Abstract
Background: Abdominal adhesions develop on damaged peritoneal surfaces and constitute a significant health related problem. Previous animal studies have shown promising anti-adhesive effects when administering the polycation α-poly-L-lysine (αPL) and the polyanion poly-L-glutamate (PG) together. The objective of the study was to examine the effect of these differently charged polypeptides when administered by spraying and to evaluate any possible effect on fibrinolysis, fibrosis and inflammation. Methods: Rabbits were treated with PLPG after cecal abrasive surgery and analysis from peritoneal biopsies of active tPa/PAI-1 complex and from peritoneal fluid of IL-6 and active TGFb1 at day 0, 1, 4 and 10 were measured after surgery. Histological specimens were analyzed on day 10 regarding inflammation and fibrosis. Peritoneal adhesions were evaluated by adhesion score. All values were compared to the control group (NaCl). Results: PLPG-treated rabbits had a significant diminished adhesion score on day 10 as compared to the control group (p < 0.005). Significantly reduced collagen depositions on the peritoneum were seen in the PLPG group when evaluating the histological specimens (p < 0.05). No significant differences between the experimental and control groups were seen in peritoneal fluid when analyzing for active protein levels. Conclusion: This is the first study to investigate the effect on key parameters in adhesion formation as well as the preventive effect of the PLPG complex on abdominal adhesions in rabbits and also the first study where administration by spraying the polypeptides was used. PLPG was non-toxic in this setting and without significant differences in adhesion formation parameters and a significant reduction in adhesions was observed. This was verified both macroscopically and histologically.
Highlights
Abdominal adhesions constitute a major clinical challenge causing small bowel obstruction [SBO], abdominal pain, female infertility and a high annual cost for healthcare [1,2]
Decreased tissue plasminogen activator and elevated levels of plasminogen activator inhibitor-1 (PAI-1) resulting in diminished fibrinolysis along with extended fibrosis associated with increased transforming growth factor beta (TGF-b) and higher amounts of inflammatory cytokines such as IL1-6 are all part of the local peritoneal adhesion formation [9,10,11]
This study aimed to investigate the anti-adhesive effect of the α-poly-L-lysine and α-poly-L-glutamate complex in a rabbit model and its possible effect on local peritoneal adhesion formation by measuring the active tPa/PAI-1 complex, TGFb1 and IL-6
Summary
Abdominal adhesions constitute a major clinical challenge causing small bowel obstruction [SBO], abdominal pain, female infertility and a high annual cost for healthcare [1,2]. Results: PLPG-treated rabbits had a significant diminished adhesion score on day 10 as compared to the control group (p < 0.005). No significant differences between the experimental and control groups were seen in peritoneal fluid when analyzing for active protein levels. Conclusion: This is the first study to investigate the effect on key parameters in adhesion formation as well as the preventive effect of the PLPG complex on abdominal adhesions in rabbits and the first study where administration by spraying the polypeptides was used. PLPG was nontoxic in this setting and without significant differences in adhesion formation parameters and a significant reduction in adhesions was observed. This was verified both macroscopically and histologically
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