{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:15:58Z","timestamp":1786979758235,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the protective role of myricetin bulk and nanoforms, against reactive oxygen species (ROS)-induced oxidative stress caused by hydrogen peroxide and tertiary-butyl hydro peroxide in lymphocytes in vitro from healthy individuals and those from pre-cancerous patients suffering with monoclonal gammopathy of undetermined significance (MGUS). The change in intracellular reactive oxygen species was measured once cells were treated with myricetin bulk forms and nanoforms with and without either hydrogen peroxide or tertiary-butyl hydro peroxide co-supplementation. The direct and indirect antioxidant activity of myricetin was spectrofluometrically measured using the fluorescent dye 2\u2032,7\u2032-dichlorofluorescin diacetate and using the Comet assay, respectively. Hydrogen peroxide (50\u00a0\u00b5M) and tertiary-butyl hydro peroxide (300\u00a0\u00b5M) induced a higher level of reactive oxygen species-related DNA damage and strand breaks. Addition of myricetin nanoform (20\u00a0\u00b5M) and bulk (10\u00a0\u00b5M) form could, however, significantly prevent hydrogen peroxide- and tertiary-butyl hydro peroxide-induced oxidative imbalances and the nanoform was more effective. Glutathione levels were also quantified using a non-fluorescent dye. Results suggest that myricetin treatment had no significant effect on the cellular antioxidant enzyme, glutathione. The current study also investigates the effect of myricetin on the induction of double-strand breaks by staining the gamma-H2AX foci immunocytochemically. It was observed that myricetin does not induce double-strand breaks at basal levels rather demonstrated a protective effect.<\/jats:p>","DOI":"10.1007\/s00204-020-02688-4","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T01:02:45Z","timestamp":1582765365000},"page":"1229-1239","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["ROS-induced oxidative damage in lymphocytes ex vivo\/in vitro from healthy individuals and MGUS patients: protection by myricetin bulk and nanoforms"],"prefix":"10.1007","volume":"94","author":[{"given":"Shabana","family":"Akhtar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan","family":"Najafzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Isreb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendran C.","family":"Gopalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-0398","authenticated-orcid":false,"given":"Diana","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"issue":"10","key":"2688_CR1","doi-asserted-by":"publisher","first-page":"4563","DOI":"10.1096\/fj.14-254748","volume":"28","author":"D Anderson","year":"2014","unstructured":"Anderson D et al (2014) Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics. FASEB J 28(10):4563\u20134570","journal-title":"FASEB J"},{"key":"2688_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3389\/fgene.2015.00239","volume":"6","author":"A Azqueta","year":"2015","unstructured":"Azqueta A, Dusinska M (2015) The use of the comet assay for the evaluation of the genotoxicity of nanomaterials. Front Genet 6:239","journal-title":"Front Genet"},{"key":"2688_CR3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0006-291X(82)91237-2","volume":"106","author":"U Benatti","year":"1982","unstructured":"Benatti U, Morelli A, Damiani G, De Flora A (1982) A methemoglobin dependent and plasma-stimulated experimental model of oxidative hemolysis. Biochem Biophys Res Commun 106:183\u20131190","journal-title":"Biochem Biophys Res Commun"},{"key":"2688_CR4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.pathophys.2011.02.001","volume":"18","author":"S Bhattacharya","year":"2011","unstructured":"Bhattacharya S, Gachhui R, Sil PC (2011) Hepato-protective properties of Kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis. Pathophysiology 18:221\u2013234","journal-title":"Pathophysiology"},{"issue":"22","key":"2688_CR5","first-page":"7825","volume":"63","author":"AD Burdick","year":"2003","unstructured":"Burdick AD et al (2003) Benzo(%3cstrong%3e%3cem%3ea%3c\/em%3e%3c\/strong%3e)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells. Cancer Res 63(22):7825\u20137833","journal-title":"Cancer