Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system
Acute attacks of porphyria are most commonly precipitated by events that decrease heme concentrations. Enzyme inducing-drugs are the most important triggering factors, particularly in relation to anaesthesia. We have reported previously that Enflurane and Isoflurane produced significant heme metabol...
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todo:paper_01455680_v55_n2_p140_Sampayo2023-10-03T15:00:08Z Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system Sampayo, R. Lavandera, J.V. Batlle, A. Buzaleh, A.M. 5-aminolevulinic acid synthetase Cytochrome P450 Heme metabolism PBG deaminase heme oxygenase Sevoflurane 5 aminolevulinate synthase cytochrome P450 2E1 heme heme oxygenase porphobilinogen deaminase sevoflurane acute intermittent porphyria animal experiment animal tissue article controlled study drug metabolism enzyme activity enzyme induction male mouse nonhuman oxidative stress Western blotting 5-Aminolevulinate Synthetase Anesthetics, Inhalation Animals Cytochrome P-450 CYP2E1 Heme Heme Oxygenase (Decyclizing) Hydroxymethylbilane Synthase Liver Male Methyl Ethers Mice Oxidative Stress Animalia Mus Acute attacks of porphyria are most commonly precipitated by events that decrease heme concentrations. Enzyme inducing-drugs are the most important triggering factors, particularly in relation to anaesthesia. We have reported previously that Enflurane and Isoflurane produced significant heme metabolism alterations, indicating that the use of these anaesthetics in porphyric patients should be avoided. The aim of this work was to evaluate the effect of the anaesthetic Sevoflurane on heme pathway and drug metabolizing Phase I system in mice. To this end, animals received different doses of the anaesthetic (1-2 ml/kg) and were sacrificed at different times (5-60 min). Data revealed important alterations in the enzymes involved in Acute Intermittent Porphyria, such as an induction in hepatic 5-Aminolevulinic acid synthetase activity and a diminished Porphobilinogen deaminase activity in liver and blood 20 minutes after Sevoflurane administration to mice in a dose of 1.5 ml/kg. Heme oxygenase activity was also induced, indicating the onset of oxidative stress. Total CYP levels and CYP2E1 expression were enhanced. As a consequence of these events, heme free pool would be depleted. In conclusion, our results in mice would suggest that Sevoflurane should be used with caution and very careful control in porphyric patients. Copyright © 2009 C.M.B. Edition. Fil:Lavandera, J.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Buzaleh, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01455680_v55_n2_p140_Sampayo |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
5-aminolevulinic acid synthetase Cytochrome P450 Heme metabolism PBG deaminase heme oxygenase Sevoflurane 5 aminolevulinate synthase cytochrome P450 2E1 heme heme oxygenase porphobilinogen deaminase sevoflurane acute intermittent porphyria animal experiment animal tissue article controlled study drug metabolism enzyme activity enzyme induction male mouse nonhuman oxidative stress Western blotting 5-Aminolevulinate Synthetase Anesthetics, Inhalation Animals Cytochrome P-450 CYP2E1 Heme Heme Oxygenase (Decyclizing) Hydroxymethylbilane Synthase Liver Male Methyl Ethers Mice Oxidative Stress Animalia Mus |
| spellingShingle |
5-aminolevulinic acid synthetase Cytochrome P450 Heme metabolism PBG deaminase heme oxygenase Sevoflurane 5 aminolevulinate synthase cytochrome P450 2E1 heme heme oxygenase porphobilinogen deaminase sevoflurane acute intermittent porphyria animal experiment animal tissue article controlled study drug metabolism enzyme activity enzyme induction male mouse nonhuman oxidative stress Western blotting 5-Aminolevulinate Synthetase Anesthetics, Inhalation Animals Cytochrome P-450 CYP2E1 Heme Heme Oxygenase (Decyclizing) Hydroxymethylbilane Synthase Liver Male Methyl Ethers Mice Oxidative Stress Animalia Mus Sampayo, R. Lavandera, J.V. Batlle, A. Buzaleh, A.M. Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| topic_facet |
5-aminolevulinic acid synthetase Cytochrome P450 Heme metabolism PBG deaminase heme oxygenase Sevoflurane 5 aminolevulinate synthase cytochrome P450 2E1 heme heme oxygenase porphobilinogen deaminase sevoflurane acute intermittent porphyria animal experiment animal tissue article controlled study drug metabolism enzyme activity enzyme induction male mouse nonhuman oxidative stress Western blotting 5-Aminolevulinate Synthetase Anesthetics, Inhalation Animals Cytochrome P-450 CYP2E1 Heme Heme Oxygenase (Decyclizing) Hydroxymethylbilane Synthase Liver Male Methyl Ethers Mice Oxidative Stress Animalia Mus |
| description |
Acute attacks of porphyria are most commonly precipitated by events that decrease heme concentrations. Enzyme inducing-drugs are the most important triggering factors, particularly in relation to anaesthesia. We have reported previously that Enflurane and Isoflurane produced significant heme metabolism alterations, indicating that the use of these anaesthetics in porphyric patients should be avoided. The aim of this work was to evaluate the effect of the anaesthetic Sevoflurane on heme pathway and drug metabolizing Phase I system in mice. To this end, animals received different doses of the anaesthetic (1-2 ml/kg) and were sacrificed at different times (5-60 min). Data revealed important alterations in the enzymes involved in Acute Intermittent Porphyria, such as an induction in hepatic 5-Aminolevulinic acid synthetase activity and a diminished Porphobilinogen deaminase activity in liver and blood 20 minutes after Sevoflurane administration to mice in a dose of 1.5 ml/kg. Heme oxygenase activity was also induced, indicating the onset of oxidative stress. Total CYP levels and CYP2E1 expression were enhanced. As a consequence of these events, heme free pool would be depleted. In conclusion, our results in mice would suggest that Sevoflurane should be used with caution and very careful control in porphyric patients. Copyright © 2009 C.M.B. Edition. |
| format |
JOUR |
| author |
Sampayo, R. Lavandera, J.V. Batlle, A. Buzaleh, A.M. |
| author_facet |
Sampayo, R. Lavandera, J.V. Batlle, A. Buzaleh, A.M. |
| author_sort |
Sampayo, R. |
| title |
Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| title_short |
Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| title_full |
Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| title_fullStr |
Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| title_full_unstemmed |
Sevoflurane: Its action on heme metabolism and phase I drug metabolizing system |
| title_sort |
sevoflurane: its action on heme metabolism and phase i drug metabolizing system |
| url |
http://hdl.handle.net/20.500.12110/paper_01455680_v55_n2_p140_Sampayo |
| work_keys_str_mv |
AT sampayor sevofluraneitsactiononhememetabolismandphaseidrugmetabolizingsystem AT lavanderajv sevofluraneitsactiononhememetabolismandphaseidrugmetabolizingsystem AT batllea sevofluraneitsactiononhememetabolismandphaseidrugmetabolizingsystem AT buzaleham sevofluraneitsactiononhememetabolismandphaseidrugmetabolizingsystem |
| _version_ |
1782026018991636480 |