Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria

Autores
Buzaleh, A.M.; Morán-Jiménez, M.J.; García-Bravo, M.; Sampedro, A.; Batlle, A.M.D.C.; Enríquez De Salamanca, R.; Fontanellas, A.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fech m1Pas) mice, was evaluated by measuring the activity of δ-Aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias. Copyright © 2009 C.M.B. Edition.
Fil:Buzaleh, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Batlle, A.M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fuente
Cell. Mol. Biol. 2009;55(1):38-44
Materia
Cytochrome P-450
Erythropoietic protoporphyria
Glutathione
Heme metabolism
Isoflurane
5 aminolevulinate synthase
cytochrome P450
cytochrome P450 2E1
ferrochelatase
glutathione
heme oxygenase
isoflurane
porphobilinogen deaminase
porphyrin
animal experiment
animal model
animal tissue
article
controlled study
drug effect
drug mechanism
enzyme activity
erythropoietic protoporphyria
heme synthesis
male
mouse
nonhuman
signal transduction
urinary excretion
5-Aminolevulinate Synthetase
Animals
Enzyme Activation
Enzyme Induction
Glutathione
Heme Oxygenase (Decyclizing)
Hydroxymethylbilane Synthase
Isoflurane
Liver
Mice
Mice, Mutant Strains
Oxidative Stress
Protoporphyria, Erythropoietic
Animalia
Mus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/2.5/ar
Repositorio
Biblioteca Digital (UBA-FCEN)
Institución
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identificador
paperaa:paper_01455680_v55_n1_p38_Buzaleh

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oai_identifier_str paperaa:paper_01455680_v55_n1_p38_Buzaleh
network_acronym_str BDUBAFCEN
repository_id_str 1896
network_name_str Biblioteca Digital (UBA-FCEN)
spelling Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyriaBuzaleh, A.M.Morán-Jiménez, M.J.García-Bravo, M.Sampedro, A.Batlle, A.M.D.C.Enríquez De Salamanca, R.Fontanellas, A.Cytochrome P-450Erythropoietic protoporphyriaGlutathioneHeme metabolismIsoflurane5 aminolevulinate synthasecytochrome P450cytochrome P450 2E1ferrochelataseglutathioneheme oxygenaseisofluraneporphobilinogen deaminaseporphyrinanimal experimentanimal modelanimal tissuearticlecontrolled studydrug effectdrug mechanismenzyme activityerythropoietic protoporphyriaheme synthesismalemousenonhumansignal transductionurinary excretion5-Aminolevulinate SynthetaseAnimalsEnzyme ActivationEnzyme InductionGlutathioneHeme Oxygenase (Decyclizing)Hydroxymethylbilane SynthaseIsofluraneLiverMiceMice, Mutant StrainsOxidative StressProtoporphyria, ErythropoieticAnimaliaMusErythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fech m1Pas) mice, was evaluated by measuring the activity of δ-Aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias. Copyright © 2009 C.M.B. Edition.Fil:Buzaleh, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Batlle, A.M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_BuzalehCell. Mol. Biol. 2009;55(1):38-44reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-09-29T13:42:55Zpaperaa:paper_01455680_v55_n1_p38_BuzalehInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-09-29 13:42:56.224Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse
dc.title.none.fl_str_mv Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
title Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
spellingShingle Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
Buzaleh, A.M.
Cytochrome P-450
Erythropoietic protoporphyria
Glutathione
Heme metabolism
Isoflurane
5 aminolevulinate synthase
cytochrome P450
cytochrome P450 2E1
ferrochelatase
glutathione
heme oxygenase
isoflurane
porphobilinogen deaminase
porphyrin
animal experiment
animal model
animal tissue
article
controlled study
drug effect
drug mechanism
enzyme activity
erythropoietic protoporphyria
heme synthesis
male
mouse
nonhuman
signal transduction
urinary excretion
5-Aminolevulinate Synthetase
Animals
Enzyme Activation
Enzyme Induction
Glutathione
Heme Oxygenase (Decyclizing)
Hydroxymethylbilane Synthase
Isoflurane
Liver
Mice
Mice, Mutant Strains
Oxidative Stress
Protoporphyria, Erythropoietic
Animalia
Mus
title_short Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
title_full Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
title_fullStr Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
title_full_unstemmed Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
title_sort Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
dc.creator.none.fl_str_mv Buzaleh, A.M.
Morán-Jiménez, M.J.
García-Bravo, M.
Sampedro, A.
Batlle, A.M.D.C.
Enríquez De Salamanca, R.
Fontanellas, A.
author Buzaleh, A.M.
author_facet Buzaleh, A.M.
Morán-Jiménez, M.J.
García-Bravo, M.
Sampedro, A.
Batlle, A.M.D.C.
Enríquez De Salamanca, R.
Fontanellas, A.
author_role author
author2 Morán-Jiménez, M.J.
García-Bravo, M.
Sampedro, A.
Batlle, A.M.D.C.
Enríquez De Salamanca, R.
Fontanellas, A.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cytochrome P-450
Erythropoietic protoporphyria
Glutathione
Heme metabolism
Isoflurane
5 aminolevulinate synthase
cytochrome P450
cytochrome P450 2E1
ferrochelatase
glutathione
heme oxygenase
isoflurane
porphobilinogen deaminase
porphyrin
animal experiment
animal model
animal tissue
article
controlled study
drug effect
drug mechanism
enzyme activity
erythropoietic protoporphyria
heme synthesis
male
mouse
nonhuman
signal transduction
urinary excretion
5-Aminolevulinate Synthetase
Animals
Enzyme Activation
Enzyme Induction
Glutathione
Heme Oxygenase (Decyclizing)
Hydroxymethylbilane Synthase
Isoflurane
Liver
Mice
Mice, Mutant Strains
Oxidative Stress
Protoporphyria, Erythropoietic
Animalia
Mus
topic Cytochrome P-450
Erythropoietic protoporphyria
Glutathione
Heme metabolism
Isoflurane
5 aminolevulinate synthase
cytochrome P450
cytochrome P450 2E1
ferrochelatase
glutathione
heme oxygenase
isoflurane
porphobilinogen deaminase
porphyrin
animal experiment
animal model
animal tissue
article
controlled study
drug effect
drug mechanism
enzyme activity
erythropoietic protoporphyria
heme synthesis
male
mouse
nonhuman
signal transduction
urinary excretion
5-Aminolevulinate Synthetase
Animals
Enzyme Activation
Enzyme Induction
Glutathione
Heme Oxygenase (Decyclizing)
Hydroxymethylbilane Synthase
Isoflurane
Liver
Mice
Mice, Mutant Strains
Oxidative Stress
Protoporphyria, Erythropoietic
Animalia
Mus
dc.description.none.fl_txt_mv Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fech m1Pas) mice, was evaluated by measuring the activity of δ-Aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias. Copyright © 2009 C.M.B. Edition.
Fil:Buzaleh, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Batlle, A.M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
description Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fech m1Pas) mice, was evaluated by measuring the activity of δ-Aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias. Copyright © 2009 C.M.B. Edition.
publishDate 2009
dc.date.none.fl_str_mv 2009
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/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh
url http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.5/ar
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/ar
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Cell. Mol. Biol. 2009;55(1):38-44
reponame:Biblioteca Digital (UBA-FCEN)
instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
reponame_str Biblioteca Digital (UBA-FCEN)
collection Biblioteca Digital (UBA-FCEN)
instname_str Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron_str UBA-FCEN
institution UBA-FCEN
repository.name.fl_str_mv Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
repository.mail.fl_str_mv ana@bl.fcen.uba.ar
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