Res"},{"issue":"6","key":"2688_CR6","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.exer.2004.02.004","volume":"78","author":"K Chao-Wei Chen","year":"2004","unstructured":"Chao-Wei Chen K et al (2004) Platelet derived growth factor (PDGF)-induced reactive oxygen species in the lens epithelial cells: the redox signaling. Exp Eye Res 78(6):1057\u20131067","journal-title":"Exp Eye Res"},{"key":"2688_CR7","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1016\/j.fct.2011.06.066","volume":"49","author":"W Chen","year":"2011","unstructured":"Chen W, Li Y, Li J, Han Q, Ye L, Li A (2011) Myricetin affords protection against peroxynitrite-mediated DNA damage and hydroxyl radical formation. Food Chem Toxicol 49:2439\u20132444","journal-title":"Food Chem Toxicol"},{"key":"2688_CR8","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1179\/1351000211Y.0000000015","volume":"16","author":"V Chobot","year":"2011","unstructured":"Chobot V, Hadacek F (2011) Exploration of pro-oxidant and antioxidant activities of the flavonoid myricetin. Redox Rep 16:242\u2013247","journal-title":"Redox Rep"},{"issue":"3","key":"2688_CR9","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1385\/MB:26:3:249","volume":"26","author":"AR Collins","year":"2004","unstructured":"Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26(3):249\u2013261","journal-title":"Mol Biotechnol"},{"key":"2688_CR10","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/0005-2736(87)90245-8","volume":"899","author":"B Deuticke","year":"1987","unstructured":"Deuticke B, Heller KB, Haest WM (1987) Progressive oxidative membrane damage in erythrocytes after pulse treatment with tbutylhydroperoxide. Biochimica et Biophysica Acta 899:113\u2013124","journal-title":"Biochimica et Biophysica Acta"},{"issue":"23","key":"2688_CR11","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1182\/blood-2016-09-692954","volume":"128","author":"MV Dhodapkar","year":"2016","unstructured":"Dhodapkar MV (2016) MGUS to myeloma: a mysterious gammopathy of underexplored significance. Blood 128(23):2599\u20132606","journal-title":"Blood"},{"issue":"3","key":"2688_CR12","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S1383-5718(97)00107-1","volume":"393","author":"SJ Duthie","year":"1997","unstructured":"Duthie SJ et al (1997) Quercetin and myricetin protect against hydrogen peroxide-induced DNA damage (strand breaks and oxidised pyrimidines) in human lymphocytes. Mutat Res Genet Toxicol Environ Mutagenesis 393(3):223\u2013231","journal-title":"Mutat Res Genet Toxicol Environ Mutagenesis"},{"key":"2688_CR13","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/0006-2952(87)90724-6","volume":"36","author":"CG Fraga","year":"1987","unstructured":"Fraga CG, Martino VS, Ferraro GE, Coussio JD, Boveris A (1987) Flavonoids as antioxidants evaluated by in vitro and in situ liver chemiluminescence. Biochem Pharmacol 36:717\u2013720","journal-title":"Biochem Pharmacol"},{"issue":"11","key":"2688_CR14","doi-asserted-by":"publisher","first-page":"4348","DOI":"10.3390\/ijms11114348","volume":"11","author":"KA Kang","year":"2010","unstructured":"Kang KA et al (2010) Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K\/Akt and MAPK signaling pathways. Int J Mol Sci 11(11):4348\u20134360","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2688_CR15","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.exer.2007.04.003","volume":"85","author":"A Laabich","year":"2007","unstructured":"Laabich A et al (2007) Protective effects of myricetin and related flavonols against A2E and light mediated-cell death in bovine retinal primary cell culture. Exp Eye Res 85(1):154\u2013165","journal-title":"Exp Eye Res"},{"issue":"10","key":"2688_CR16","doi-asserted-by":"publisher","first-page":"3946","DOI":"10.1096\/fj.11-201194","volume":"26","author":"J Laubenthal","year":"2012","unstructured":"Laubenthal J et al (2012) Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring. FASEB J 26(10):3946\u20133956","journal-title":"FASEB J"},{"issue":"13\u201315","key":"2688_CR17","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1080\/15287394.2012.690326","volume":"75","author":"Z Magdolenova","year":"2012","unstructured":"Magdolenova Z et al (2012) Can standard genotoxicity tests be applied to