Differently charged polypeptides in the prevention of post-surgical peritoneal adhesions.
OBJECTIVE
Peritoneal adhesions develop after almost all surgical interventions in the abdomen. We have developed an efficient treatment against post-surgical adhesions consisting of a combination of positively charged poly-L-lysine and negatively charged poly-L-glutamate. The aim of the present study was to further develop the concept of applying oppositely charged polypeptides in the prevention of adhesion formation, by evaluating different doses of the peptides, alterations in the way of administration, and also testing alternative components.


METHODS
Eighty-five NMRI mice were divided into six groups. A standardized peritoneal injury model was used. The groups received physiologic sodium chlorine, poly-L-lysine+poly-L-glutamate, low molecular weight poly-L-lysine+poly-L-glutamate, locally administered poly-L-lysine+poly-L-glutamate, in vitro mixed poly-L-lysine+poly-L-glutamate and poly-L-arginine+poly-L-glutamate, respectively. After 7 days, the extent of adhesion formation was determined during relaparotomy and was expressed as the mean percentage of the total wound length.


RESULTS
A significant decrease (p <0.001) in the peritoneal adhesion rate was detected in all groups, with the exception of the group administered poly-L-arginine. Among those animals that received poly-L-lysine and poly-L-glutamate, the low dose of poly-L-lysine administration resulted in the most pronounced anti-adhesive effect.


CONCLUSIONS
The most effective polypeptide combination was poly-L-lysine and poly-L-glutamate, also showing effectiveness when used at low doses and by local application. The differences in adhesion prevention and the possible underlying mechanisms are discussed and the key role of poly-L-lysine is elucidated.
Nehéz
László
L
Department of Surgery, Lund University Hospital, SE-221 85 Lund, Sweden.
Tingstedt
Bobby
B
Axelsson
Jakob
J
Andersson
Roland
R
D000818:Animals; D005260:Female; D007813:Laparotomy / Q000009:adverse effects*; D051379:Mice; D008970:Molecular Weight; D010455:Peptides / Q000627:therapeutic use*; D010532:Peritoneal Diseases / Q000209:etiology / Q000517:prevention & control*; D011099:Polyglutamic Acid / Q000627:therapeutic use*; D011107:Polylysine / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D000267:Tissue Adhesions
D010455:Peptides; D011107:Polylysine; C015462:polyarginine; D011099:Polyglutamic Acid