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

MARÍA DEL CARMEN MARTINEZ; SUSANA GRACIELA AFONSO; ALCIRA BATLLE; ANA MARIA BUZALEH

Innovations in Science and Technology

Book Publisher International

Año: 2022; p. 75 - 90

Erythropoietic Protoporphyria (EPP) is a disease associated with ferrochelatase deficiency,characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver and skin. Insome cases, a severe hepatic failure and cholestasis was observed. Griseofulvin (Gris) develops anexperimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed bycellular damage as wells as necrotic and inflammatory processes. The antioxidant defense systemwas 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: Elagicacid, Quercetin, Chlorogenic acid, Caffeic acid, Galic acid and Ferulic acid on heme biosynthesis, liverdamage and oxidative stress markers in a mouse model of EPP.Coadministration of Gris with Tx, Asc, and its combination, or Mel mainly affected heme biosyntheticpathway, resulting in a decrease of 5-aminolevulinic acid synthetase activity which was increased byGris, while the tested polyphenols exerted a protective effect on oxidative stress, decreasing lipidperoxidation and the activity of some antioxidant enzymes.In conclusion, antioxidant compounds can only protect partially against the liver damage induced byGris, reducing oxidative stress, or acting on heme regulation.