nanoparticles? J Toxicol Environ Health Part A 75(13\u201315):800\u20138061","journal-title":"J Toxicol Environ Health Part A"},{"issue":"3","key":"2688_CR18","doi-asserted-by":"publisher","first-page":"233","DOI":"10.3109\/17435390.2013.773464","volume":"8","author":"Z Magdolenova","year":"2014","unstructured":"Magdolenova Z et al (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8(3):233\u2013278","journal-title":"Nanotoxicology"},{"key":"2688_CR19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.tox.2013.05.006","volume":"310","author":"N M\u00fcller","year":"2013","unstructured":"M\u00fcller N, Moreno-Villanueva M, Fischbach A, Kienh\u00f6fer J, Martello R, Dedon PC, Ullrich V, B\u00fcrkle A, Mangerich A (2013) An automated Fpg-based FADU method for the detection of oxidative DNA lesions and screening of antioxidants. Toxicoloy 310:15\u201321","journal-title":"Toxicoloy"},{"key":"2688_CR20","doi-asserted-by":"publisher","DOI":"10.1787\/9789264264885-en","volume-title":"Test No. 489: in vivo mammalian alkaline comet assay","author":"OECD","year":"2016","unstructured":"OECD (2016) Test No. 489: in vivo mammalian alkaline comet assay. OECD Publishing, Paris"},{"key":"2688_CR21","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1515\/znc-2009-9-1004","volume":"64","author":"KB Pandey","year":"2009","unstructured":"Pandey KB, Mishra N, Rizvi SI (2009) Myricetin may provide protection against oxidative stress in type 2 diabetic erythrocytes. Z Naturforsch C 64:626\u2013630","journal-title":"Z Naturforsch C"},{"issue":"7","key":"2688_CR22","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1093\/jn\/133.7.2184","volume":"133","author":"IW Peng","year":"2003","unstructured":"Peng IW, Kuo SM (2003) Research communication: flavonoid structure affects the inhibition of lipid peroxidation in Caco-2 intestinal cells at physiological concentrations. J Nutr 133(7):2184\u20132187","journal-title":"J Nutr"},{"key":"2688_CR23","first-page":"1645","volume":"60","author":"CL Perkins","year":"2000","unstructured":"Perkins CL, Fang G, Kim CN, Bhalla KN (2000) The role of Apaf-1, caspase- 9, and bid proteins in etoposide- or paclitaxel-induced mitochondrial events during apoptosis. Cancer Res 60:1645\u20131653","journal-title":"Cancer Res"},{"key":"2688_CR24","doi-asserted-by":"publisher","DOI":"10.4061\/2010\/920161","author":"M Podhorecka","year":"2010","unstructured":"Podhorecka M et al (2010) H2AX phosphorylation: its role in DNA damage response and cancer therapy. J Nucleic Acids. https:\/\/doi.org\/10.4061\/2010\/920161","journal-title":"J Nucleic Acids"},{"key":"2688_CR25","doi-asserted-by":"publisher","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","volume":"273","author":"EP Rogakou","year":"1998","unstructured":"Rogakou EP, Pilch DR, Orr AH, Ivanova BS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858\u20135868","journal-title":"J Biol Chem"},{"issue":"5","key":"2688_CR26","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1083\/jcb.146.5.905","volume":"146","author":"EP Rogakou","year":"1999","unstructured":"Rogakou EP et al (1999) Megabase chromatin domains involved in DNA double-stranded breaks in vivo. J Cell Biol 146(5):905\u2013916","journal-title":"J Cell Biol"},{"issue":"2","key":"2688_CR27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.pathophys.2012.05.001","volume":"19","author":"A Roy","year":"2012","unstructured":"Roy A, Sil PC (2012) Tertiary butyl hydroperoxide induced oxidative damage in mice erythrocytes: protection by taurine. Pathophysiology 19(2):137\u2013148","journal-title":"Pathophysiology"},{"key":"2688_CR28","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1016\/j.tiv.2010.05.014","volume":"24","author":"MK Sarkar","year":"2010","unstructured":"Sarkar MK, Sil PC (2010) Prevention of tertiary butyl hydroperoxide induced oxidative impairment and cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri. Toxicology In Vitro 24:1711\u20131719","journal-title":"Toxicology In Vitro"},{"issue":"8","key":"2688_CR29","doi-asserted-by":"publisher","first-page":"682","DOI":"10.3109\/09553001003734543","volume":"86","author":"TE Schmid","year":"2010","unstructured":"Schmid TE et al (2010) Differences in the kinetics of \u03b3-H2AX fluorescence decay after exposure to low and