Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice

Autores
Pistell, Paul J.; Gupta, Sunita; Knight, Alecia G.; Domingue, Michelle; Uranga, Romina Maria; Ingram, Donald K.; Kheterpal, Indu; Ruiz, Carmen; Keller, Jeffrey N.; Bruce Keller, Annadora J.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It is well established that HIV antiretroviral drugs, particularly protease inhibitors, frequently elicit a metabolic syndrome that may include hyperlipidemia, lipodystrophy, and insulin resistance. Metabolic dysfunction in non-HIV-infected subjects has been repeatedly associated with cognitive impairment in epidemiological and experimental studies, but it is not yet understood if antiretroviral therapy-induced metabolic syndrome might contribute to HIV-associated neurologic decline. To determine if protease inhibitor-induced metabolic dysfunction in mice is accompanied by adverse neurologic effects, C57BL/6 mice were given combined lopinavir/ritonavir (50/12.5 to 200/50 mg/kg) daily for 3 weeks. Data show that lopinavir/ritonavir administration caused significant metabolic derangement, including alterations in body weight and fat mass, as well as dose-dependent patterns of hyperlipidemia, hypoadiponectinemia, hypoleptinemia, and hyperinsulinemia. Evaluation of neurologic function revealed that even the lowest dose of lopinavir/ritonavir caused significant cognitive impairment assessed in multi-unit T-maze, but did not affect motoric functions assessed as rotarod performance. Collectively, our results indicate that repeated lopinavir/ritonavir administration produces cognitive as well as metabolic impairments, and suggest that the development of selective aspects of metabolic syndrome in HIV patients could contribute to HIV-associated neurocognitive disorders.
Fil: Pistell, Paul J.. Louisiana State University System,; Estados Unidos
Fil: Gupta, Sunita. Louisiana State University System,; Estados Unidos
Fil: Knight, Alecia G.. Louisiana State University System,; Estados Unidos
Fil: Domingue, Michelle. Louisiana State University System,; Estados Unidos
Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Ingram, Donald K.. Louisiana State University System,; Estados Unidos
Fil: Kheterpal, Indu. Louisiana State University System,; Estados Unidos
Fil: Ruiz, Carmen. Louisiana State University System,; Estados Unidos
Fil: Keller, Jeffrey N.. Louisiana State University System,; Estados Unidos
Fil: Bruce Keller, Annadora J.. Louisiana State University System,; Estados Unidos
Materia
HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS
HIV PROTEASE INHIBITORS
HYPERTRIGLYCERIDEMIA
METABOLIC SYNDROME
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:11336/43268
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/43268
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 micePistell, Paul J.Gupta, SunitaKnight, Alecia G.Domingue, MichelleUranga, Romina MariaIngram, Donald K.Kheterpal, InduRuiz, CarmenKeller, Jeffrey N.Bruce Keller, Annadora J.HIV-ASSOCIATED NEUROCOGNITIVE DISORDERSHIV PROTEASE INHIBITORSHYPERTRIGLYCERIDEMIAMETABOLIC SYNDROMEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It is well established that HIV antiretroviral drugs, particularly protease inhibitors, frequently elicit a metabolic syndrome that may include hyperlipidemia, lipodystrophy, and insulin resistance. Metabolic dysfunction in non-HIV-infected subjects has been repeatedly associated with cognitive impairment in epidemiological and experimental studies, but it is not yet understood if antiretroviral therapy-induced metabolic syndrome might contribute to HIV-associated neurologic decline. To determine if protease inhibitor-induced metabolic dysfunction in mice is accompanied by adverse neurologic effects, C57BL/6 mice were given combined lopinavir/ritonavir (50/12.5 to 200/50 mg/kg) daily for 3 weeks. Data show that lopinavir/ritonavir administration caused significant metabolic derangement, including alterations in body weight and fat mass, as well as dose-dependent patterns of hyperlipidemia, hypoadiponectinemia, hypoleptinemia, and hyperinsulinemia. Evaluation of neurologic function revealed that even the lowest dose of lopinavir/ritonavir caused significant cognitive impairment assessed in multi-unit T-maze, but did not affect motoric functions assessed as rotarod performance. Collectively, our results indicate that repeated lopinavir/ritonavir administration produces cognitive as well as metabolic impairments, and suggest that the development of selective aspects of metabolic syndrome in HIV patients could contribute to HIV-associated neurocognitive disorders.Fil: Pistell, Paul J.. Louisiana State University System,; Estados UnidosFil: Gupta, Sunita. Louisiana State University System,; Estados UnidosFil: Knight, Alecia G.. Louisiana State University System,; Estados UnidosFil: Domingue, Michelle. Louisiana State University System,; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Ingram, Donald K.. Louisiana State University System,; Estados UnidosFil: Kheterpal, Indu. Louisiana State University System,; Estados UnidosFil: Ruiz, Carmen. Louisiana State University System,; Estados UnidosFil: Keller, Jeffrey N.. Louisiana State University System,; Estados UnidosFil: Bruce Keller, Annadora J.. Louisiana State University System,; Estados UnidosElsevier Science2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43268Pistell, Paul J.; Gupta, Sunita; Knight, Alecia G.; Domingue, Michelle; Uranga, Romina Maria; et al.; Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice; Elsevier Science; Antiviral Research; 88; 3; 12-2010; 334-3420166-3542CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991583/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2010.10.006info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166354210007679info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:57:59Zoai:ri.conicet.gov.ar:11336/43268instacron: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:34982026-08-25 14:58:00.426CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
title Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
spellingShingle Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
Pistell, Paul J.
HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS
HIV PROTEASE INHIBITORS
HYPERTRIGLYCERIDEMIA
METABOLIC SYNDROME
title_short Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
title_full Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
title_fullStr Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
title_full_unstemmed Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
title_sort Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
dc.creator.none.fl_str_mv Pistell, Paul J.
Gupta, Sunita
Knight, Alecia G.
Domingue, Michelle
Uranga, Romina Maria
Ingram, Donald K.
Kheterpal, Indu
Ruiz, Carmen
Keller, Jeffrey N.
Bruce Keller, Annadora J.
author Pistell, Paul J.
author_facet Pistell, Paul J.
Gupta, Sunita
Knight, Alecia G.
Domingue, Michelle
Uranga, Romina Maria
Ingram, Donald K.
Kheterpal, Indu
Ruiz, Carmen
Keller, Jeffrey N.
Bruce Keller, Annadora J.
author_role author
author2 Gupta, Sunita
Knight, Alecia G.
Domingue, Michelle
Uranga, Romina Maria
Ingram, Donald K.
Kheterpal, Indu
Ruiz, Carmen
Keller, Jeffrey N.
Bruce Keller, Annadora J.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS
HIV PROTEASE INHIBITORS
HYPERTRIGLYCERIDEMIA
METABOLIC SYNDROME
topic HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS
HIV PROTEASE INHIBITORS
HYPERTRIGLYCERIDEMIA
METABOLIC SYNDROME
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv It is well established that HIV antiretroviral drugs, particularly protease inhibitors, frequently elicit a metabolic syndrome that may include hyperlipidemia, lipodystrophy, and insulin resistance. Metabolic dysfunction in non-HIV-infected subjects has been repeatedly associated with cognitive impairment in epidemiological and experimental studies, but it is not yet understood if antiretroviral therapy-induced metabolic syndrome might contribute to HIV-associated neurologic decline. To determine if protease inhibitor-induced metabolic dysfunction in mice is accompanied by adverse neurologic effects, C57BL/6 mice were given combined lopinavir/ritonavir (50/12.5 to 200/50 mg/kg) daily for 3 weeks. Data show that lopinavir/ritonavir administration caused significant metabolic derangement, including alterations in body weight and fat mass, as well as dose-dependent patterns of hyperlipidemia, hypoadiponectinemia, hypoleptinemia, and hyperinsulinemia. Evaluation of neurologic function revealed that even the lowest dose of lopinavir/ritonavir caused significant cognitive impairment assessed in multi-unit T-maze, but did not affect motoric functions assessed as rotarod performance. Collectively, our results indicate that repeated lopinavir/ritonavir administration produces cognitive as well as metabolic impairments, and suggest that the development of selective aspects of metabolic syndrome in HIV patients could contribute to HIV-associated neurocognitive disorders.
Fil: Pistell, Paul J.. Louisiana State University System,; Estados Unidos
Fil: Gupta, Sunita. Louisiana State University System,; Estados Unidos
Fil: Knight, Alecia G.. Louisiana State University System,; Estados Unidos
Fil: Domingue, Michelle. Louisiana State University System,; Estados Unidos
Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Ingram, Donald K.. Louisiana State University System,; Estados Unidos
Fil: Kheterpal, Indu. Louisiana State University System,; Estados Unidos
Fil: Ruiz, Carmen. Louisiana State University System,; Estados Unidos
Fil: Keller, Jeffrey N.. Louisiana State University System,; Estados Unidos
Fil: Bruce Keller, Annadora J.. Louisiana State University System,; Estados Unidos
description It is well established that HIV antiretroviral drugs, particularly protease inhibitors, frequently elicit a metabolic syndrome that may include hyperlipidemia, lipodystrophy, and insulin resistance. Metabolic dysfunction in non-HIV-infected subjects has been repeatedly associated with cognitive impairment in epidemiological and experimental studies, but it is not yet understood if antiretroviral therapy-induced metabolic syndrome might contribute to HIV-associated neurologic decline. To determine if protease inhibitor-induced metabolic dysfunction in mice is accompanied by adverse neurologic effects, C57BL/6 mice were given combined lopinavir/ritonavir (50/12.5 to 200/50 mg/kg) daily for 3 weeks. Data show that lopinavir/ritonavir administration caused significant metabolic derangement, including alterations in body weight and fat mass, as well as dose-dependent patterns of hyperlipidemia, hypoadiponectinemia, hypoleptinemia, and hyperinsulinemia. Evaluation of neurologic function revealed that even the lowest dose of lopinavir/ritonavir caused significant cognitive impairment assessed in multi-unit T-maze, but did not affect motoric functions assessed as rotarod performance. Collectively, our results indicate that repeated lopinavir/ritonavir administration produces cognitive as well as metabolic impairments, and suggest that the development of selective aspects of metabolic syndrome in HIV patients could contribute to HIV-associated neurocognitive disorders.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
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/11336/43268
Pistell, Paul J.; Gupta, Sunita; Knight, Alecia G.; Domingue, Michelle; Uranga, Romina Maria; et al.; Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice; Elsevier Science; Antiviral Research; 88; 3; 12-2010; 334-342
0166-3542
CONICET Digital
CONICET
url http://hdl.handle.net/11336/43268
identifier_str_mv Pistell, Paul J.; Gupta, Sunita; Knight, Alecia G.; Domingue, Michelle; Uranga, Romina Maria; et al.; Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice; Elsevier Science; Antiviral Research; 88; 3; 12-2010; 334-342
0166-3542
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.ncbi.nlm.nih.gov/pmc/articles/PMC2991583/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2010.10.006
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0166354210007679
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
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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score 13.334379

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