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
- 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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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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1844618735127625728 |
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13.070432 |