Abstract

The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property.

Autore Pugliese

• Siculella Luisa , Giudetti Anna Maria , Capobianco Loredana

Tutti gli autori

• Serviddio G , Bellanti F , Stanca E , Lunetti P , Blonda M , Tamborra R , Siculella L , Vendemiale G , Capobianco L , Giudetti AM

Titolo volume/Rivista

FREE RADICAL BIOLOGY & MEDICINE

Anno di pubblicazione

2014

ISSN

0891-5849

ISBN

Non Disponibile

Numero di citazioni Wos

29

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

32

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile