Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis

Gaetano Serviddio, Francesco Bellanti, Eleonora Stanca, Paola Lunetti, Maria Blonda, Rosanna Tamborra, Luisa Siculella, Gianluigi Vendemiale, Loredana Capobianco, Anna Maria Giudetti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalFree Radical Biology and Medicine
Volume73
DOIs
Publication statusPublished - 2014

Keywords

  • Citrate carrier
  • Free radicals
  • Lipogenic enzymes
  • Mitochondrial biogenesis
  • Peroxisome proliferator-activated receptor coactivator-1α
  • Secondary biliary cirrhosis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

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