Cargando…
Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity
Consumers are exposed to thousands of chemicals with potentially adverse health effects. However, these chemicals will never be tested for toxicity because of the immense resources needed for animal-based (in vivo) toxicological studies. Today, there are no viable in vitro alternatives to these type...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901980/ https://www.ncbi.nlm.nih.gov/pubmed/31850077 http://dx.doi.org/10.3389/fgene.2019.01233 |
_version_ | 1783477597663920128 |
---|---|
author | Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders |
author_facet | Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders |
author_sort | Schyman, Patric |
collection | PubMed |
description | Consumers are exposed to thousands of chemicals with potentially adverse health effects. However, these chemicals will never be tested for toxicity because of the immense resources needed for animal-based (in vivo) toxicological studies. Today, there are no viable in vitro alternatives to these types of animal studies. To develop an in vitro approach, we investigated whether we could predict in vivo organ injuries in rats with the use of RNA-seq data acquired from tissues early in the development of toxicant-induced injury, by comparing gene expression data from RNA isolated from these rat tissues with those obtained from in vitro exposure of primary liver and kidney cells. We collected RNA-seq data from the liver and kidney tissues of Sprague-Dawley rats 8 or 24 h after exposing them to vehicle (control), low (25 mg/kg), or high (100 mg/kg) doses of thioacetamide, a known liver toxicant that promotes fibrosis; we used these doses and exposure times to cause only mild toxicant-induced injury. For the in vitro study, we treated two cell types from Sprague-Dawley rats, primary hepatocytes (vehicle; low, 0.025 mM; or high, 0.125 mM dose), and renal tube epithelial cells (vehicle; low, 0.125 mM; or high, 0.500 mM) dose) with the thioacetamide metabolite, thioacetamide-S-oxide, selecting in vitro doses and exposure times to recreate the early-stage toxicant-induced injury model that we achieved in vivo. RNA-seq data were collected 9 or 24 h after application of vehicle or thioacetamide-S-oxide. We found that our modular approach for the analysis of gene expression data derived from in vivo RNA-seq strongly correlated (R(2) > 0.6) with the in vitro results at two different dose levels of thioacetamide/thioacetamide-S-oxide after 24 h of exposure. The top-ranked liver injury modules in vitro correctly identified the ensuing development of liver fibrosis. |
format | Online Article Text |
id | pubmed-6901980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69019802019-12-17 Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders Front Genet Genetics Consumers are exposed to thousands of chemicals with potentially adverse health effects. However, these chemicals will never be tested for toxicity because of the immense resources needed for animal-based (in vivo) toxicological studies. Today, there are no viable in vitro alternatives to these types of animal studies. To develop an in vitro approach, we investigated whether we could predict in vivo organ injuries in rats with the use of RNA-seq data acquired from tissues early in the development of toxicant-induced injury, by comparing gene expression data from RNA isolated from these rat tissues with those obtained from in vitro exposure of primary liver and kidney cells. We collected RNA-seq data from the liver and kidney tissues of Sprague-Dawley rats 8 or 24 h after exposing them to vehicle (control), low (25 mg/kg), or high (100 mg/kg) doses of thioacetamide, a known liver toxicant that promotes fibrosis; we used these doses and exposure times to cause only mild toxicant-induced injury. For the in vitro study, we treated two cell types from Sprague-Dawley rats, primary hepatocytes (vehicle; low, 0.025 mM; or high, 0.125 mM dose), and renal tube epithelial cells (vehicle; low, 0.125 mM; or high, 0.500 mM) dose) with the thioacetamide metabolite, thioacetamide-S-oxide, selecting in vitro doses and exposure times to recreate the early-stage toxicant-induced injury model that we achieved in vivo. RNA-seq data were collected 9 or 24 h after application of vehicle or thioacetamide-S-oxide. We found that our modular approach for the analysis of gene expression data derived from in vivo RNA-seq strongly correlated (R(2) > 0.6) with the in vitro results at two different dose levels of thioacetamide/thioacetamide-S-oxide after 24 h of exposure. The top-ranked liver injury modules in vitro correctly identified the ensuing development of liver fibrosis. Frontiers Media S.A. 2019-11-26 /pmc/articles/PMC6901980/ /pubmed/31850077 http://dx.doi.org/10.3389/fgene.2019.01233 Text en Copyright © 2019 Schyman, Printz, Estes, O’Brien, Shiota and Wallqvist http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Schyman, Patric Printz, Richard L. Estes, Shanea K. O’Brien, Tracy P. Shiota, Masakazu Wallqvist, Anders Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title | Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title_full | Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title_fullStr | Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title_full_unstemmed | Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title_short | Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity |
title_sort | assessing chemical-induced liver injury in vivo from in vitro gene expression data in the rat: the case of thioacetamide toxicity |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901980/ https://www.ncbi.nlm.nih.gov/pubmed/31850077 http://dx.doi.org/10.3389/fgene.2019.01233 |
work_keys_str_mv | AT schymanpatric assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity AT printzrichardl assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity AT estesshaneak assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity AT obrientracyp assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity AT shiotamasakazu assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity AT wallqvistanders assessingchemicalinducedliverinjuryinvivofrominvitrogeneexpressiondataintheratthecaseofthioacetamidetoxicity |