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A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis
The toxicity of in vitro tested compounds is usually evaluated based on AC(50) values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC(50). In the present study, 22 pol...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491109/ https://www.ncbi.nlm.nih.gov/pubmed/28662177 http://dx.doi.org/10.1371/journal.pone.0180022 |
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author | Boncler, Magdalena Golanski, Jacek Lukasiak, Magdalena Redzynia, Malgorzata Dastych, Jaroslaw Watala, Cezary |
author_facet | Boncler, Magdalena Golanski, Jacek Lukasiak, Magdalena Redzynia, Malgorzata Dastych, Jaroslaw Watala, Cezary |
author_sort | Boncler, Magdalena |
collection | PubMed |
description | The toxicity of in vitro tested compounds is usually evaluated based on AC(50) values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC(50). In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action. |
format | Online Article Text |
id | pubmed-5491109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54911092017-07-18 A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis Boncler, Magdalena Golanski, Jacek Lukasiak, Magdalena Redzynia, Malgorzata Dastych, Jaroslaw Watala, Cezary PLoS One Research Article The toxicity of in vitro tested compounds is usually evaluated based on AC(50) values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC(50). In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action. Public Library of Science 2017-06-29 /pmc/articles/PMC5491109/ /pubmed/28662177 http://dx.doi.org/10.1371/journal.pone.0180022 Text en © 2017 Boncler et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Boncler, Magdalena Golanski, Jacek Lukasiak, Magdalena Redzynia, Malgorzata Dastych, Jaroslaw Watala, Cezary A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title | A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title_full | A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title_fullStr | A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title_full_unstemmed | A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title_short | A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
title_sort | new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491109/ https://www.ncbi.nlm.nih.gov/pubmed/28662177 http://dx.doi.org/10.1371/journal.pone.0180022 |
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