{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:08:21Z","timestamp":1790068101947,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T00:00:00Z","timestamp":1570579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007652","name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria","doi-asserted-by":"publisher","award":["RTA2015-00005-C02-02"],"award-info":[{"award-number":["RTA2015-00005-C02-02"]}],"id":[{"id":"10.13039\/100007652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["RTA2015-00005-C02-02"],"award-info":[{"award-number":["RTA2015-00005-C02-02"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006251","name":"Universit\u00e9 de Bordeaux","doi-asserted-by":"publisher","award":["ANR-11-INBS-0010"],"award-info":[{"award-number":["ANR-11-INBS-0010"]}],"id":[{"id":"10.13039\/501100006251","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The reduction of sulfur dioxide in wine is a consumer\u2019s demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant\/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 \u03bcg\/mL after 24 h, and 40 \u00b5g\/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.<\/jats:p>","DOI":"10.3390\/antiox8100467","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T11:25:57Z","timestamp":1570620357000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-3694","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Medrano-Padial","sequence":"first","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, C\/Profesor Garc\u00eda Gonz\u00e1lez n\u00b02, Universidad de Sevilla, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Puerto","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, C\/Profesor Garc\u00eda Gonz\u00e1lez n\u00b02, Universidad de Sevilla, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-199X","authenticated-orcid":false,"given":"F. Javier","family":"Moreno","sequence":"additional","affiliation":[{"name":"Area of Cellular Biology, Faculty of Biology, Avda. Reina Mercedes s\/n, Universidad de Sevilla, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-8697","authenticated-orcid":false,"given":"Tristan","family":"Richard","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences Pharmaceutiques, Unit\u00e9 de Recherche OEnologie EA 4577, USC 1366 INRA, Equipe Mol\u00e9cules d\u2019Int\u00e9r\u00eat Biologique (Gesvab) - Institut des Sciences de la Vigne et du Vin, Universit\u00e9 de Bordeaux, CS 50008 - 210, Chemin de Leysotte, 33882 Villenave d\u2019Ornon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Cantos-Villar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n y Formaci\u00f3n Agraria y Pesquera (IFAPA), Centro Rancho de la Merced, Consejer\u00eda de Agricultura, Ganader\u00eda, Pesca y Desarrollo Sostenible (Junta de Andaluc\u00eda). Ca\u00f1ada de la Loba, 11471 Jerez de la Frontera, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-1942","authenticated-orcid":false,"given":"Silvia","family":"Pichardo","sequence":"additional","affiliation":[{"name":"Area of Toxicology, Faculty of Pharmacy, C\/Profesor Garc\u00eda Gonz\u00e1lez n\u00b02, Universidad de Sevilla, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tifs.2014.11.004","article-title":"Demonstrating the efficiency of sulphur dioxide replacements in wine: A parameter review","volume":"42","author":"Guerrero","year":"2015","journal-title":"Food. Sci. Technol."},{"key":"ref_2","unstructured":"EC, European Parliament and of the Council (2006). Directive 2006\/52\/EC of the European Parliament and of the Council of 5 July 2006 amending directive 95\/2\/EC on food additives other than colours and sweeteners and Directive 94\/35\/EC on sweeteners for use in foodstuffs. Off. J. Eur. Union, 204, 10\u201322."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.fpsl.2018.10.008","article-title":"Grapevine-shoot stilbene extract as a preservative in white wine","volume":"18","author":"Cruz","year":"2018","journal-title":"Food Packag. Shelf Life"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00217-011-1614-6","article-title":"Chemical and physical methodologies for the replacement\/reduction of sulfur dioxide use during winemaking: Review of their potentialities and limitations","volume":"234","author":"Santos","year":"2012","journal-title":"Eur. Food Res. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.jff.2015.06.018","article-title":"Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects\u2014A review","volume":"18","author":"Shahidi","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.lwt.2012.04.006","article-title":"Grape stem extracts Polyphenolic content and assessment of their in vitro antioxidant properties","volume":"48","author":"Anastasiadi","year":"2012","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1021\/acs.jafc.7b01254","article-title":"Antioxidant and Cytoprotective Activities of Grapevine Stilbenes","volume":"65","author":"Biais","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1271\/bbb.90213","article-title":"Potent Antioxidative Activity of Vineatrol\u00ae30 Grapevine-shoot Extract","volume":"73","author":"Ullmann","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.indcrop.2014.10.016","article-title":"Valorization of grape stems","volume":"63","author":"Raposo","year":"2015","journal-title":"Ind. Crop. Prod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.foodchem.2015.11.102","article-title":"Grapevine-shoot stilbene extract as a preservative in red wine","volume":"197","author":"Raposo","year":"2016","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.foodchem.2017.09.111","article-title":"Sulfur free red wines through the use of grapevine shoots: Impact on the wine quality","volume":"243","author":"Raposo","year":"2018","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"EFSA (European Food Safety Authority) (2012). Guidance for submission for food additive evaluations. EFSA J., 10, 2760.","DOI":"10.2903\/j.efsa.2012.2760"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/87559129.2016.1175010","article-title":"New advances in active packaging incorporated with essential oils or their main components for food preservation","volume":"33","author":"Maisanaba","year":"2017","journal-title":"Food Rev. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2478\/v10004-007-0020-8","article-title":"Evaluation of resveratrol and piceatannol cytotoxicity in macrophages, T cells, and skin cells","volume":"58","author":"Radkar","year":"2007","journal-title":"Arhiv za Higijenu Rada i Toksikologiju"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1080\/1042819021000015952","article-title":"Comparative Antiproliferative and Apoptotic Effects of resveratrol, \u03b5-viniferin and vine-shots Derived Polyphenols (Vineatrols) on Chronic B Lymphocytic Leukemia Cells and Normal Human Lymphocytes","volume":"43","author":"Billard","year":"2002","journal-title":"Leuk. Lymphoma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/mnfr.200700185","article-title":"Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells","volume":"52","author":"Marel","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/j.biochi.2008.06.006","article-title":"Antiproliferative activities of resveratrol and related compounds in human hepatocyte derived HepG2 cells are associated with biochemical cell disturbance revealed by fluorescence analyses","volume":"90","author":"Colin","year":"2008","journal-title":"Biochimie"},{"key":"ref_18","first-page":"635","article-title":"Wine, resveratrol and health: A review","volume":"4","author":"Guerrero","year":"2009","journal-title":"Nat. Prod. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1016\/j.bmc.2011.04.001","article-title":"Protective effect of \u03b5-viniferin on b-amyloid peptide aggregation investigated by electrospray ionization mass spectrometry","volume":"19","author":"Richard","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.biochi.2011.11.001","article-title":"Antioxidant effects of resveratrol and other stilbene derivatives on oxidative stress and NO bioavailability: Potential benefits to cardiovascular diseases","volume":"94","author":"Frombaum","year":"2012","journal-title":"Biochimie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0027-5107(01)00073-2","article-title":"Role of plant polyphenols in genomic stability","volume":"475","author":"Ferguson","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_22","first-page":"735","article-title":"A comparative evaluation of antioxidant and anticancer activity of essential oil from Origanum onites (Lamiaceae) and its two major phenolic components","volume":"35","author":"Ozkan","year":"2011","journal-title":"Turk. J. Biol."},{"key":"ref_23","first-page":"1566","article-title":"Biochemical and pathological toxic effects induced by the cyanotoxin Cylindrospermopsin on the human cell line Caco-2","volume":"49","author":"Pichardo","year":"2012","journal-title":"Water Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s10340-018-0956-2","article-title":"Stilbenes from grapevine root: A promising natural insecticide against Leptinotarsa decemlineata","volume":"91","author":"Gabaston","year":"2018","journal-title":"J. Pest Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.indcrop.2016.09.055","article-title":"Grapevine cane\u2019s waste is a source of bioactive stilbenes","volume":"94","author":"Guerrero","year":"2016","journal-title":"Ind. Crop. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/BF01666038","article-title":"A simple quantitative procedure using monolayer culture for cytotoxicity assays","volume":"9","author":"Borenfreud","year":"1984","journal-title":"J. Tissue Cult. