Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria
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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2009
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n1_p38_Buzaleh http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh |
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paper:paper_01455680_v55_n1_p38_Buzaleh2023-06-08T15:12:26Z Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria Buzaleh, Ana María Batlle, Alcira María del Carmen 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n1_p38_Buzaleh 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) |
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, Ana María Batlle, Alcira María del Carmen 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. |
author |
Buzaleh, Ana María Batlle, Alcira María del Carmen |
author_facet |
Buzaleh, Ana María Batlle, Alcira María del Carmen |
author_sort |
Buzaleh, Ana María |
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 |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n1_p38_Buzaleh http://hdl.handle.net/20.500.12110/paper_01455680_v55_n1_p38_Buzaleh |
work_keys_str_mv |
AT buzalehanamaria inductionofhepaticaminolevulinateacidsynthetaseactivitybyisofluraneinageneticmodelforerythropoieticprotoporphyria AT batllealciramariadelcarmen inductionofhepaticaminolevulinateacidsynthetaseactivitybyisofluraneinageneticmodelforerythropoieticprotoporphyria |
_version_ |
1768543414490497024 |