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Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae

Chlorpromazine (CPZ) is still a commonly prescribed antipsychotic which causes poorly understood idiosyncratic toxicity such as cholestasis, phospholipidosis and steatosis. CPZ has diverse cellular targets and exerts various toxicity mechanisms whose exploration is necessary to understand CPZ side e...

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Autores principales: Muhieddine, Dina, Moughnié, Mohamad, Abdel-Razzak, Ziad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Slovak Toxicology Society SETOX 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061449/
https://www.ncbi.nlm.nih.gov/pubmed/32189986
http://dx.doi.org/10.2478/intox-2019-0006
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author Muhieddine, Dina
Moughnié, Mohamad
Abdel-Razzak, Ziad
author_facet Muhieddine, Dina
Moughnié, Mohamad
Abdel-Razzak, Ziad
author_sort Muhieddine, Dina
collection PubMed
description Chlorpromazine (CPZ) is still a commonly prescribed antipsychotic which causes poorly understood idiosyncratic toxicity such as cholestasis, phospholipidosis and steatosis. CPZ has diverse cellular targets and exerts various toxicity mechanisms whose exploration is necessary to understand CPZ side effects. We report here that CPZ causes a decrease of total lipid content in Saccharomyces cerevisiae at the same dose range as that used on mammalian cells. The observed lipid decrease was obvious after 4 and 9 hours of treatment, and disappeared after 24 hours due to cells adaptation to the chemical stress. The inhibitory effect of CPZ was antagonized by the antioxidant N-acetyl L-cysteine and is likely caused by the parent compound. The obtained results demonstrate that yeast model is valid to investigate the involved CPZ toxicity mechanisms, particularly in terms of lipids alteration. This would contribute to understand CPZ side effects in simple model and reduce experimentation on animals.
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spelling pubmed-70614492020-03-18 Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae Muhieddine, Dina Moughnié, Mohamad Abdel-Razzak, Ziad Interdiscip Toxicol Original Article Chlorpromazine (CPZ) is still a commonly prescribed antipsychotic which causes poorly understood idiosyncratic toxicity such as cholestasis, phospholipidosis and steatosis. CPZ has diverse cellular targets and exerts various toxicity mechanisms whose exploration is necessary to understand CPZ side effects. We report here that CPZ causes a decrease of total lipid content in Saccharomyces cerevisiae at the same dose range as that used on mammalian cells. The observed lipid decrease was obvious after 4 and 9 hours of treatment, and disappeared after 24 hours due to cells adaptation to the chemical stress. The inhibitory effect of CPZ was antagonized by the antioxidant N-acetyl L-cysteine and is likely caused by the parent compound. The obtained results demonstrate that yeast model is valid to investigate the involved CPZ toxicity mechanisms, particularly in terms of lipids alteration. This would contribute to understand CPZ side effects in simple model and reduce experimentation on animals. Slovak Toxicology Society SETOX 2019-09 2020-02-20 /pmc/articles/PMC7061449/ /pubmed/32189986 http://dx.doi.org/10.2478/intox-2019-0006 Text en Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc. https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. (CC BY-NC-ND 4.0)
spellingShingle Original Article
Muhieddine, Dina
Moughnié, Mohamad
Abdel-Razzak, Ziad
Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title_full Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title_fullStr Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title_full_unstemmed Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title_short Short communication: Chlorpromazine causes a time-dependent decrease of lipids in Saccharomyces cerevisiae
title_sort short communication: chlorpromazine causes a time-dependent decrease of lipids in saccharomyces cerevisiae
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061449/
https://www.ncbi.nlm.nih.gov/pubmed/32189986
http://dx.doi.org/10.2478/intox-2019-0006
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