title: Protective action of antioxidants on hepatic damage induced by griseofulvin.
abstract: Erythropoietic protoporphyria (EPP) is a disease associated with ferrochelatase deficiency and characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver, and skin. In some cases, a severe hepatic failure and cholestasis were observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed by cellular damage as wells as necrotic and inflammatory processes. The antioxidant defense system was also altered. The aim was to evaluate the possible protective effect of different antioxidant compounds: trolox (Tx), ascorbic acid (Asc), the combination Tx and Asc, melatonin (Mel), and the polyphenols: ellagic acid, quercetin, chlorogenic acid, caffeic acid, gallic acid, and ferulic acid on liver damage and oxidative stress markers in a mouse model of EPP. Coadministration of Gris with Tx, Asc, and its combination, or Mel mainly affected heme biosynthetic pathway, resulting in a decrease in ALA-S activity which was increased by Gris, while the tested polyphenols exerted a protective effect on oxidative stress, decreasing lipid peroxidation and the activity of some antioxidant enzymes. In conclusion, antioxidant compounds can only protect partially against the liver damage induced by Gris, reducing oxidative stress or acting on heme regulation.
authors: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160 Pab II, 1428 Buenos Aires, Argentina.
authors: M del C
authors: Mdel C
authors: Martinez
authors: Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Avenida, Córdoba 2351 1er subsuelo, 1120 Buenos Aires, Argentina.
authors: S G
authors: SG
authors: Afonso
authors: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160 Pab II, 1428 Buenos Aires, Argentina ; Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Avenida, Córdoba 2351 1er subsuelo, 1120 Buenos Aires, Argentina.
authors: A M
authors: AM
authors: Buzaleh
authors: Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Avenida, Córdoba 2351 1er subsuelo, 1120 Buenos Aires, Argentina.
authors: A
authors: A
authors: Batlle
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006118:Griseofulvin / Q000009:adverse effects*; D006418:Heme / Q000378:metabolism; D008297:Male; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D000975:Antioxidants; D015415:Biomarkers; D006118:Griseofulvin; D006418:Heme; D013482:Superoxide Dismutase; D005978:Glutathione