In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.
Isaksson, Karolin LU ; Åkerberg, Daniel LU ; Bauden, Monika LU
; Andersson, Roland
LU
and Tingstedt, Bobby
LU
(2014)
In Journal of Materials Science: Materials in Medicine
25(5).
p.1293-1299
- Abstract
- 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.... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4290901
- author
- Isaksson, Karolin
LU
; Åkerberg, Daniel
LU
; Bauden, Monika
LU
; Andersson, Roland
LU
and Tingstedt, Bobby
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Materials Science: Materials in Medicine
- volume
- 25
- issue
- 5
- pages
- 1293 - 1299
- publisher
- Springer
- external identifiers
-
- pmid:24449025
- wos:000334503300009
- scopus:84921930099
- pmid:24449025
- ISSN
- 1573-4838
- DOI
- 10.1007/s10856-014-5151-2
- language
- English
- LU publication?
- yes
- id
- 647721b4-3ac3-4e9e-be7b-0e7a146d33f8 (old id 4290901)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24449025?dopt=Abstract
- date added to LUP
- 2016-04-01 10:35:18
- date last changed
- 2022-02-10 03:35:37
@article{647721b4-3ac3-4e9e-be7b-0e7a146d33f8,
abstract = {{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.}},
author = {{Isaksson, Karolin and Åkerberg, Daniel and Bauden, Monika and Andersson, Roland and Tingstedt, Bobby}},
issn = {{1573-4838}},
language = {{eng}},
number = {{5}},
pages = {{1293--1299}},
publisher = {{Springer}},
series = {{Journal of Materials Science: Materials in Medicine}},
title = {{In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.}},
url = {{http://dx.doi.org/10.1007/s10856-014-5151-2}},
doi = {{10.1007/s10856-014-5151-2}},
volume = {{25}},
year = {{2014}},
}