Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses

Autores
Hernando, Marcelo Pablo; Cogo Pagella, Joaquín; de la Rosa, Florencia Grisel; Giannuzzi, Leda; Cervino, Claudio
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cyanotoxins are a significant concern due to their frequent presence in Southamerica waters. While numerous studies have investigated the toxic effects of MC-LR, knowledge regarding the toxicity of [D-Leu1]MC-LR remains limited. The aim of this study was to determine the impact of [D-Leu1]MC-LR and MC-LR administration on different brain structures in rats and the resulting modifications in oxidative stress. Male Sprague-Dawley rats were divided into two groups and administered 5 intraperitoneal injections of mixed MCs at doses of 2 and 15 μg kg1 for each injection over a 21-day period, i.e. total doses of 10 and 75 μg kg1.The MCs consisted on MC-LR (3 %), [D-Leu1]MC-LR (96.7 %) and others (0.3 %) isoforms. To evaluate the effect of treatments with different doses, the concentration of both MC isoforms, reactive oxygen species (ROS), lipid damage and antioxidant activity were measured in the cerebral cortex, hippocampus, striatum and cerebellum. The results revealed variability in MC concentration across brain regions. The accumulation rate of MC-LR was 2000 times higher than that of [D-Leu1]MC-LR, regardless of the dose administered at different areas. Taken together, our results highlighted that chronic exposure to MCs induced a mild oxidative stress in the rat brain characterized by increased ROS and antioxidant defense activation due to [D-Leu1]MC-LR in both the striatum and cortex at high dose. At low dose, the uptake of only MC-LR was determined in the cerebellum and hippocampus, resulting in increased ROS levels but no change in CAT activity in the hippocampus. In contrast, in the cerebellum, there was a decrease in ROS, possibly due to increased CAT consumption. However, the absence of detection of an MC variant under certain conditions does not allow for the exclusion of its metabolic effects. Chronic MC administration resulted in dose- and region-dependent distribution within the rat brain. Reactive species levels and cellular responses also varied by dose and region.
Fil: Hernando, Marcelo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Morón; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Cogo Pagella, Joaquín. Universidad de Morón; Argentina
Fil: de la Rosa, Florencia Grisel. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Giannuzzi, Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cervino, Claudio. Universidad de Morón; Argentina
Materia
Microcystin
rat brain
oxidative stress
antioxidant capacity
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:11336/265621
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/265621
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responsesHernando, Marcelo PabloCogo Pagella, Joaquínde la Rosa, Florencia GriselGiannuzzi, LedaCervino, ClaudioMicrocystinrat brainoxidative stressantioxidant capacityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cyanotoxins are a significant concern due to their frequent presence in Southamerica waters. While numerous studies have investigated the toxic effects of MC-LR, knowledge regarding the toxicity of [D-Leu1]MC-LR remains limited. The aim of this study was to determine the impact of [D-Leu1]MC-LR and MC-LR administration on different brain structures in rats and the resulting modifications in oxidative stress. Male Sprague-Dawley rats were divided into two groups and administered 5 intraperitoneal injections of mixed MCs at doses of 2 and 15 μg kg1 for each injection over a 21-day period, i.e. total doses of 10 and 75 μg kg1.The MCs consisted on MC-LR (3 %), [D-Leu1]MC-LR (96.7 %) and others (0.3 %) isoforms. To evaluate the effect of treatments with different doses, the concentration of both MC isoforms, reactive oxygen species (ROS), lipid damage and antioxidant activity were measured in the cerebral cortex, hippocampus, striatum and cerebellum. The results revealed variability in MC concentration across brain regions. The accumulation rate of MC-LR was 2000 times higher than that of [D-Leu1]MC-LR, regardless of the dose administered at different areas. Taken together, our results highlighted that chronic exposure to MCs induced a mild oxidative stress in the rat brain characterized by increased ROS and antioxidant defense activation due to [D-Leu1]MC-LR in both the striatum and cortex at high dose. At low dose, the uptake of only MC-LR was determined in the cerebellum and hippocampus, resulting in increased ROS levels but no change in CAT activity in the hippocampus. In contrast, in the cerebellum, there was a decrease in ROS, possibly due to increased CAT consumption. However, the absence of detection of an MC variant under certain conditions does not allow for the exclusion of its metabolic effects. Chronic MC administration resulted in dose- and region-dependent distribution within the rat brain. Reactive species levels and cellular responses also varied by dose and region.Fil: Hernando, Marcelo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Morón; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Cogo Pagella, Joaquín. Universidad de Morón; ArgentinaFil: de la Rosa, Florencia Grisel. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Giannuzzi, Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cervino, Claudio. Universidad de Morón; ArgentinaElsevier2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265621Hernando, Marcelo Pablo; Cogo Pagella, Joaquín; de la Rosa, Florencia Grisel; Giannuzzi, Leda; Cervino, Claudio; Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses; Elsevier; Current Research in Microbial Sciences; 8; 5-2025; 1-102666-5174CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S266651742500063Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.crmicr.2025.100401info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:59:27Zoai:ri.conicet.gov.ar:11336/265621instacron: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:34982025-09-17 10:59:27.337CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
title Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
spellingShingle Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
Hernando, Marcelo Pablo
Microcystin
rat brain
oxidative stress
antioxidant capacity
title_short Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
