title: Protective Effect of Tyrosol and S-Adenosylmethionine against Ethanol-Induced Oxidative Stress of Hepg2 Cells Involves Sirtuin 1, P53 and Erk1/2 Signaling.
abstract: 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.
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. paola.stiuso@unina2.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. marialibera.bagarolo@unina2.it.
authors.forename: Maria Libera
authors.initials: ML
authors.lastname: Bagarolo
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. concettapaola.Ilisso@unina2.it.
authors.forename: Concetta Paola
authors.initials: CP
authors.lastname: Ilisso
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. daniela.vanacore@unina2.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vanacore
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. elisa.martino@unina2.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martino
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. michele.caraglia@unina2.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. marina.porcelli@unina2.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Porcelli
authors.affiliation: Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy. giovanna.cacciapuoti@unina2.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cacciapuoti
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D020011:Protective Agents; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C011867:4-hydroxyphenylethanol; D000431:Ethanol; D012436:S-Adenosylmethionine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D056564:Sirtuin 1; D010626:Phenylethyl Alcohol
keywords: Hepg2; S-adenosylmethionine; Sirtuin 1; Tyrosol; ethanol