Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to d...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Przemysław Sołek, Jennifer Mytych, Anna Tabęcka-Łonczyńska, Marek Koziorowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antidepressants apoptosis DNA methylation male fertility toxicity mechanisms Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e4019c0fb0ac4e8c8e88d7394c9f35d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e4019c0fb0ac4e8c8e88d7394c9f35d1
record_format	dspace
spelling	oai:doaj.org-article:e4019c0fb0ac4e8c8e88d7394c9f35d12021-11-11T17:16:52ZMolecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects10.3390/ijms2221118551422-00671661-6596https://doaj.org/article/e4019c0fb0ac4e8c8e88d7394c9f35d12021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11855https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.Przemysław SołekJennifer MytychAnna Tabęcka-ŁonczyńskaMarek KoziorowskiMDPI AGarticleantidepressantsapoptosisDNA methylationmale fertilitytoxicity mechanismsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11855, p 11855 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antidepressants apoptosis DNA methylation male fertility toxicity mechanisms Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	antidepressants apoptosis DNA methylation male fertility toxicity mechanisms Biology (General) QH301-705.5 Chemistry QD1-999 Przemysław Sołek Jennifer Mytych Anna Tabęcka-Łonczyńska Marek Koziorowski Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
description	The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.
format	article
author	Przemysław Sołek Jennifer Mytych Anna Tabęcka-Łonczyńska Marek Koziorowski
author_facet	Przemysław Sołek Jennifer Mytych Anna Tabęcka-Łonczyńska Marek Koziorowski
author_sort	Przemysław Sołek
title	Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
title_short	Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
title_full	Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
title_fullStr	Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
title_full_unstemmed	Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects
title_sort	molecular consequences of depression treatment: a potential in vitro mechanism for antidepressants-induced reprotoxic side effects
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e4019c0fb0ac4e8c8e88d7394c9f35d1
work_keys_str_mv	AT przemysławsołek molecularconsequencesofdepressiontreatmentapotentialinvitromechanismforantidepressantsinducedreprotoxicsideeffects AT jennifermytych molecularconsequencesofdepressiontreatmentapotentialinvitromechanismforantidepressantsinducedreprotoxicsideeffects AT annatabeckałonczynska molecularconsequencesofdepressiontreatmentapotentialinvitromechanismforantidepressantsinducedreprotoxicsideeffects AT marekkoziorowski molecularconsequencesofdepressiontreatmentapotentialinvitromechanismforantidepressantsinducedreprotoxicsideeffects
_version_	1718432150806593536

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

Ejemplares similares