Increasing anastomosis safety and preventing abdominal adhesion formation by the use of polypeptides in the rat

Tingstedt, Bobby; Nehéz, László; Axelsson, Jakob; Lindman, Björn; Andersson, Roland

doi:10.1007/s00384-005-0053-x

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…Postoperative adhesions in this study also significantly decreased, supporting our previous studies [11][12][13] . Bleeding per se do not cause development of adhesions, but is well known to predispose for adhesions with concurrent serosal injury [30] .…”

Section: Discussionsupporting

confidence: 81%

“…We have in previous studies shown a significant antiadhesive effect by using a combination of two differently charged polypeptides, poly-L -lysine and poly-L -glutamate [11,12] , in a standardized animal model for abdominal adhesions [15] . In another study, we demonstrated an improved anastomotic healing in the colon as measured by anastomotic burst pressure with a continued positive effect on preventing postoperative adhesions [13] .…”

Section: Discussionmentioning

confidence: 98%

“…A novel agent that would possess properties, which reduced bleeding, decreased the adhesive effect of the bleeding itself, as well as prevented against other post-operative adhesions would be of potential value. We have previously shown that differently charged bioactive polypeptides significantly prevent abdominal adhesion formation in the experimental setting [11][12][13] . During these experiments, we also noted as a possible side effect the prevention of bleeding from accidentally injured sites.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Bioactive Polypeptides on Bleeding and Intra-Abdominal Adhesions

Tingstedt¹,

Nehéz²,

Lindman

et al. 2007

Eur Surg Res

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Background:Perioperative bleeding and postoperative adhesions are two problems encountered in abdominal surgery. Commercial products are available that decrease both bleeding and development of abdominal adhesions, but no products are effective in both situations. The combination of differently charged bioactive polypeptides, administered intraperitoneally, has previously been shown effective in decreasing postoperative adhesions. The present study is a pilot examination of the effects on perioperative bleeding and postoperative adhesions, applying the polypeptide concept. Methods:Standardized wounds in the liver and spleen were induced in 52 NMRI mice. The amounts of bleeding and postoperative adhesions were measured after 1 and 7 days, respectively. Separate animals were examined after 8 weeks for long-term healing of the parenchymal wounds. Results:Both parenchymal bleeding and the extent of adhesions significantly decreased (p = 0.001 and p = 0.029, respectively) as compared to controls. Histology after 8 weeks showed no clear signs of impaired or altered healing. Conclusion:Intraperitoneal administration of differently charged polypeptides significantly decreased postoperative bleeding and postoperative adhesions. Bioactive polypeptides appear promising in the promotion of peritoneal healing and merits further studies.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Efficacy of Bioactive Polypeptides on Bleeding and Intra-Abdominal Adhesions

Tingstedt¹,

Nehéz²,

Lindman

et al. 2007

Eur Surg Res

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“…The antiadhesive effect of the polypeptides is based on electrostatic binding between the strong cation poly-L-lysine and the negatively charged damaged peritoneum [29], and thereafter electrostatic bonds between the poly-L-lysine and the anion poly-L-glutamate create a mechanical barrier between damaged and adhesionprone peritoneal tissue. The polypeptide matrix accumulates in areas of damaged peritoneum [16] and has also been shown to aid in intestinal healing as well as decreasing parenchymal bleeding and possibly inflammation [17,18,30].…”

Section: Discussionmentioning

confidence: 99%

“…In previous experimental studies we have shown very promising results in the reduction of postoperative abdominal adhesions using a combination of differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate [16][17][18]. The positively charged poly-L-lysine binds to the negatively charged damaged peritoneal surface and then attaches the negatively charged poly-Lglutamate to build a neutral matrix preventing adhesion formation [19].…”

Section: Introductionmentioning

confidence: 99%

Cationic polypeptides in a concept of oppositely charged polypeptides as prevention of postsurgical intraabdominal adhesions

Isaksson¹,

Åkerberg²,

Said³

et al. 2011

JBiSE

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Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-Llysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p < 0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-Llysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.

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In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-l-lysine and poly-l-lysine/poly-l-glutamate in rats

Isaksson

Åkerberg

Posaric-Bauden

et al. 2014

J Mater Sci: Mater Med

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The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

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Increasing anastomosis safety and preventing abdominal adhesion formation by the use of polypeptides in the rat

Cited by 8 publications

References 20 publications

Efficacy of Bioactive Polypeptides on Bleeding and Intra-Abdominal Adhesions

Efficacy of Bioactive Polypeptides on Bleeding and Intra-Abdominal Adhesions

Cationic polypeptides in a concept of oppositely charged polypeptides as prevention of postsurgical intraabdominal adhesions

In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-l-lysine and poly-l-lysine/poly-l-glutamate in rats

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