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Abstract:

Brain cytochrome P450 (CYP) metabolizes a variety of drugs to produce their pharmacological effects within the brain. We have previously observed that porphyrinogenic agents altered CYP levels in brain. The aim of this work was to further study the involvement of mice brain mitochondrial and microsomal Phase I drug metabolizing system when porphyrinogenic agents, such as Enflurane, Isoflurane, allylisopropylacetamide, veronal, ethanol, and Griseofulvin were administered. To this end, CYP2E1, CYP2B1, and CYP3A4 expression were measured. NADPH cytochrome P450 reductase (CPR) expression was also determined. Western Blots were performed in microsomes and mitochondria of whole brain. Some of the drugs studied altered expression mainly in microsomes. Chronic Isoflurane augmented mitochondrial isoform, although this anaesthetic diminished microsomal expression. Ethanol and topical Griseofulvin affected expression in microsomes but not in mitochondria. CYP2E1 mitochondrial activity was induced by acute Enflurane; while the activity of the microsomal protein was enhanced in alcoholised animals. Ethanol also induced CYP2E1 expression in microsomes, although Isoflurane provoked opposite effects in mitochondria and microsomes. Expression of CPR was also induced. Several reports support an emergent role of CYP enzymes in the pathogenesis of neurological disorders, so CYP response in brain could be one of the multiples factors influencing porphyria acute attacks. © 2015 Published by NRC Research Press.

Registro:

Documento: Artículo
Título:Cytochrome P450 expression in mouse brain: Specific isoenzymes involved in Phase i metabolizing system of porphyrinogenic agents in both microsomes and mitochondria
Autor:Lavandera, J.; Ruspini, S.; Batlle, A.; Buzaleh, A.M.
Filiación:Cátedra de Bromatología y Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional Del Litoral, Santa Fe, Argentina
Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), CONICET, Universidad de Buenos Aires, Av. Córdoba 2351, Buenos Aires, 1120, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
Palabras clave:Brain; Cytochrome P450; Porphyrinogenic agents; Volatile anaesthetics; Anesthetics; Brain; Enzymes; Ethanol; Mammals; Cytochrome p450; Microsomal proteins; Mitochondrial activity; NADPH-cytochrome P450 reductase; Neurological disorders; Pharmacological effects; Western blots; Whole brains; Mitochondria; alcohol; allylisopropylacetamide; barbital; cytochrome P450 2B1; cytochrome P450 2E1; cytochrome P450 3A4; drug metabolizing enzyme; enflurane; griseofulvin; isoenzyme; isoflurane; porphyrinogen; reduced nicotinamide adenine dinucleotide ferrihemoprotein reductase; cytochrome P450; cytochrome P450 2B1; cytochrome P450 2E1; cytochrome P450 3A; isoenzyme; adult; animal experiment; Article; brain; brain microsome; brain mitochondrion; cell fractionation; controlled study; immunoblotting; male; mouse; nonhuman; protein expression; Western blotting; animal; brain; drug effects; enzymology; metabolism; microsome; mitochondrion; Animalia; Mus; Animals; Brain; Cytochrome P-450 CYP2B1; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Isoenzymes; Male; Mice; Microsomes; Mitochondria
Año:2015
Volumen:93
Número:1
Página de inicio:102
Página de fin:107
DOI: http://dx.doi.org/10.1139/bcb-2014-0088
Título revista:Biochemistry and Cell Biology
Título revista abreviado:Biochem. Cell Biol.
ISSN:08298211
CODEN:BCBIE
CAS:alcohol, 64-17-5; allylisopropylacetamide, 299-78-5; barbital, 144-02-5, 57-44-3; cytochrome P450 2B1, 330207-10-8; cytochrome P450 3A4, 329736-03-0; enflurane, 13838-16-9; griseofulvin, 126-07-8; isoflurane, 26675-46-7; porphyrinogen, 4396-11-6; cytochrome P450, 9035-51-2; cytochrome P450 3A, 329322-82-9; Cytochrome P-450 CYP2B1; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Isoenzymes
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08298211_v93_n1_p102_Lavandera

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Citas:

---------- APA ----------
Lavandera, J., Ruspini, S., Batlle, A. & Buzaleh, A.M. (2015) . Cytochrome P450 expression in mouse brain: Specific isoenzymes involved in Phase i metabolizing system of porphyrinogenic agents in both microsomes and mitochondria. Biochemistry and Cell Biology, 93(1), 102-107.
http://dx.doi.org/10.1139/bcb-2014-0088
---------- CHICAGO ----------
Lavandera, J., Ruspini, S., Batlle, A., Buzaleh, A.M. "Cytochrome P450 expression in mouse brain: Specific isoenzymes involved in Phase i metabolizing system of porphyrinogenic agents in both microsomes and mitochondria" . Biochemistry and Cell Biology 93, no. 1 (2015) : 102-107.
http://dx.doi.org/10.1139/bcb-2014-0088
---------- MLA ----------
Lavandera, J., Ruspini, S., Batlle, A., Buzaleh, A.M. "Cytochrome P450 expression in mouse brain: Specific isoenzymes involved in Phase i metabolizing system of porphyrinogenic agents in both microsomes and mitochondria" . Biochemistry and Cell Biology, vol. 93, no. 1, 2015, pp. 102-107.
http://dx.doi.org/10.1139/bcb-2014-0088
---------- VANCOUVER ----------
Lavandera, J., Ruspini, S., Batlle, A., Buzaleh, A.M. Cytochrome P450 expression in mouse brain: Specific isoenzymes involved in Phase i metabolizing system of porphyrinogenic agents in both microsomes and mitochondria. Biochem. Cell Biol. 2015;93(1):102-107.
http://dx.doi.org/10.1139/bcb-2014-0088