Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System

Autores
Sosa Alderete, Lucas Gastón; Vezza, Mariana Elisa; Ibañez, Sabrina Guadalupe; Schroeder, Peter; Agostini, Elizabeth; Talano, Melina Andrea
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L−1) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses.
Fil: Sosa Alderete, Lucas Gastón. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Vezza, Mariana Elisa. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Ibañez, Sabrina Guadalupe. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Schroeder, Peter. Helmholtz Zentrum München German Research Center for Environmental Health; Alemania
Fil: Agostini, Elizabeth. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Talano, Melina Andrea. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Materia
PARACETAMOL REMOVAL
GLUTATHIONE S-TRANSFERASES
HAIRY ROOTS CULTURES
CIRCADIAN CLOCK REGULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/273752
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/273752
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model SystemSosa Alderete, Lucas GastónVezza, Mariana ElisaIbañez, Sabrina GuadalupeSchroeder, PeterAgostini, ElizabethTalano, Melina AndreaPARACETAMOL REMOVALGLUTATHIONE S-TRANSFERASESHAIRY ROOTS CULTURESCIRCADIAN CLOCK REGULATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L−1) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses.Fil: Sosa Alderete, Lucas Gastón. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Vezza, Mariana Elisa. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Ibañez, Sabrina Guadalupe. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Schroeder, Peter. Helmholtz Zentrum München German Research Center for Environmental Health; AlemaniaFil: Agostini, Elizabeth. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Talano, Melina Andrea. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaMDPI2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/273752Sosa Alderete, Lucas Gastón; Vezza, Mariana Elisa; Ibañez, Sabrina Guadalupe; Schroeder, Peter; Agostini, Elizabeth; et al.; Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System; MDPI; Plants; 14; 17; 9-2025; 1-172223-7747CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2223-7747/14/17/2812info:eu-repo/semantics/altIdentifier/doi/10.3390/plants14172812info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:22:59Zoai:ri.conicet.gov.ar:11336/273752instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-05 10:22:59.653CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
title Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
spellingShingle Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
Sosa Alderete, Lucas Gastón
PARACETAMOL REMOVAL
GLUTATHIONE S-TRANSFERASES
HAIRY ROOTS CULTURES
CIRCADIAN CLOCK REGULATION
title_short Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
title_full Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
title_fullStr Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
title_full_unstemmed Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
title_sort Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System
dc.creator.none.fl_str_mv Sosa Alderete, Lucas Gastón
Vezza, Mariana Elisa
Ibañez, Sabrina Guadalupe
Schroeder, Peter
Agostini, Elizabeth
Talano, Melina Andrea
author Sosa Alderete, Lucas Gastón
author_facet Sosa Alderete, Lucas Gastón
Vezza, Mariana Elisa
Ibañez, Sabrina Guadalupe
Schroeder, Peter
Agostini, Elizabeth
Talano, Melina Andrea
author_role author
author2 Vezza, Mariana Elisa
Ibañez, Sabrina Guadalupe
Schroeder, Peter
Agostini, Elizabeth
Talano, Melina Andrea
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv PARACETAMOL REMOVAL
GLUTATHIONE S-TRANSFERASES
HAIRY ROOTS CULTURES
CIRCADIAN CLOCK REGULATION
topic PARACETAMOL REMOVAL
GLUTATHIONE S-TRANSFERASES
HAIRY ROOTS CULTURES
CIRCADIAN CLOCK REGULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L−1) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses.
Fil: Sosa Alderete, Lucas Gastón. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Vezza, Mariana Elisa. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Ibañez, Sabrina Guadalupe. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Schroeder, Peter. Helmholtz Zentrum München German Research Center for Environmental Health; Alemania
Fil: Agostini, Elizabeth. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Talano, Melina Andrea. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
description The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L−1) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/273752
Sosa Alderete, Lucas Gastón; Vezza, Mariana Elisa; Ibañez, Sabrina Guadalupe; Schroeder, Peter; Agostini, Elizabeth; et al.; Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System; MDPI; Plants; 14; 17; 9-2025; 1-17
2223-7747
CONICET Digital
CONICET
url http://hdl.handle.net/11336/273752
identifier_str_mv Sosa Alderete, Lucas Gastón; Vezza, Mariana Elisa; Ibañez, Sabrina Guadalupe; Schroeder, Peter; Agostini, Elizabeth; et al.; Unraveling Paracetamol Metabolism and Its Circadian Regulation: Insights from Tobacco Hairy Roots as a Model System; MDPI; Plants; 14; 17; 9-2025; 1-17
2223-7747
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2223-7747/14/17/2812
info:eu-repo/semantics/altIdentifier/doi/10.3390/plants14172812
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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