Novel treatment in peritoneal adhesion prevention: Protection by polypeptides

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

doi:10.1080/00365520600554550

Cited by 14 publications

(25 citation statements)

References 19 publications

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“…In our early experiments we noted the optimal effect of the two oppositely charged polypeptides α-poly-L-lysine and poly-Lglutamate, which creates a matrix that serves as a mechanical barrier for adhesion formation [16]. Previous studies have also shown no effect on local immunological functions, i.e.…”

Section: Discussionmentioning

confidence: 92%

“…Previous studies have also shown no effect on local immunological functions, i.e. peritoneal macrophages, and a local clearance of this biodegradable matrix within 4 weeks [16,19]. 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.…”

Section: Discussionmentioning

confidence: 99%

“…In previous experimental studies we have shown the strong postsurgical intraabdominal anti-adhesive effect of differently charged polypeptides [16]. In our early experiments we noted the optimal effect of the two oppositely charged polypeptides α-poly-L-lysine and poly-Lglutamate, which creates a matrix that serves as a mechanical barrier for adhesion formation [16].…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Isaksson¹,

Åkerberg²,

Said³

et al. 2011

JBiSE

Self Cite

View full text Add to dashboard Cite

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Anti‐adhesive effect of chondrocyte‐derived extracellular matrix surface‐modified with poly‐L‐lysine

Song

Park

et al. 2021

J Tissue Eng Regen Med

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After an injury, soft tissue structures in the body undergo a natural healing process through specific phases of healing. Adhesions occur as abnormal attachments between tissues and organs through the formation of blood vessels and/or fibrinous adhesions during the regenerative repair process. In this study, we developed an adhesion-preventing membrane with an improved physical protection function by modifying the surface of chondrocyte-derived extracellular matrices (CECM) with anti-adhesion function. We attempted to change the negative charge of the CECM surface to neutral using poly-L-lysine (PLL) and investigated whether it blocked fibroblast adhesion to it and showed an improved anti-adhesion effect in animal models of tissue adhesion. The surface of the membrane was modified with PLL coating (PLL 10), which neutralized the surface charge. We confirmed that the surface characteristics except for the potential difference were maintained after the modification and tested cell attachment in vitro. Adhesion inhibition was identified in a peritoneal adhesion animal model at 1 week and in a subcutaneous adhesion model for 4 weeks. Neutralized CECM (N-CECM) suppressed fibroblast and endothelial cell adhesion in vitro and inhibited abdominal adhesions in vivo. The CECM appeared to actively inhibit the infiltration of endothelial cells into the injured site, thereby suppressing adhesion formation, which differed from conventional adhesion barriers in the mode of action. Furthermore, the N-CECM remained intact without degradation for more than 4 weeks in vivo and exerted anti-adhesion effects for a long time. This study demonstrated that PLL10 surface modification rendered a neutral charge to the polymer on the extracellular matrix surface, thereby inhibiting cell and tissue adhesion. Furthermore, this study suggests a means to modify extracellular matrix surfaces to meet the specific requirements of the target tissue in preventing post-surgical adhesions.

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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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Novel treatment in peritoneal adhesion prevention: Protection by polypeptides

Abstract: The intraperitoneal administration of poly-L-lysine and poly-L-glutamate resulted in a significant decrease in experimental postoperative peritoneal adhesions.

Cited by 14 publications

References 19 publications

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

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

Anti‐adhesive effect of chondrocyte‐derived extracellular matrix surface‐modified with poly‐L‐lysine

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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