Hepatic Damage Induced by Griseofulvin as a Murine Model of Protoporphyia. Effect of Antioxidants

Abstract

Erythropoietic Protoporphyria (EPP) is a disease associated with ferrochelatase deficiency, characterized by the 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 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: Trolox (Tx), Ascorbic acid (Asc), the combination Tx and Asc, Melatonin (Mel) and the polyphenols: Elagic acid, Quercetin, Chlorogenic acid, Caffeic acid, Galic acid and Ferulic acid on heme biosynthesis, 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 of 5-aminolevulinic acid synthetase 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.