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Potential and Limits of Kidney Cells for Evaluation of Renal Excretion

A large number of therapeutic drugs, herbal components and their metabolites are excreted by the kidneys. Therefore, generally applied models for estimating renal excretion, including freshly isolated rat proximal tubule cells, cultured tubule cells and immortalized kidney cell lines MDCKII, NRK-52E...

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Autores principales: Lechner, Christian, Mönning, Ursula, Reichel, Andreas, Fricker, Gert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464824/
https://www.ncbi.nlm.nih.gov/pubmed/34577608
http://dx.doi.org/10.3390/ph14090908
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author Lechner, Christian
Mönning, Ursula
Reichel, Andreas
Fricker, Gert
author_facet Lechner, Christian
Mönning, Ursula
Reichel, Andreas
Fricker, Gert
author_sort Lechner, Christian
collection PubMed
description A large number of therapeutic drugs, herbal components and their metabolites are excreted by the kidneys. Therefore, generally applied models for estimating renal excretion, including freshly isolated rat proximal tubule cells, cultured tubule cells and immortalized kidney cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1, were investigated regarding their predictive potential for active renal transport. Cultured proximal tubule cells showed an epithelial cell-like morphology and formed tight monolayers. However, mRNA expression analyses and immunohistochemical studies revealed patterns of tight junction proteins that were notably different from freshly isolated cells and distinct from those in vivo. High levels of mannitol permeation were found in NRK-52E, IHKE-1 and Caki-1 cells, suggesting that they are not suitable for bidirectional transport studies. Cultured cells and freshly isolated cells also differed in proximal tubule markers and transport proteins, indicating that cultured primary cells were in a state of dedifferentiation. Cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1 did not accurately reflect the characteristics of proximal tubules. The expression patterns of marker and transport proteins differed from freshly isolated primary cells. In summary, each of these models has profound disadvantages to consider when adopting them reliable models for the in vivo situation. Thus, they should not be used alone but only in combination.
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spelling pubmed-84648242021-09-27 Potential and Limits of Kidney Cells for Evaluation of Renal Excretion Lechner, Christian Mönning, Ursula Reichel, Andreas Fricker, Gert Pharmaceuticals (Basel) Article A large number of therapeutic drugs, herbal components and their metabolites are excreted by the kidneys. Therefore, generally applied models for estimating renal excretion, including freshly isolated rat proximal tubule cells, cultured tubule cells and immortalized kidney cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1, were investigated regarding their predictive potential for active renal transport. Cultured proximal tubule cells showed an epithelial cell-like morphology and formed tight monolayers. However, mRNA expression analyses and immunohistochemical studies revealed patterns of tight junction proteins that were notably different from freshly isolated cells and distinct from those in vivo. High levels of mannitol permeation were found in NRK-52E, IHKE-1 and Caki-1 cells, suggesting that they are not suitable for bidirectional transport studies. Cultured cells and freshly isolated cells also differed in proximal tubule markers and transport proteins, indicating that cultured primary cells were in a state of dedifferentiation. Cell lines MDCKII, NRK-52E, IHKE-1 and Caki-1 did not accurately reflect the characteristics of proximal tubules. The expression patterns of marker and transport proteins differed from freshly isolated primary cells. In summary, each of these models has profound disadvantages to consider when adopting them reliable models for the in vivo situation. Thus, they should not be used alone but only in combination. MDPI 2021-09-07 /pmc/articles/PMC8464824/ /pubmed/34577608 http://dx.doi.org/10.3390/ph14090908 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lechner, Christian
Mönning, Ursula
Reichel, Andreas
Fricker, Gert
Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title_full Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title_fullStr Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title_full_unstemmed Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title_short Potential and Limits of Kidney Cells for Evaluation of Renal Excretion
title_sort potential and limits of kidney cells for evaluation of renal excretion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464824/
https://www.ncbi.nlm.nih.gov/pubmed/34577608
http://dx.doi.org/10.3390/ph14090908
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