PT  - JOURNAL ARTICLE
AU  - Gaetano Serviddio
AU  - Francesco Bellanti
AU  - Anna Maria Giudetti
AU  - Gabriele Vincenzo Gnoni
AU  - Antonio Petrella
AU  - Rosanna Tamborra
AU  - Antonino Davide Romano
AU  - Tiziana Rollo
AU  - Gianluigi Vendemiale
AU  - Emanuele Altomare
TI  - A Silybin-Phospholipid Complex Prevents Mitochondrial Dysfunction in a Rodent Model of Nonalcoholic Steatohepatitis
AID  - 10.1124/jpet.109.161612
DP  - 2010 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 922--932
VI  - 332
IP  - 3
4099  - http://jpet.aspetjournals.org/content/332/3/922.short
4100  - http://jpet.aspetjournals.org/content/332/3/922.full
SO  - J Pharmacol Exp Ther2010 Mar 01; 332
AB  - 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 choline-deficient (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.Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics