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Int. J. Mol. Sci. 2016, 17(5), 622;

Protective Effect of Tyrosol and S-Adenosylmethionine against Ethanol-Induced Oxidative Stress of Hepg2 Cells Involves Sirtuin 1, P53 and Erk1/2 Signaling

Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Ashok K. Singh
Received: 24 February 2016 / Revised: 11 April 2016 / Accepted: 12 April 2016 / Published: 26 April 2016
(This article belongs to the Special Issue Alcoholism: Molecular Mechanisms and Treatment Strategies)
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Oxidative stress plays a major role in ethanol-induced liver damage, and agents with antioxidant properties are promising as therapeutic opportunities in alcoholic liver disease. In the present work, we investigated the effect of S-adenosylmethionine (AdoMet), Tyrosol (Tyr), and their combination on HepG2 cells exposed to ethanol exploring the potential molecular mechanisms. We exposed HepG2 cells to 1 M ethanol for 4 and 48 h; thereafter, we recorded a decreased cell viability, increase of intracellular reactive oxygen species (ROS) and lipid accumulation, and the release into culture medium of markers of liver disease such as triacylglycerol, cholesterol, transaminases, albumin, ferritin, and homocysteine. On the other hand, AdoMet and Tyrosol were able to attenuate or antagonize these adverse changes induced by acute exposure to ethanol. The protective effects were paralleled by increased Sirtuin 1 protein expression and nuclear translocation and increased ERK1/2 phosphorylation that were both responsible for the protection of cells from apoptosis. Moreover, AdoMet increased p53 and p21 expression, while Tyrosol reduced p21 expression and enhanced the expression of uncleaved caspase 3 and 9, suggesting that its protective effect may be related to the inhibition of the apoptotic machinery. Altogether, our data show that AdoMet and Tyrosol exert beneficial effects in ethanol-induced oxidative stress in HepG2 cells and provide a rationale for their potential use in combination in the prevention of ethanol-induced liver damage. View Full-Text
Keywords: Tyrosol; S-adenosylmethionine; Sirtuin 1; Hepg2; ethanol Tyrosol; S-adenosylmethionine; Sirtuin 1; Hepg2; ethanol

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Stiuso, P.; Bagarolo, M.L.; Ilisso, C.P.; Vanacore, D.; Martino, E.; Caraglia, M.; Porcelli, M.; Cacciapuoti, G. Protective Effect of Tyrosol and S-Adenosylmethionine against Ethanol-Induced Oxidative Stress of Hepg2 Cells Involves Sirtuin 1, P53 and Erk1/2 Signaling. Int. J. Mol. Sci. 2016, 17, 622.

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