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The effects of lipophilic substances on the shape of erythrocytes demonstrated by a new in vitro-method

Söderberg, Lars LU ; Haag, Linnea; Höglund, Peter LU ; Stenberg, Pål and Wahlgren, Marie LU (2009) In European Journal of Pharmaceutical Sciences 36(4-5). p.458-464
Abstract
Abstract



Low aqueous solubility of lipophilic agents, such as free fatty acids, hampers proper in vitro demonstration of biological effects, yielding an ambiguous in vitro-in vivo correlation. We have therefore developed a method for evaluating the acute effects of lipophilic substances on the shape of erythrocytes and estimated EC50 and Hill coefficient according to the sigmoidal Emax model.



The test substance dissolved in medium-chain triglyceride is coated on a polycarbonate slide which serves as a cover sheet of a Bürker chamber. Freshly collected finger-tip blood is diluted with autologous EDTA-plasma and introduced into the chamber. After ten min at 37 C, the cells are photographed under... (More)
Abstract



Low aqueous solubility of lipophilic agents, such as free fatty acids, hampers proper in vitro demonstration of biological effects, yielding an ambiguous in vitro-in vivo correlation. We have therefore developed a method for evaluating the acute effects of lipophilic substances on the shape of erythrocytes and estimated EC50 and Hill coefficient according to the sigmoidal Emax model.



The test substance dissolved in medium-chain triglyceride is coated on a polycarbonate slide which serves as a cover sheet of a Bürker chamber. Freshly collected finger-tip blood is diluted with autologous EDTA-plasma and introduced into the chamber. After ten min at 37 C, the cells are photographed under microscope and the fractions of normal and defect cells are evaluated. No staining is needed and the cells are kept viable during the test period.



With increasing chain length, fatty acids, aliphatic amines and alcohols all increased the fraction of defect erythrocytes in a concentration-dependent manner. The results indicate that several fatty acids are very potent in their acute actions on erythrocytes, and that this effect is due to chain length rather than conformation.



Conclusion: The technique offers a screening method for testing the harmful effects of small amounts of lipophilic substances on erythrocytes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmaceutical Sciences
volume
36
issue
4-5
pages
458 - 464
publisher
Elsevier
external identifiers
  • wos:000264008600010
  • scopus:59349090288
ISSN
1879-0720
DOI
10.1016/j.ejps.2008.11.011
language
English
LU publication?
yes
id
a881de00-56d1-43f8-81ef-21e79e958e10 (old id 1241394)
date added to LUP
2008-09-22 15:07:07
date last changed
2017-01-01 04:25:30
@article{a881de00-56d1-43f8-81ef-21e79e958e10,
  abstract     = {Abstract<br/><br>
<br/><br>
Low aqueous solubility of lipophilic agents, such as free fatty acids, hampers proper in vitro demonstration of biological effects, yielding an ambiguous in vitro-in vivo correlation. We have therefore developed a method for evaluating the acute effects of lipophilic substances on the shape of erythrocytes and estimated EC50 and Hill coefficient according to the sigmoidal Emax model. <br/><br>
<br/><br>
The test substance dissolved in medium-chain triglyceride is coated on a polycarbonate slide which serves as a cover sheet of a Bürker chamber. Freshly collected finger-tip blood is diluted with autologous EDTA-plasma and introduced into the chamber. After ten min at 37 C, the cells are photographed under microscope and the fractions of normal and defect cells are evaluated. No staining is needed and the cells are kept viable during the test period.<br/><br>
<br/><br>
With increasing chain length, fatty acids, aliphatic amines and alcohols all increased the fraction of defect erythrocytes in a concentration-dependent manner. The results indicate that several fatty acids are very potent in their acute actions on erythrocytes, and that this effect is due to chain length rather than conformation.<br/><br>
<br/><br>
Conclusion: The technique offers a screening method for testing the harmful effects of small amounts of lipophilic substances on erythrocytes.},
  author       = {Söderberg, Lars and Haag, Linnea and Höglund, Peter and Stenberg, Pål and Wahlgren, Marie},
  issn         = {1879-0720},
  language     = {eng},
  number       = {4-5},
  pages        = {458--464},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmaceutical Sciences},
  title        = {The effects of lipophilic substances on the shape of erythrocytes demonstrated by a new in vitro-method},
  url          = {http://dx.doi.org/10.1016/j.ejps.2008.11.011},
  volume       = {36},
  year         = {2009},
}