Hepatic damage and oxidative stress induced by griseofulvin in mice

Erythropoietic Protoporphyria (EPP) is a disease associated with ferrochelatase deficiency, which produces accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver and skin. In some cases, a severe hepatic failure and cholestasis was observed. Griseofulvin (Gris) develops an experimental...

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Autores principales: Martínez, María del Carmen, Afonso, Susana Graciela, Buzaleh, Ana María, Batlle, Alcira María del Carmen
Publicado: 2009
Materias:
Mus
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n2_p127_Martinez
http://hdl.handle.net/20.500.12110/paper_01455680_v55_n2_p127_Martinez
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spelling paper:paper_01455680_v55_n2_p127_Martinez2023-06-08T15:12:27Z Hepatic damage and oxidative stress induced by griseofulvin in mice Martínez, María del Carmen Afonso, Susana Graciela Buzaleh, Ana María Batlle, Alcira María del Carmen Erythropoietic Protoporphyria Griseofulvin Heme metabolism Liver damage Oxidative stress 5 aminolevulinate synthase alanine aminotransferase alkaline phosphatase aspartate aminotransferase catalase cytochrome P450 1A2 cytochrome P450 2A6 cytochrome P450 2C9 cytochrome P450 2E1 cytochrome P450 3A4 glutathione glutathione peroxidase glutathione reductase glutathione transferase griseofulvin heme heme oxygenase malonaldehyde protoporphyrin reactive oxygen metabolite superoxide dismutase tryptophan 2,3 dioxygenase alanine aminotransferase blood level alkaline phosphatase blood level animal experiment animal model animal tissue antioxidant activity article aspartate aminotransferase blood level blood level body weight controlled study enzyme activity enzyme induction erythropoietic protoporphyria experimental mouse feces level histopathology liver injury liver level liver weight male mouse nonhuman oxidation reduction reaction oxidative stress Animals Antifungal Agents Aryl Hydrocarbon Hydroxylases Cytochrome P-450 CYP3A Disease Models, Animal Griseofulvin Heme Heme Oxygenase (Decyclizing) Immunohistochemistry Liver Male Mice Oxidative Stress Protoporphyria, Erythropoietic Protoporphyrins Tryptophan Oxygenase Animalia Mus Erythropoietic Protoporphyria (EPP) is a disease associated with ferrochelatase deficiency, which produces accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver and skin. In some cases, a severe hepatic failure and cholestasis was observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in animals. The aim of this work was to further characterize this model studying its effect on different metabolisms in mice Gris feeding (0-2.5%, 7 and 14 days). PROTO IX accumulation in liver, blood and feces, induction of ALA-S activity, and a low rate of Holo/Apo tryptophan pyrrolase activity was produced, indicating a reduction of free heme pool. The progressive liver injury was reflected by the aspect and the enlargement of liver and the induction of hepatic damage. Liver redox balance was altered due to porphyrin high concentrations; as a consequence, the antioxidant defense system was disrupted. Heme oxygenase was also induced, however, at higher concentrations of antifungal, the free heme pool would be so depleted that this enzyme would not be necessary. In conclusion, our model of Protoporphyria produced liver alterations similar to those found in EPP patients. Copyright © 2009 C.M.B. Edition. Fil:Martinez, M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Afonso, S.G. 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. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n2_p127_Martinez http://hdl.handle.net/20.500.12110/paper_01455680_v55_n2_p127_Martinez
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Erythropoietic Protoporphyria
Griseofulvin
Heme metabolism
Liver damage
Oxidative stress
5 aminolevulinate synthase
alanine aminotransferase
alkaline phosphatase
aspartate aminotransferase
catalase
cytochrome P450 1A2
cytochrome P450 2A6
cytochrome P450 2C9
cytochrome P450 2E1
cytochrome P450 3A4
glutathione
glutathione peroxidase
glutathione reductase
glutathione transferase
griseofulvin
heme
heme oxygenase
malonaldehyde
protoporphyrin
reactive oxygen metabolite
superoxide dismutase
tryptophan 2,3 dioxygenase
alanine aminotransferase blood level
alkaline phosphatase blood level
animal experiment
animal model
animal tissue
antioxidant activity
article
aspartate aminotransferase blood level
blood level
body weight
controlled study
enzyme activity
enzyme induction
erythropoietic protoporphyria
experimental mouse
feces level
histopathology
liver injury
liver level
liver weight
male
mouse
nonhuman
oxidation reduction reaction
oxidative stress
Animals
Antifungal Agents
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP3A
Disease Models, Animal
Griseofulvin
Heme
Heme Oxygenase (Decyclizing)
Immunohistochemistry
Liver
Male
Mice
Oxidative Stress
Protoporphyria, Erythropoietic
Protoporphyrins
Tryptophan Oxygenase
Animalia
Mus
spellingShingle Erythropoietic Protoporphyria
Griseofulvin
Heme metabolism
