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Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice

Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients’ quality of life. The aim of this study was to investigate the toxicity of...

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Autores principales: Lhuissier, Eva, Aury-Landas, Juliette, Bouet, Valentine, Bazille, Céline, Repesse, Yohann, Freret, Thomas, Boumédiene, Karim, Baugé, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945538/
https://www.ncbi.nlm.nih.gov/pubmed/29755682
http://dx.doi.org/10.18632/oncotarget.25062
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author Lhuissier, Eva
Aury-Landas, Juliette
Bouet, Valentine
Bazille, Céline
Repesse, Yohann
Freret, Thomas
Boumédiene, Karim
Baugé, Catherine
author_facet Lhuissier, Eva
Aury-Landas, Juliette
Bouet, Valentine
Bazille, Céline
Repesse, Yohann
Freret, Thomas
Boumédiene, Karim
Baugé, Catherine
author_sort Lhuissier, Eva
collection PubMed
description Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients’ quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known. Chronic injections of DZNep were performed intraperitoneally in male NMRI mice (2 mg/kg; i.p.; three times per week) during 8 weeks. A follow-up of body weight was assessed during all experiments. Histological analysis were performed on several organs. EZH2 expression and H3K27me3 were assayed by western-blot. Several behavioral tests were performed during treatment and 2 weeks after. A particular focus was made on spontaneous locomotor activity, cognitive functions (spontaneous alternation and recognition memory), and anxiety- and depression-related behavior. Hematological modifications were also assessed. Chronic DZNep treatment transiently reduced animal growth. It had no effect on most organs but provoked a reversible splenomegaly, and persistent testis reduction and erythropoiesis. DZNep administration did not alter animal behavior. In conclusion, this study is encouraging for the use of DZNep for cancer treatment. Indeed, it has no effect on animal behavior, conferring an advantageous safety, and induces irreversible side effects limited on testis which are unfortunately found in most chemotherapy treatments.
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spelling pubmed-59455382018-05-13 Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice Lhuissier, Eva Aury-Landas, Juliette Bouet, Valentine Bazille, Céline Repesse, Yohann Freret, Thomas Boumédiene, Karim Baugé, Catherine Oncotarget Research Paper Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients’ quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known. Chronic injections of DZNep were performed intraperitoneally in male NMRI mice (2 mg/kg; i.p.; three times per week) during 8 weeks. A follow-up of body weight was assessed during all experiments. Histological analysis were performed on several organs. EZH2 expression and H3K27me3 were assayed by western-blot. Several behavioral tests were performed during treatment and 2 weeks after. A particular focus was made on spontaneous locomotor activity, cognitive functions (spontaneous alternation and recognition memory), and anxiety- and depression-related behavior. Hematological modifications were also assessed. Chronic DZNep treatment transiently reduced animal growth. It had no effect on most organs but provoked a reversible splenomegaly, and persistent testis reduction and erythropoiesis. DZNep administration did not alter animal behavior. In conclusion, this study is encouraging for the use of DZNep for cancer treatment. Indeed, it has no effect on animal behavior, conferring an advantageous safety, and induces irreversible side effects limited on testis which are unfortunately found in most chemotherapy treatments. Impact Journals LLC 2018-04-17 /pmc/articles/PMC5945538/ /pubmed/29755682 http://dx.doi.org/10.18632/oncotarget.25062 Text en Copyright: © 2018 Lhuissier et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lhuissier, Eva
Aury-Landas, Juliette
Bouet, Valentine
Bazille, Céline
Repesse, Yohann
Freret, Thomas
Boumédiene, Karim
Baugé, Catherine
Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title_full Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title_fullStr Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title_full_unstemmed Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title_short Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice
title_sort evaluation of the impact of s-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin a, on tissue injury and cognitive function in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945538/
https://www.ncbi.nlm.nih.gov/pubmed/29755682
http://dx.doi.org/10.18632/oncotarget.25062
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