Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells

Autores
Chiappini, Florencia Ana; Alvarez, Laura; Lux, Victoria Adela R.; Randi, Andrea Silvana; Kleiman, Diana Leonor
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of humans to HCB produces a number of effects, such as triggering of porphyria, increased synthesis of liver microsomal enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats HCB induced hepatic porphyria, neurotoxic effects and toxic effects on the reproductive system, thyroid function and immune system. HCB is also known to cause tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3´,5,5´-tetraiodothyronine (T(4,) thyroxine) serum levels, without changes in TSH concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation evaluated by 5´-Br deoxiuridine (BrdU) incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in situ end-labeling of fragmented DNA, TUNEL, in rat thyroid glands. This process is associated with dose-dependent increases in cytochrome c release from the mitochondria and procaspase-9 processing to its active product. Caspase-8 was not activated. These studies indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the thyroid gland, involving the mitochondrial pathway.
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Hexachlorobenzene
Thyroid
Apoptosis
Mitochondria
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25060
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25060
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hexachlorobenzene triggers apoptosis in rat thyroid follicular cellsChiappini, Florencia AnaAlvarez, LauraLux, Victoria Adela R.Randi, Andrea SilvanaKleiman, Diana LeonorHexachlorobenzeneThyroidApoptosisMitochondriahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of humans to HCB produces a number of effects, such as triggering of porphyria, increased synthesis of liver microsomal enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats HCB induced hepatic porphyria, neurotoxic effects and toxic effects on the reproductive system, thyroid function and immune system. HCB is also known to cause tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3´,5,5´-tetraiodothyronine (T(4,) thyroxine) serum levels, without changes in TSH concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation evaluated by 5´-Br deoxiuridine (BrdU) incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in situ end-labeling of fragmented DNA, TUNEL, in rat thyroid glands. This process is associated with dose-dependent increases in cytochrome c release from the mitochondria and procaspase-9 processing to its active product. Caspase-8 was not activated. These studies indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the thyroid gland, involving the mitochondrial pathway.Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaOxford University Press2009-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25060Chiappini, Florencia Ana; Alvarez, Laura; Lux, Victoria Adela R.; Randi, Andrea Silvana; Kleiman, Diana Leonor; Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells; Oxford University Press; Toxicological Sciences; 108; 2; 4-2009; 301-3101096-60801096-0929CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article/108/2/301/1666219/Hexachlorobenzene-Triggers-Apoptosis-in-Ratinfo:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfp016info:eu-repo/semantics/altIdentifier/pmid/19182106info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:33Zoai:ri.conicet.gov.ar:11336/25060instacron: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:34982025-09-03 09:53:34.148CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
title Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
spellingShingle Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
Chiappini, Florencia Ana
Hexachlorobenzene
Thyroid
Apoptosis
Mitochondria
title_short Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
title_full Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
title_fullStr Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
title_full_unstemmed Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
title_sort Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells
dc.creator.none.fl_str_mv Chiappini, Florencia Ana
Alvarez, Laura
Lux, Victoria Adela R.
Randi, Andrea Silvana
Kleiman, Diana Leonor
author Chiappini, Florencia Ana
author_facet Chiappini, Florencia Ana
Alvarez, Laura
Lux, Victoria Adela R.
Randi, Andrea Silvana
Kleiman, Diana Leonor
author_role author
author2 Alvarez, Laura
Lux, Victoria Adela R.
Randi, Andrea Silvana
Kleiman, Diana Leonor
author2_role author
author
author
author
dc.subject.none.fl_str_mv Hexachlorobenzene
Thyroid
Apoptosis
Mitochondria
topic Hexachlorobenzene
Thyroid
Apoptosis
Mitochondria
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of humans to HCB produces a number of effects, such as triggering of porphyria, increased synthesis of liver microsomal enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats HCB induced hepatic porphyria, neurotoxic effects and toxic effects on the reproductive system, thyroid function and immune system. HCB is also known to cause tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3´,5,5´-tetraiodothyronine (T(4,) thyroxine) serum levels, without changes in TSH concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation evaluated by 5´-Br deoxiuridine (BrdU) incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in situ end-labeling of fragmented DNA, TUNEL, in rat thyroid glands. This process is associated with dose-dependent increases in cytochrome c release from the mitochondria and procaspase-9 processing to its active product. Caspase-8 was not activated. These studies indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the thyroid gland, involving the mitochondrial pathway.
Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of humans to HCB produces a number of effects, such as triggering of porphyria, increased synthesis of liver microsomal enzymes, neurological symptoms, immunological disorders and thyroid dysfunctions. In rats HCB induced hepatic porphyria, neurotoxic effects and toxic effects on the reproductive system, thyroid function and immune system. HCB is also known to cause tumors of the liver, thyroid and mammary gland in laboratory animals. The aim of this study was to investigate parameters of thyroid growth regulation, mainly cell proliferation and apoptosis in thyroid tissue from HCB (0.1, 1, 10, 100, and 500 mg/kg body weight)-treated female Wistar rats. The current study demonstrates that only the exposure to the highest HCB dose for 30 days, has adverse effects on thyroid endpoints examined related to thyroid gland morphology, and 3,3´,5,5´-tetraiodothyronine (T(4,) thyroxine) serum levels, without changes in TSH concentrations or in thyroid gland weight. Morphological changes, included flattened epithelium and increased colloid size compared with control tissue. Transforming growth factor (TGF-beta1) mRNA levels, evaluated by RT-PCR, revealed a significant upregulation after exposure to HCB (1, 10, 100 mg/kg body weight). Cell proliferation evaluated by 5´-Br deoxiuridine (BrdU) incorporation into DNA, was not altered at any dose. HCB (1, 10, 100 mg/kg body weight) induces apoptosis, evaluated by in situ end-labeling of fragmented DNA, TUNEL, in rat thyroid glands. This process is associated with dose-dependent increases in cytochrome c release from the mitochondria and procaspase-9 processing to its active product. Caspase-8 was not activated. These studies indicate that doses of HCB that do not disrupt thyroid economy induce TGF-beta1 expression and apoptosis in the thyroid gland, involving the mitochondrial pathway.
publishDate 2009
dc.date.none.fl_str_mv 2009-04
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/11336/25060
Chiappini, Florencia Ana; Alvarez, Laura; Lux, Victoria Adela R.; Randi, Andrea Silvana; Kleiman, Diana Leonor; Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells; Oxford University Press; Toxicological Sciences; 108; 2; 4-2009; 301-310
1096-6080
1096-0929
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25060
identifier_str_mv Chiappini, Florencia Ana; Alvarez, Laura; Lux, Victoria Adela R.; Randi, Andrea Silvana; Kleiman, Diana Leonor; Hexachlorobenzene triggers apoptosis in rat thyroid follicular cells; Oxford University Press; Toxicological Sciences; 108; 2; 4-2009; 301-310
1096-6080
1096-0929
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://academic.oup.com/toxsci/article/108/2/301/1666219/Hexachlorobenzene-Triggers-Apoptosis-in-Rat
info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfp016
info:eu-repo/semantics/altIdentifier/pmid/19182106
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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