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Cardiotoxicity of Chemical Substances: An Emerging Hazard Class

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating subs...

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Autores principales: Georgiadis, Nikolaos, Tsarouhas, Konstantinos, Dorne, Jean-Lou C. M., Kass, George E. N., Laspa, Petroula, Toutouzas, Konstantinos, Koulaouzidou, Elisabeth A., Kouretas, Dimitrios, Tsitsimpikou, Christina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316944/
https://www.ncbi.nlm.nih.gov/pubmed/35877588
http://dx.doi.org/10.3390/jcdd9070226
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author Georgiadis, Nikolaos
Tsarouhas, Konstantinos
Dorne, Jean-Lou C. M.
Kass, George E. N.
Laspa, Petroula
Toutouzas, Konstantinos
Koulaouzidou, Elisabeth A.
Kouretas, Dimitrios
Tsitsimpikou, Christina
author_facet Georgiadis, Nikolaos
Tsarouhas, Konstantinos
Dorne, Jean-Lou C. M.
Kass, George E. N.
Laspa, Petroula
Toutouzas, Konstantinos
Koulaouzidou, Elisabeth A.
Kouretas, Dimitrios
Tsitsimpikou, Christina
author_sort Georgiadis, Nikolaos
collection PubMed
description (1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.
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spelling pubmed-93169442022-07-27 Cardiotoxicity of Chemical Substances: An Emerging Hazard Class Georgiadis, Nikolaos Tsarouhas, Konstantinos Dorne, Jean-Lou C. M. Kass, George E. N. Laspa, Petroula Toutouzas, Konstantinos Koulaouzidou, Elisabeth A. Kouretas, Dimitrios Tsitsimpikou, Christina J Cardiovasc Dev Dis Review (1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria. MDPI 2022-07-14 /pmc/articles/PMC9316944/ /pubmed/35877588 http://dx.doi.org/10.3390/jcdd9070226 Text en © 2022 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 Review
Georgiadis, Nikolaos
Tsarouhas, Konstantinos
Dorne, Jean-Lou C. M.
Kass, George E. N.
Laspa, Petroula
Toutouzas, Konstantinos
Koulaouzidou, Elisabeth A.
Kouretas, Dimitrios
Tsitsimpikou, Christina
Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title_full Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title_fullStr Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title_full_unstemmed Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title_short Cardiotoxicity of Chemical Substances: An Emerging Hazard Class
title_sort cardiotoxicity of chemical substances: an emerging hazard class
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316944/
https://www.ncbi.nlm.nih.gov/pubmed/35877588
http://dx.doi.org/10.3390/jcdd9070226
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