Liver damage
Oxidative stress
5 aminolevulinate synthase
alanine aminotransferase
alkaline phosphatase
aspartate aminotransferase
catalase
cytochrome P450 1A2
cytochrome P450 2A6
cytochrome P450 2C9
cytochrome P450 2E1
cytochrome P450 3A4
glutathione
glutathione peroxidase
glutathione reductase
glutathione transferase
griseofulvin
heme
heme oxygenase
malonaldehyde
protoporphyrin
reactive oxygen metabolite
superoxide dismutase
tryptophan 2,3 dioxygenase
alanine aminotransferase blood level
alkaline phosphatase blood level
animal experiment
animal model
animal tissue
antioxidant activity
article
aspartate aminotransferase blood level
blood level
body weight
controlled study
enzyme activity
enzyme induction
erythropoietic protoporphyria
experimental mouse
feces level
histopathology
liver injury
liver level
liver weight
male
mouse
nonhuman
oxidation reduction reaction
oxidative stress
Animals
Antifungal Agents
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP3A
Disease Models, Animal
Griseofulvin
Heme
Heme Oxygenase (Decyclizing)
Immunohistochemistry
Liver
Male
Mice
Oxidative Stress
Protoporphyria, Erythropoietic
Protoporphyrins
Tryptophan Oxygenase
Animalia
Mus
Martínez, María del Carmen
Afonso, Susana Graciela
Buzaleh, Ana María
Batlle, Alcira María del Carmen
Hepatic damage and oxidative stress induced by griseofulvin in mice
topic_facet Erythropoietic Protoporphyria
Griseofulvin
Heme metabolism
Liver damage
Oxidative stress
5 aminolevulinate synthase
alanine aminotransferase
alkaline phosphatase
aspartate aminotransferase
catalase
cytochrome P450 1A2
cytochrome P450 2A6
cytochrome P450 2C9
cytochrome P450 2E1
cytochrome P450 3A4
glutathione
glutathione peroxidase
glutathione reductase
glutathione transferase
griseofulvin
heme
heme oxygenase
malonaldehyde
protoporphyrin
reactive oxygen metabolite
superoxide dismutase
tryptophan 2,3 dioxygenase
alanine aminotransferase blood level
alkaline phosphatase blood level
animal experiment
animal model
animal tissue
antioxidant activity
article
aspartate aminotransferase blood level
blood level
body weight
controlled study
enzyme activity
enzyme induction
erythropoietic protoporphyria
experimental mouse
feces level
histopathology
liver injury
liver level
liver weight
male
mouse
nonhuman
oxidation reduction reaction
oxidative stress
Animals
Antifungal Agents
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP3A
Disease Models, Animal
Griseofulvin
Heme
Heme Oxygenase (Decyclizing)
Immunohistochemistry
Liver
Male
Mice
Oxidative Stress
Protoporphyria, Erythropoietic
Protoporphyrins
Tryptophan Oxygenase
Animalia
Mus
description Erythropoietic Protoporphyria (EPP) is a disease associated with ferrochelatase deficiency, which produces accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver and skin. In some cases, a severe hepatic failure and cholestasis was observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in animals. The aim of this work was to further characterize this model studying its effect on different metabolisms in mice Gris feeding (0-2.5%, 7 and 14 days). PROTO IX accumulation in liver, blood and feces, induction of ALA-S activity, and a low rate of Holo/Apo tryptophan pyrrolase activity was produced, indicating a reduction of free heme pool. The progressive liver injury was reflected by the aspect and the enlargement of liver and the induction of hepatic damage. Liver redox balance was altered due to porphyrin high concentrations; as a consequence, the antioxidant defense system was disrupted. Heme oxygenase was also induced, however, at higher concentrations of antifungal, the free heme pool would be so depleted that this enzyme would not be necessary. In conclusion, our model of Protoporphyria produced liver alterations similar to those found in EPP patients. Copyright © 2009 C.M.B. Edition.
author Martínez, María del Carmen
Afonso, Susana Graciela
Buzaleh, Ana María
Batlle, Alcira María del Carmen
author_facet Martínez, María del Carmen
Afonso, Susana Graciela
Buzaleh, Ana María
Batlle, Alcira María del Carmen
author_sort Martínez, María del Carmen
title Hepatic damage and oxidative stress induced by griseofulvin in mice
title_short Hepatic damage and oxidative stress induced by griseofulvin in mice
title_full Hepatic damage and oxidative stress induced by griseofulvin in mice
title_fullStr Hepatic damage and oxidative stress induced by griseofulvin in mice
title_full_unstemmed Hepatic damage and oxidative stress induced by griseofulvin in mice
title_sort hepatic damage and oxidative stress induced by griseofulvin in mice
publishDate 2009
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v55_n2_p127_Martinez
http://hdl.handle.net/20.500.12110/paper_01455680_v55_n2_p127_Martinez
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AT afonsosusanagraciela hepaticdamageandoxidativestressinducedbygriseofulvininmice
AT buzalehanamaria hepaticdamageandoxidativestressinducedbygriseofulvininmice
AT batllealciramariadelcarmen hepaticdamageandoxidativestressinducedbygriseofulvininmice
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