A silybin-phospholipid complex prevents mitochondrial dysfunction in a rodent model of nonalcoholic steatohepatitis

Gaetano Serviddio, Francesco Bellanti, Anna Maria Giudetti, Gabriele Vincenzo Gnoni, Antonio Petrella, Rosanna Tamborra, Antonino Davide Romano, Tiziana Rollo, Gianluigi Vendemiale, Emanuele Altomare

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Abstract

Mitochondrial dysfunction and oxidative stress are determinant events in the pathogenesis of nonalcoholic steatohepatitis. Silybin has shown antioxidant, anti-inflammatory, and antifibrotic effects in chronic liver disease. We aimed to study the effect of the silybin-phospholipid complex (SILIPHOS) on liver redox balance and mitochondrial function in a dietary model of nonalcoholic steatohepatitis. To accomplish this, glutathione oxidation, mitochondrial oxygen uptake, proton leak, ATP homeostasis, and H2O2 production rate were evaluated in isolated liver mitochondria from rats fed a methionine- and cholinedeficient (MCD) diet and the MCD diet plus SILIPHOS for 7 and 14 weeks. Oxidative proteins, hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and mitochondrial membrane lipid composition were also measured. Treatment with SILIPHOS limited glutathione depletion and mitochondrial H2O2 production. Moreover, SILIPHOS preserved mitochondrial bioenergetics and prevented mitochondrial proton leak and ATP reduction. Finally, SILIPHOS limited the formation of HNE- and MDA-protein adducts. In conclusion, SILIPHOS is effective in preventing severe oxidative stress and preserving hepatic mitochondrial bioenergetics in nonalcoholic steatohepatitis induced by the MCD diet. The modifications of mitochondrial membrane fatty acid composition induced by the MCD diet are partially prevented by SILIPHOS, conferring anti-inflammatory and antifibrotic effects. The increased vulnerability of lipid membranes to oxidative damage is limited by SILIPHOS through preserved mitochondrial function.

Original languageEnglish
Pages (from-to)922-932
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume332
Issue number3
DOIs
Publication statusPublished - Mar 2010

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Serviddio, G., Bellanti, F., Giudetti, A. M., Gnoni, G. V., Petrella, A., Tamborra, R., Romano, A. D., Rollo, T., Vendemiale, G., & Altomare, E. (2010). A silybin-phospholipid complex prevents mitochondrial dysfunction in a rodent model of nonalcoholic steatohepatitis. Journal of Pharmacology and Experimental Therapeutics, 332(3), 922-932. https://doi.org/10.1124/jpet.109.161612