high LET radiation. Int J Radiat Biol 86(8):682\u2013691","journal-title":"Int J Radiat Biol"},{"issue":"2","key":"2688_CR30","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/nu8020090","volume":"8","author":"DK Semwal","year":"2016","unstructured":"Semwal DK et al (2016) Myricetin: a dietary molecule with diverse biological activities. Nutrients 8(2):90","journal-title":"Nutrients"},{"issue":"2","key":"2688_CR31","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1002\/jnr.21476","volume":"86","author":"Y Shimmyo","year":"2008","unstructured":"Shimmyo Y et al (2008) Multifunction of myricetin on A\u03b2: neuroprotection via a conformational change of A\u03b2 and reduction of A\u03b2 via the interference of secretases. J Neurosci Res 86(2):368\u2013377","journal-title":"J Neurosci Res"},{"issue":"1","key":"2688_CR32","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/0014-4827(88)90265-0","volume":"175","author":"NP Singh","year":"1988","unstructured":"Singh NP et al (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184\u2013191","journal-title":"Exp Cell Res"},{"key":"2688_CR33","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/S0891-5849(01)00593-7","volume":"31","author":"W Slikker","year":"2001","unstructured":"Slikker W, Desai VG, Duhart H, Feuers R, Imam SZ (2001) Hypothermia enhances bcl-2 expression and protects against oxidative stress induced cell death in Chinese hamster ovary cells. Free Radic Biol Med 31:405\u2013411","journal-title":"Free Radic Biol Med"},{"issue":"9","key":"2688_CR34","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/cyto.a.20426","volume":"71","author":"T Tanaka","year":"2007","unstructured":"Tanaka T, Huang X, Halicka HD et al (2007) Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents. Cytometry Part A 71(9):648\u2013661","journal-title":"Cytometry Part A"},{"key":"2688_CR35","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J","volume":"35","author":"RR Tice","year":"2000","unstructured":"Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel\/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206\u2013221","journal-title":"Environ Mol Mutagen"},{"issue":"4","key":"2688_CR36","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/S0891-5849(01)00616-5","volume":"31","author":"G Varbiro","year":"2001","unstructured":"Varbiro G et al (2001) Direct effect of Taxol on free radical formation and mitochondrial permeability transition. Free Rad Biol Med 31(4):548\u2013558","journal-title":"Free Rad Biol Med"},{"issue":"22","key":"2688_CR37","doi-asserted-by":"publisher","first-page":"12871","DOI":"10.1073\/pnas.2135498100","volume":"100","author":"MM Vilenchik","year":"2003","unstructured":"Vilenchik MM, Knudson AG (2003) Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA 100(22):12871\u201312876","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"2688_CR38","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.etap.2009.08.007","volume":"29","author":"ZH Wang","year":"2010","unstructured":"Wang ZH et al (2010) Myricetin suppresses oxidative stress-induced cell damage via both direct and indirect antioxidant action. Environ Toxicol Pharmacol 29(1):12\u201318","journal-title":"Environ Toxicol Pharmacol"},{"key":"2688_CR39","first-page":"577","volume":"44","author":"LB Zavodnik","year":"1988","unstructured":"Zavodnik LB, Zavodnik IB, Niekurzak A, Szosland K, Bryszewska M (1988) Activation of red blood cell glutathione peroxidase and morphological transformation of erythrocytes under the action of tert-butyl hydroperoxide. Biochem Mol Biol Int 44:577\u2013588","journal-title":"Biochem Mol Biol Int"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-020-02688-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-020-02688-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-020-02688-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T19:14:31Z","timestamp":1614280471000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-020-02688-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,27]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["2688"],"URL":"https:\/\/doi.org\/10.1007\/s00204-020-02688-4","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,27]]},"assertion":[{"value":"14 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}