title_full Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
title_fullStr Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
title_full_unstemmed Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
title_sort Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses
dc.creator.none.fl_str_mv Hernando, Marcelo Pablo
Cogo Pagella, Joaquín
de la Rosa, Florencia Grisel
Giannuzzi, Leda
Cervino, Claudio
author Hernando, Marcelo Pablo
author_facet Hernando, Marcelo Pablo
Cogo Pagella, Joaquín
de la Rosa, Florencia Grisel
Giannuzzi, Leda
Cervino, Claudio
author_role author
author2 Cogo Pagella, Joaquín
de la Rosa, Florencia Grisel
Giannuzzi, Leda
Cervino, Claudio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Microcystin
rat brain
oxidative stress
antioxidant capacity
topic Microcystin
rat brain
oxidative stress
antioxidant capacity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cyanotoxins are a significant concern due to their frequent presence in Southamerica waters. While numerous studies have investigated the toxic effects of MC-LR, knowledge regarding the toxicity of [D-Leu1]MC-LR remains limited. The aim of this study was to determine the impact of [D-Leu1]MC-LR and MC-LR administration on different brain structures in rats and the resulting modifications in oxidative stress. Male Sprague-Dawley rats were divided into two groups and administered 5 intraperitoneal injections of mixed MCs at doses of 2 and 15 μg kg1 for each injection over a 21-day period, i.e. total doses of 10 and 75 μg kg1.The MCs consisted on MC-LR (3 %), [D-Leu1]MC-LR (96.7 %) and others (0.3 %) isoforms. To evaluate the effect of treatments with different doses, the concentration of both MC isoforms, reactive oxygen species (ROS), lipid damage and antioxidant activity were measured in the cerebral cortex, hippocampus, striatum and cerebellum. The results revealed variability in MC concentration across brain regions. The accumulation rate of MC-LR was 2000 times higher than that of [D-Leu1]MC-LR, regardless of the dose administered at different areas. Taken together, our results highlighted that chronic exposure to MCs induced a mild oxidative stress in the rat brain characterized by increased ROS and antioxidant defense activation due to [D-Leu1]MC-LR in both the striatum and cortex at high dose. At low dose, the uptake of only MC-LR was determined in the cerebellum and hippocampus, resulting in increased ROS levels but no change in CAT activity in the hippocampus. In contrast, in the cerebellum, there was a decrease in ROS, possibly due to increased CAT consumption. However, the absence of detection of an MC variant under certain conditions does not allow for the exclusion of its metabolic effects. Chronic MC administration resulted in dose- and region-dependent distribution within the rat brain. Reactive species levels and cellular responses also varied by dose and region.
Fil: Hernando, Marcelo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Morón; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Cogo Pagella, Joaquín. Universidad de Morón; Argentina
Fil: de la Rosa, Florencia Grisel. Universidad de Morón; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Giannuzzi, Leda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cervino, Claudio. Universidad de Morón; Argentina
description Cyanotoxins are a significant concern due to their frequent presence in Southamerica waters. While numerous studies have investigated the toxic effects of MC-LR, knowledge regarding the toxicity of [D-Leu1]MC-LR remains limited. The aim of this study was to determine the impact of [D-Leu1]MC-LR and MC-LR administration on different brain structures in rats and the resulting modifications in oxidative stress. Male Sprague-Dawley rats were divided into two groups and administered 5 intraperitoneal injections of mixed MCs at doses of 2 and 15 μg kg1 for each injection over a 21-day period, i.e. total doses of 10 and 75 μg kg1.The MCs consisted on MC-LR (3 %), [D-Leu1]MC-LR (96.7 %) and others (0.3 %) isoforms. To evaluate the effect of treatments with different doses, the concentration of both MC isoforms, reactive oxygen species (ROS), lipid damage and antioxidant activity were measured in the cerebral cortex, hippocampus, striatum and cerebellum. The results revealed variability in MC concentration across brain regions. The accumulation rate of MC-LR was 2000 times higher than that of [D-Leu1]MC-LR, regardless of the dose administered at different areas. Taken together, our results highlighted that chronic exposure to MCs induced a mild oxidative stress in the rat brain characterized by increased ROS and antioxidant defense activation due to [D-Leu1]MC-LR in both the striatum and cortex at high dose. At low dose, the uptake of only MC-LR was determined in the cerebellum and hippocampus, resulting in increased ROS levels but no change in CAT activity in the hippocampus. In contrast, in the cerebellum, there was a decrease in ROS, possibly due to increased CAT consumption. However, the absence of detection of an MC variant under certain conditions does not allow for the exclusion of its metabolic effects. Chronic MC administration resulted in dose- and region-dependent distribution within the rat brain. Reactive species levels and cellular responses also varied by dose and region.
publishDate 2025
dc.date.none.fl_str_mv 2025-05
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/11336/265621
Hernando, Marcelo Pablo; Cogo Pagella, Joaquín; de la Rosa, Florencia Grisel; Giannuzzi, Leda; Cervino, Claudio; Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses; Elsevier; Current Research in Microbial Sciences; 8; 5-2025; 1-10
2666-5174
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265621
identifier_str_mv Hernando, Marcelo Pablo; Cogo Pagella, Joaquín; de la Rosa, Florencia Grisel; Giannuzzi, Leda; Cervino, Claudio; Differential impact of microcystins MC-LR and [D-Leu1]MC-LR in different areas of the rat brain after chronic exposure: oxidative stress and antioxidant responses; Elsevier; Current Research in Microbial Sciences; 8; 5-2025; 1-10
2666-5174
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://linkinghub.elsevier.com/retrieve/pii/S266651742500063X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.crmicr.2025.100401
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
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.001348

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