title: Experimental protoporphyria: effect of bile acids on liver damage induced by griseofulvin.
abstract: The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or ursodeoxycholic (URSO). The administration of Gris alone increased the activities of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST), as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Intendente Güiraldes 2160, 1428 Buenos Aires, Argentina.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Martinez
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET-UBA, Avenida Córdoba 2351, 1120 Buenos Aires, Argentina.
authors.forename: Silvina Fernanda
authors.initials: SF
authors.lastname: Ruspini
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET-UBA, Avenida Córdoba 2351, 1120 Buenos Aires, Argentina.
authors.forename: Susana Graciela
authors.initials: SG
authors.lastname: Afonso
authors.affiliation: Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Intendente Güiraldes 2160, 1428 Buenos Aires, Argentina ; Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET-UBA, Avenida Córdoba 2351, 1120 Buenos Aires, Argentina.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Buzaleh
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET-UBA, Avenida Córdoba 2351, 1120 Buenos Aires, Argentina.
authors.forename: Alcira
authors.identifier: 0000-0002-4894-8955
authors.initials: A
authors.lastname: Batlle
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage; D003685:Dehydrocholic Acid / Q000008:administration & dosage; D003840:Deoxycholic Acid / Q000008:administration & dosage; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006118:Griseofulvin / Q000633:toxicity; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011166:Porphyrins / Q000378:metabolism; D046351:Protoporphyria, Erythropoietic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage
chemical_list: D011166:Porphyrins; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D006118:Griseofulvin; D014580:Ursodeoxycholic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D003685:Dehydrocholic Acid