Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/15287394.2020.1805078 http://hdl.handle.net/11449/202023 |
Resumo: | Diazinon (DZN) is a broad-spectrum insecticide extensively used to control pests in crops and animals. Several investigators demonstrated that DZN produced tissue toxicity especially to the liver. In addition, the mitochondrion was implicated in DZN-induced toxicity, but the precise role of this organelle remains to be determined. The aim of this study was thus to examine the effects of DZN (50 to 150 μM) on the bioenergetics and mitochondrial permeability transition (MPT) associated processes in isolated rat liver mitochondria. DZN inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I, and succinate, substrate of complex II of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. MPT was estimated by the extent of mitochondrial swelling, in the presence of 10 µM Ca2+. DZN elicited MPT in a concentration-dependent manner, via a mechanism sensitive to cyclosporine A, EGTA, ruthenium red and N-ethylmaleimide, which was associated with mitochondrial Ca2+ efflux and cytochrome c release. DZN did not result in hydrogen peroxide accumulation or glutathione oxidation, but this insecticide oxidized endogenous NAD(P)H and protein thiol groups. Data suggest the involvement of mitochondria, via apoptosis, in the hepatic cytotoxicity attributed to DZN. |
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Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liverDiazinonlivermitochondrial membrane permeability transitionoxidative phosphorylationtoxicityDiazinon (DZN) is a broad-spectrum insecticide extensively used to control pests in crops and animals. Several investigators demonstrated that DZN produced tissue toxicity especially to the liver. In addition, the mitochondrion was implicated in DZN-induced toxicity, but the precise role of this organelle remains to be determined. The aim of this study was thus to examine the effects of DZN (50 to 150 μM) on the bioenergetics and mitochondrial permeability transition (MPT) associated processes in isolated rat liver mitochondria. DZN inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I, and succinate, substrate of complex II of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. MPT was estimated by the extent of mitochondrial swelling, in the presence of 10 µM Ca2+. DZN elicited MPT in a concentration-dependent manner, via a mechanism sensitive to cyclosporine A, EGTA, ruthenium red and N-ethylmaleimide, which was associated with mitochondrial Ca2+ efflux and cytochrome c release. DZN did not result in hydrogen peroxide accumulation or glutathione oxidation, but this insecticide oxidized endogenous NAD(P)H and protein thiol groups. Data suggest the involvement of mitochondria, via apoptosis, in the hepatic cytotoxicity attributed to DZN.Department of Animal Production College of Agricultural and Technological Sciences São Paulo State University (UnespDepartment of Animal Production College of Agricultural and Technological Sciences São Paulo State University (UnespUniversidade Estadual Paulista (Unesp)Miranda, Camila Araújo [UNESP]Guimarães, Anilda Rufino de Jesus Santos [UNESP]Bizerra, Paulo Francisco Veiga [UNESP]Mingatto, Fábio Erminio [UNESP]2020-12-12T02:47:51Z2020-12-12T02:47:51Z2020-09-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article616-629http://dx.doi.org/10.1080/15287394.2020.1805078Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 83, n. 17-18, p. 616-629, 2020.1087-26201528-7394http://hdl.handle.net/11449/20202310.1080/15287394.2020.18050782-s2.0-85089456708Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Toxicology and Environmental Health - Part A: Current Issuesinfo:eu-repo/semantics/openAccess2024-05-07T13:47:36Zoai:repositorio.unesp.br:11449/202023Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:16:37.021160Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
title |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
spellingShingle |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver Miranda, Camila Araújo [UNESP] Diazinon liver mitochondrial membrane permeability transition oxidative phosphorylation toxicity |
title_short |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
title_full |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
title_fullStr |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
title_full_unstemmed |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
title_sort |
Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver |
author |
Miranda, Camila Araújo [UNESP] |
author_facet |
Miranda, Camila Araújo [UNESP] Guimarães, Anilda Rufino de Jesus Santos [UNESP] Bizerra, Paulo Francisco Veiga [UNESP] Mingatto, Fábio Erminio [UNESP] |
author_role |
author |
author2 |
Guimarães, Anilda Rufino de Jesus Santos [UNESP] Bizerra, Paulo Francisco Veiga [UNESP] Mingatto, Fábio Erminio [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Miranda, Camila Araújo [UNESP] Guimarães, Anilda Rufino de Jesus Santos [UNESP] Bizerra, Paulo Francisco Veiga [UNESP] Mingatto, Fábio Erminio [UNESP] |
dc.subject.por.fl_str_mv |
Diazinon liver mitochondrial membrane permeability transition oxidative phosphorylation toxicity |
topic |
Diazinon liver mitochondrial membrane permeability transition oxidative phosphorylation toxicity |
description |
Diazinon (DZN) is a broad-spectrum insecticide extensively used to control pests in crops and animals. Several investigators demonstrated that DZN produced tissue toxicity especially to the liver. In addition, the mitochondrion was implicated in DZN-induced toxicity, but the precise role of this organelle remains to be determined. The aim of this study was thus to examine the effects of DZN (50 to 150 μM) on the bioenergetics and mitochondrial permeability transition (MPT) associated processes in isolated rat liver mitochondria. DZN inhibited state-3 respiration in mitochondria energized with glutamate plus malate, substrates of complex I, and succinate, substrate of complex II of the respiratory chain and decreased the mitochondrial membrane potential resulting in inhibition of ATP synthesis. MPT was estimated by the extent of mitochondrial swelling, in the presence of 10 µM Ca2+. DZN elicited MPT in a concentration-dependent manner, via a mechanism sensitive to cyclosporine A, EGTA, ruthenium red and N-ethylmaleimide, which was associated with mitochondrial Ca2+ efflux and cytochrome c release. DZN did not result in hydrogen peroxide accumulation or glutathione oxidation, but this insecticide oxidized endogenous NAD(P)H and protein thiol groups. Data suggest the involvement of mitochondria, via apoptosis, in the hepatic cytotoxicity attributed to DZN. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:47:51Z 2020-12-12T02:47:51Z 2020-09-16 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1080/15287394.2020.1805078 Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 83, n. 17-18, p. 616-629, 2020. 1087-2620 1528-7394 http://hdl.handle.net/11449/202023 10.1080/15287394.2020.1805078 2-s2.0-85089456708 |
url |
http://dx.doi.org/10.1080/15287394.2020.1805078 http://hdl.handle.net/11449/202023 |
identifier_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues, v. 83, n. 17-18, p. 616-629, 2020. 1087-2620 1528-7394 10.1080/15287394.2020.1805078 2-s2.0-85089456708 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Toxicology and Environmental Health - Part A: Current Issues |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
616-629 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129182425677824 |