Protection of human HepG2 cells against oxidative stress by the flavonoid epicatechin

Flavanols, such as epicatechin (EC), constitute an important part of the human diet; they can be found in green tea, grapes and cocoa and possess different biological activities such as antioxidant, anti‐inflammatory and anticarcinogenic. This study investigated the potential chemo‐protective effect of EC against oxidative stress induced by tert‐butylhydroperoxide (t‐BOOH) on human HepG2 cells. Cell viability by lactate dehydrogenase assay and markers of oxidative status: reduced glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), glutathione peroxidase (GPx) and glutathione reductase (GR) were evaluated. Pretreatment of cells with EC for 20 h prevented the enhanced cell damage and GPx and GR activities as well as the decrease in GSH induced by t‐BOOH. The increased ROS generation induced by t‐BOOH was also partly prevented by a pretreatment for 20 h with EC. In addition, pretreatment of cells with EC for 20 h recovered the t‐BOOH‐induced MDA concentration to control values. A pretreatment for 2 h with EC did not reduce cell damage but partly recovered GSH, reduced ROS levels and muffled the increase of GPx and GR after exposure to t‐BOOH. Treatment of HepG2 cells with concentrations of EC in the micromolar range confers a significant protection against oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.

[1]  L. Goya,et al.  Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cells. , 2010, The Journal of nutritional biochemistry.

[2]  M. Angeles Martín,et al.  Time-course regulation of survival pathways by epicatechin on HepG2 cells. , 2009, The Journal of nutritional biochemistry.

[3]  Y. Boo,et al.  Effect of green tea and (‐)‐epigallocatechin gallate on ethanol‐induced toxicity in HepG2 cells , 2008, Phytotherapy research : PTR.

[4]  F. Ciardiello,et al.  Chronic inflammation and oxidative stress in human carcinogenesis , 2007, International journal of cancer.

[5]  L. Klotz,et al.  Protein modification elicited by oxidized low-density lipoprotein (LDL) in endothelial cells: protection by (-)-epicatechin. , 2007, Free radical biology & medicine.

[6]  L. Goya,et al.  Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. , 2007, Journal of agricultural and food chemistry.

[7]  R. Mateos,et al.  Chromatographic and electrophoretic methods for the analysis of biomarkers of oxidative damage to macromolecules (DNA, lipids, and proteins). , 2007, Journal of separation science.

[8]  L. Goya,et al.  Effect of the olive oil phenol hydroxytyrosol on human hepatoma HepG2 cells , 2007, European journal of nutrition.

[9]  T. Hashimoto,et al.  Bioavailable flavonoids to suppress the formation of 8-OHdG in HepG2 cells. , 2006, Archives of biochemistry and biophysics.

[10]  L. Goya,et al.  Uptake and metabolism of hydroxycinnamic acids (chlorogenic, caffeic, and ferulic acids) by HepG2 cells as a model of the human liver. , 2006, Journal of agricultural and food chemistry.

[11]  D. Poelman,et al.  In-vitro effects of polyphenols from cocoa and &bgr;-sitosterol on the growth of human prostate cancer and normal cells , 2006, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[12]  L. Goya,et al.  Quercetin protects human hepatoma HepG2 against oxidative stress induced by tert-butyl hydroperoxide. , 2006, Toxicology and applied pharmacology.

[13]  P. O'Brien,et al.  Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. , 2006, Free radical biology & medicine.

[14]  J. Schellens,et al.  Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines. , 2006, Toxicology and applied pharmacology.

[15]  L. Goya,et al.  Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2) , 2006, European journal of nutrition.

[16]  L. Goya,et al.  Metabolism of the olive oil phenols hydroxytyrosol, tyrosol, and hydroxytyrosyl acetate by human hepatoma HepG2 cells. , 2005, Journal of agricultural and food chemistry.

[17]  F. Pérez-Cano,et al.  Flavonoids from Theobroma cacao down-regulate inflammatory mediators. , 2005, Journal of agricultural and food chemistry.

[18]  V. Fogliano,et al.  Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo , 2005, Gut.

[19]  K. Kondo,et al.  In Vitro Antioxidative Activity of (−)-Epicatechin Glucuronide Metabolites Present in Human and Rat Plasma , 2004, Free radical research.

[20]  S. Azam,et al.  Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[21]  L. Goya,et al.  Determination of malondialdehyde by liquid chromatography as the 2,4-dinitrophenylhydrazone derivative: a marker for oxidative stress in cell cultures of human hepatoma HepG2. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[22]  Liliana Jiménez,et al.  Polyphenols: food sources and bioavailability. , 2004, The American journal of clinical nutrition.

[23]  R. Schulte‐Hermann,et al.  Enhancement of Glutathione and γ-Glutamylcysteine Synthetase, the Rate Limiting Enzyme of Glutathione Synthesis, by Chemoprotective Plant-Derived Food and Beverage Components in the Human Hepatoma Cell Line HepG2 , 2003, Nutrition and cancer.

[24]  J. Kanner,et al.  Antioxidant and prooxidant effects of phenolics on pancreatic β-cells in vitro , 2002 .

[25]  Hongli Jiao,et al.  Tea catechins protect against lead-induced cytotoxicity, lipid peroxidation, and membrane fluidity in HepG2 cells. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  S. Lazarus,et al.  Inhibitory Effects of Cocoa Flavanols and Procyanidin Oligomers on Free Radical-Induced Erythrocyte Hemolysis , 2002, Experimental biology and medicine.

[27]  S. Lazarus,et al.  Chocolate consumption and platelet function. , 2002, JAMA.

[28]  H. Inui,et al.  Effects of epigallocatechin 3-O-gallate on cellular antioxidative system in HepG2 cells. , 2002, Journal of nutritional science and vitaminology.

[29]  M. Natsume,et al.  In vivo comparison of the bioavailability of (+)-catechin, (-)-epicatechin and their mixture in orally administered rats. , 2001, The Journal of nutrition.

[30]  E. van Nood,et al.  Flavonoids: a review of probable mechanisms of action and potential applications. , 2001, The American journal of clinical nutrition.

[31]  P. O'Brien,et al.  Catechin metabolism: glutathione conjugate formation catalyzed by tyrosinase, peroxidase, and cytochrome p450. , 2001, Chemical research in toxicology.

[32]  C. Fraga,et al.  Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. , 2000, The Journal of nutrition.

[33]  J. Kyle,et al.  Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants , 2000, Nutrition Research Reviews.

[34]  C. Rice-Evans,et al.  The small intestine can both absorb and glucuronidate luminal flavonoids , 1999, FEBS letters.

[35]  M. Hill,et al.  Bacterial fermentation of complex carbohydrate in the human colon. , 1995, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[36]  J. Kanner,et al.  Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. , 2002, Journal of agricultural and food chemistry.