CONICET | Buscador de Institutos y Recursos Humanos

Erythropoietic Protoporphyria (EPP) is a disease associated with a deficiency of the enzyme ferrochelatase, leading to the accumulation of protoporphyrin IX (PP) in erythrocytes, liver and skin. The most serious manifestation is the progressive liver failure, cholestasis and deposition of PP in the canalicular bile. The antifungal griseofulvin (Gris), develops in animals, a model of EPP with liver manifestations. In a previous work, we demonstrated that the administration of Gris to mice induces oxidative stress and severe liver damage. Treatment with polyphenols, such as Chlorogenic acid (CA), protected the liver from lipid peroxidation, while Desoxycholic acid (DA) decreased PP accumulation in liver. The aim of this work was to evaluate the possible protective effect of some antioxidants and bile acids on markers of liver damage and oxidative stress in our mouse model of EPP. Animals fed with 0.5% of Gris received the antioxidants: Trolox (Tx) (2mg/100ml), Ascorbic acid (Asc) (12mg/100ml), Melatonin (5mg/ kg) and the combinations of CA (50mg / l) plus DA (0.33% w/w in the diet) or CA plus Ursodeoxycholic acid (UA) (0.2% w/w in the diet). Antioxidants decreased 50% the induction of ALA-S, while Tx and As reduced 20% lipid peroxidation provoked by Gris. Asc alone or in combination with Tx reduced 50% Glutathione levels and 27% Glutathione- S-Transferase activity. Tx alone also diminished Glutathione Reductase (33%) and Superoxide Dismutase (26%) activities. The combination of AC plus AD reversed 95% accumulation of PP in liver and prevented the induction of some parameters of the antioxidant system, while the combination of AC plus AU acted only at the level of oxidative stress. Results here presented indicate that treatments with the antioxidants or bile acids were able to partially protect the liver damage produced by Gris, reflected by diminishing oxidative stress, increasing porphyrins excretion or affecting haem regulation