RT Journal Article
SR Electronic
T1 A silybin-phospholipids complex prevents mitochondrial dysfunction in a rodent model of non-alcoholic steatohepatitis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.109.161612
DO 10.1124/jpet.109.161612
A1 Gaetano Serviddio
A1 Francesco Bellanti
A1 Anna Maria Giudetti
A1 Gabriele Vincenzo Gnoni
A1 Antonio Petrella
A1 Rosanna Tamborra
A1 Antonino Davide Romano
A1 Tiziana Rollo
A1 Gianluigi Vendemiale
A1 Emanuele Altomare
YR 2009
UL http://jpet.aspetjournals.org/content/early/2009/12/11/jpet.109.161612.abstract
AB Mitochondrial dysfunction and oxidative stress are determinant events in the pathogenesis of non-alcoholic steatohepatitis. Silybin has shown antioxidant, anti-inflammatory and antifibrotic effects in chronic liver disease. We aimed to study the effect of the silybin-phospholipids complex (SILIPHOS) on liver redox balance and mitochondrial function in a dietary model of NASH. To 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-choline deficient diet (MCD) and MCD + 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, 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 non-alcoholic steatohepatitis induced by MCD diet. The modifications of mitochondrial membrane fatty acid composition induced by 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 a preserved mitochondrial function.The American Society for Pharmacology and Experimental Therapeutics