoneal adhesive band formation between abdomino-pelvic organs [1,8].…”