Plasma-activated solutions prevent peritoneal adhesion formation by regulating eNOS expression in mesothelial cells

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Surgical Innovation

Background:

• Peritoneal adhesions cause significant morbidity with limited therapeutic options.
• Current adhesion prevention strategies have inconsistent efficacy and potential side effects.
• Plasma-activated solutions (PAS) show potential for anti-inflammatory and healing effects, but their role in adhesion prevention requires investigation.

Purpose of the Study:

• To investigate the therapeutic potential of PAS in preventing peritoneal adhesion formation.
• To elucidate the underlying mechanisms of PAS in preventing peritoneal adhesions.

Main Methods:

• Established murine models for peritoneal adhesions (ischemic button and cecum-peritoneum abrasion).
• In vitro studies using human peritoneal mesothelial cells treated with LPS or TGF-β1 to model apoptosis and mesothelial-to-mesenchymal transition (MMT).
• Quantified apoptosis, ROS levels, MMT markers, and inflammatory cytokines; performed histological evaluations.

Main Results:

• PAS significantly reduced adhesion scores in both murine models (p < 0.01).
• In vitro, PAS decreased mesothelial cell apoptosis (p < 0.01) and suppressed MMT markers (N-cadherin, Vimentin; p < 0.05).
• PAS attenuated oxidative stress, including general ROS (p < 0.001) and mitochondrial ROS (p < 0.01), by restoring eNOS expression via reactive nitrogen species (RNS).

Conclusions:

• PAS effectively prevents peritoneal adhesions through RNS-mediated eNOS restoration.
• PAS suppresses key mechanisms including oxidative stress, apoptosis, and MMT.
• PAS represents a novel and promising therapeutic strategy for adhesion prevention with potential for clinical translation.