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/BF00249595","article-title":"Neutral red (NR) assay for cell viability and xenobiotic-induced cytotoxicity in primary cultures of human and rat hepatocytes","volume":"6","author":"Zhang","year":"1990","journal-title":"Cell Biol. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0960-894X(01)81162-8","article-title":"5-((3-carboxyphenyl)-3-(4,5 dimethilthiazolyl)-3-(4- sulfophenyl) tetrazolium, inner salt (MTS) and related analogs of 2- (4,5- dimethylthiazolyl)- 2,5- diphenylterazolium bromide (MTT) reducing to purple water soluble formazan as cell viability indicators","volume":"1","author":"Baltrop","year":"1991","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/tox.22679","article-title":"Cytotoxic and morphological effects of microcystin-LR, cylindrospermopsin, and their combinations on the human hepatic cell line HepG2","volume":"34","author":"Pichardo","year":"2019","journal-title":"Environ. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8768","DOI":"10.1021\/jf0512003","article-title":"Hydrogen Peroxide Induced Oxidative Stress Damage and Antioxidant Enzyme Response in Caco-2 Human Colon Cells","volume":"53","author":"Wijeratne","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1021\/jf4010252","article-title":"Vitis vinifera canes, a new source of antifungal compounds against Plasmopara viticola, Erysiphe necator, and Botrytis cinerea","volume":"61","author":"Schnee","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1002\/ijc.24264","article-title":"Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells","volume":"124","author":"Colin","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1590\/1678-4685-gmb-2016-0214","article-title":"Cytotoxicity and genotoxicity of stilbene derivatives in CHO-K1 and HepG2 cell lines","volume":"40","author":"Mizuno","year":"2017","journal-title":"Genet. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1002\/ptr.5443","article-title":"The Resveratrol Tetramer r-Viniferin Induces a Cell Cycle Arrest Followed by Apoptosis in the Prostate Cancer Cell Line LNCaP","volume":"29","author":"Empl","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.btre.2017.11.004","article-title":"Cancer cell lines involving cancer stem cell populations respond to oxidative stress","volume":"17","author":"Yilmazer","year":"2018","journal-title":"Biotechnol. Rep."},{"key":"ref_37","first-page":"1","article-title":"Anticancer Activity of Stilbene-Based Derivatives","volume":"12","author":"Ammazzalorso","year":"2017","journal-title":"Chem. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.yexcr.2018.06.031","article-title":"Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence in cancer cells","volume":"370","author":"Ji","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.lfs.2018.06.028","article-title":"Resveratrol: An overview of its anti-cancer mechanisms","volume":"207","author":"Elshaer","year":"2018","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13046-018-0737-z","article-title":"Lipid accumulation in human breast cancer cells injured by iron depletors","volume":"37","author":"Taverna","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/aob\/mcf118","article-title":"Antioxidants, oxidative damage and oxygen deprivation stress: A review","volume":"91","author":"Blokhina","year":"2003","journal-title":"Ann. Bot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.tiv.2015.02.006","article-title":"In vitro pro-oxidant\/antioxidant role of carvacrol, thymol and their mixture in the intestinal Caco-2 cell line","volume":"29","author":"Puerto","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21154","DOI":"10.3390\/molecules191221154","article-title":"In vitro and in vivo evaluation of the antioxidant and prooxidant activity of phenolic compounds obtained from grape (Vitis vinifera) pomace","volume":"19","author":"Cotoras","year":"2014","journal-title":"Molecules"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.3892\/mmr.2015.4216","article-title":"Polyphenolic composition of grape stem extracts affects antioxidant activity in endothelial and muscle cells","volume":"12","author":"Goutzourelas","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3892\/ijmm.2015.2246","article-title":"Grape pomace extract exerts antioxidant effects through an increase in GCS levels and GST activity in muscle and endothelial cells","volume":"36","author":"Goutzourelas","year":"2015","journal-title":"Int. J. Mol. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/8\/10\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:28:36Z","timestamp":1760189316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/8\/10\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,9]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["antiox8100467"],"URL":"https:\/\/doi.org\/10.3390\/antiox8100467","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,9]]}}}