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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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 |
work_keys_str_mv |
AT martinezmariadelcarmen hepaticdamageandoxidativestressinducedbygriseofulvininmice AT afonsosusanagraciela hepaticdamageandoxidativestressinducedbygriseofulvininmice AT buzalehanamaria hepaticdamageandoxidativestressinducedbygriseofulvininmice AT batllealciramariadelcarmen hepaticdamageandoxidativestressinducedbygriseofulvininmice |
_version_ |
1768544034312159232 |