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

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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 xenobioti...

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Autores principales:	Buzaleh, A.M., Morán-Jiménez, M.J., García-Bravo, M., Sampedro, A., Batlle, A.M.D.C., Enríquez De Salamanca, R., Fontanellas, A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2009
Materias:	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 Heme Oxygenase (Decyclizing) Hydroxymethylbilane Synthase Liver Mice Mice, Mutant Strains Oxidative Stress Protoporphyria, Erythropoietic Animalia Mus
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_01455680_v55_n1_p38_Buzaleh2023-06-12T16:46:44Z Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria Cell. Mol. Biol. 2009;55(1):38-44 Buzaleh, A.M. Morán-Jiménez, M.J. García-Bravo, M. Sampedro, A. Batlle, A.M.D.C. Enríquez De Salamanca, R. Fontanellas, A. 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 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. 2009 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
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
spellingShingle	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 Buzaleh, A.M. Morán-Jiménez, M.J. García-Bravo, M. Sampedro, A. Batlle, A.M.D.C. Enríquez De Salamanca, R. Fontanellas, A. Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
topic_facet	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
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.
format	Artículo Artículo publishedVersion
author	Buzaleh, A.M. Morán-Jiménez, M.J. García-Bravo, M. Sampedro, A. Batlle, A.M.D.C. Enríquez De Salamanca, R. Fontanellas, A.
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_sort	Buzaleh, A.M.
title	Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
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
publishDate	2009
url	http://hdl.handle.net/20.500.12110/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 protoporphyria

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