{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:15:10Z","timestamp":1787235310735,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/1-168-01\/503-11-001"],"award-info":[{"award-number":["503\/1-168-01\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Life"],"abstract":"<jats:p>Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin is an effective antioxidant, which protects against KIO3-induced LPO in the thyroid. This study aimed to compare the protective effects of melatonin, used in the highest achievable in vitro concentration, against KIO3-induced oxidative damage to membrane lipids in various porcine tissues (thyroid, ovary, liver, kidney, brain, spleen, and small intestine). Homogenates were incubated in the presence of KIO3 (20; 15; 10; 7.5; 5.0; 0.0 mM) without\/with melatonin (5 mM). The malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased the LPO in all examined tissues; in the thyroid, the damaging effect of KIO3 (10; and 7.5 mM) was lower than in other tissues and was not observed for the lowest concentration of 5 mM. Melatonin reduced LPO induced by KIO3 (10, 7.5, and 5 mM) in all tissues, and in the thyroid it was also protective against as high a concentration of KIO3 as 15 mM; the LPO level resulting from KIO3 + melatonin treatment was lower in the thyroid than in other tissues. In conclusion, the thyroid is less sensitive tothe pro-oxidative effects of KIO3 compared to other tissues. The strongest protective effect of melatonin was observed in the thyroid, but beneficial effects were significant also in other tissues. Melatonin should be considered to avoid the potential damaging effects of iodine compounds applied in iodine prophylaxis.<\/jats:p>","DOI":"10.3390\/life11060592","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T13:29:58Z","timestamp":1624282198000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid\u2014Comparison to Other Tissues"],"prefix":"10.3390","volume":"11","author":[{"given":"Paulina","family":"Iwan","sequence":"first","affiliation":[{"name":"Department of Oncological Endocrinology, Medical University of Lodz, 7\/9 Zeligowski St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-6228","authenticated-orcid":false,"given":"Jan","family":"Stepniak","sequence":"additional","affiliation":[{"name":"Department of Oncological Endocrinology, Medical University of Lodz, 7\/9 Zeligowski St., 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-5669","authenticated-orcid":false,"given":"Malgorzata","family":"Karbownik-Lewinska","sequence":"additional","affiliation":[{"name":"Department of Oncological Endocrinology, Medical University of Lodz, 7\/9 Zeligowski St., 90-752 Lodz, Poland"},{"name":"Polish Mother\u2019s Memorial Hospital\u2014Research Institute, 281\/289 Rzgowska St., 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1002\/med.21592","article-title":"The mechanism(s) of action of antioxidants: From scavenging reactive oxygen\/nitrogen species to redox signaling and the generation of bioactive secondary metabolites","volume":"39","author":"Hunyadi","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5080843","DOI":"10.1155\/2019\/5080843","article-title":"Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis","volume":"2019","author":"Su","year":"2019","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejmech.2015.04.040","article-title":"The role of antioxidants in the chemistry of oxidative stress: A review","volume":"97","author":"Pisoschi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2020.02.027","article-title":"Lipid peroxidation and ferroptosis: The role of GSH and GPx4","volume":"152","author":"Ursini","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1756-6614-5-25","article-title":"Oxidative damage to macromolecules in the thyroid\u2014Experimental evidence","volume":"5","year":"2012","journal-title":"Thyroid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.mce.2017.01.038","article-title":"Thyroid hormone biosynthesis and release","volume":"458","author":"Carvalho","year":"2017","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1210\/endo.141.2.7291","article-title":"Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress","volume":"141","author":"Vitale","year":"2000","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1210\/er.2012-1036","article-title":"The Na+\/I- symporter (NIS): Mechanism and medical impact","volume":"35","author":"Portulano","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1530\/eje.0.1410443","article-title":"Sodium\/iodide symporter: A key transport system in thyroid cancer cell metabolism","volume":"141","author":"Filetti","year":"1999","journal-title":"Eur. J. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1210\/er.2001-0029","article-title":"The sodium\/iodide Symporter (NIS): Characterization, regulation, and medical significance","volume":"24","author":"Paroder","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_13","unstructured":"Southern, A.P., and Jwayyed, S. (2021, April 11). Iodine Toxicity. StatPearls. Available online: https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/40905."},{"key":"ref_14","unstructured":"Shahid, M.A., Ashraf, M.A., and Sharma, S. (2020, May 18). Physiology, Thyroid Hormone. StatPearls. Available online: https:\/\/www.statpearls.com\/ArticleLibrary\/viewarticle\/30145."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S2213-8587(14)70225-6","article-title":"Iodine deficiency and thyroid disorders","volume":"3","author":"Zimmermann","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1007\/s13197-018-3277-9","article-title":"Effect of iodized salt on organoleptic properties of processed foods: A systematic review","volume":"55","author":"Blankenship","year":"2018","journal-title":"J. Food Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtemb.2015.04.005","article-title":"Analysis of potassium iodate reduction in tissue homogenates using high performance liquid chromatography-inductively coupled plasma-mass spectrometry","volume":"32","author":"Cao","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1756-6614-6-10","article-title":"Potassium iodide, but not potassium iodate, as a potential protective agent against oxidative damage to membrane lipids in porcine thyroid","volume":"6","author":"Milczarek","year":"2013","journal-title":"Thyroid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00394-014-0797-6","article-title":"Protective effect of KI in mtDNA in porcine thyroid: Comparison with KIO3 and nDNA","volume":"54","author":"Stepniak","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_20","first-page":"1","article-title":"Melatonin reduces high levels of lipid peroxidation induced by potassium iodate in porcine thyroid","volume":"17","author":"Iwan","year":"2019","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_21","first-page":"101","article-title":"Indole-3-propionic acid reduces lipid peroxidation induced by potassium iodate in porcine thyroid","volume":"13","author":"Iwan","year":"2020","journal-title":"Interdiscip. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Iwan, P., Stepniak, J., and Karbownik-Lewinska, M. (2021). Cumulative protective effect of melatonin and indole-3-propionic acid against KIO3-induced oxidative damage to membrane lipids in porcine thyroid homogenates. Toxics, 9.","DOI":"10.3390\/toxics9050089"},{"key":"ref_23","first-page":"6","article-title":"Iodine content of thyroid tissue in the Styrian population","volume":"20","author":"Tiran","year":"1993","journal-title":"Acta Med. Austriaca"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0021-9258(17)41116-1","article-title":"The mechanism of iodine concentration by the thyroid gland: Its non-organic iodine-binding capacity in the normal and propylthiouracil-treated rat","volume":"171","author":"Taurog","year":"1947","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0021-9258(18)55972-X","article-title":"Non-thyroglobulin iodine of the thyroid gland II. Inorganic iodide","volume":"191","author":"Taurog","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1089\/105072501750362745","article-title":"Estimation of total body iodine content in normal young men","volume":"11","author":"Hays","year":"2001","journal-title":"Thyroid"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00394-007-0694-3","article-title":"Influence of dietary iodine on the iodine content of pork and the distribution of the trace element in the body","volume":"47","author":"Franke","year":"2008","journal-title":"Eur. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00394-011-0247-7","article-title":"Effect of iodine source and dose on growth and iodine content in tissue and plasma thyroid hormones in fattening pigs","volume":"51","author":"Li","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1089\/105072501300176408","article-title":"The toxicology of iodate: A review of the literature","volume":"11","author":"Schaffner","year":"2001","journal-title":"Thyroid"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: Under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jpi.12267","article-title":"Melatonin: An ancient molecule that makes oxygen metabolically tolerable","volume":"59","author":"Manchester","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_32","first-page":"e13320","article-title":"Treatment with melatonin and selenium attenuates docetaxel-induced apoptosis and oxidative injury in kidney and testes of mice","volume":"51","year":"2019","journal-title":"Andrologia"},{"key":"ref_33","first-page":"1","article-title":"Melatonin attenuates diabetes-induces oxidative stress in spleen and suppression of splenocyte proliferation in laboratory mice","volume":"5","author":"Sutradhar","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.14715\/cmb\/2017.63.2.16","article-title":"The effects of melatonin on oxidative stress and prevention of primordial follicle loss via activation of mTOR pathway in the rat ovary","volume":"63","author":"Aydin","year":"2017","journal-title":"Cell Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0304-4165(00)00110-0","article-title":"Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by delta-aminolevulinic acid","volume":"1523","author":"Karbownik","year":"2000","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Morabito, R., Remigante, A., and Marino, A. (2019). Melatonin protects band 3 protein in human erythrocytes against H2O2-induced oxidative stress. Molecules, 24.","DOI":"10.3390\/molecules24152741"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jpi.12162","article-title":"Melatonin: A well documented antioxidant with conditional pro-oxidant actions","volume":"57","author":"Hang","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","unstructured":"Rothschild, M.F., and Ruvinsky, A. (2011). Pigs as a model for biomedical sciences. The Genetics of the Pig, CAB International. [2nd ed.].","DOI":"10.1079\/9781845937560.0000"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.beem.2009.08.010","article-title":"Iodine excess","volume":"24","year":"2010","journal-title":"Best Pract Res. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bbamem.2013.08.013","article-title":"The sodium\/iodide symporter: State of the art of its molecular characterization","volume":"1838","author":"Darrouzet","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1210\/en.2008-1437","article-title":"The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid","volume":"150","author":"Bizhanova","year":"2009","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-physiol-022516-034125","article-title":"The sodium\/iodide symporter (NIS): Molecular physiology and preclinical and clinical applications","volume":"79","author":"Ravera","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rynkowska, A., Stepniak, J., and Karbownik-Lewinska, M. (2020). Fenton reaction-induced oxidative damage to membrane lipids and protective effects of 17\u03b2-estradiol in porcine ovary and thyroid homogenates. Int. J. Environ. Res. Public Health., 17.","DOI":"10.3390\/ijerph17186841"},{"key":"ref_45","first-page":"343","article-title":"External hydrogen peroxide is not indispensable for experimental induction of lipid peroxidation via Fenton reaction in porcine ovary homogenates","volume":"31","author":"Stepniak","year":"2010","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.tiv.2012.09.010","article-title":"Membrane lipids and nuclear DNA are differently susceptive to Fenton reaction substrates in porcine thyroid","volume":"27","author":"Stepniak","year":"2013","journal-title":"Toxicol. In Vitro"},{"key":"ref_47","first-page":"309","article-title":"Toxicity and carcinogenicity of potassium bromate\u2014A new renal carcinogen","volume":"87","author":"Kurokawa","year":"1990","journal-title":"Environ. Health Perspect."},{"key":"ref_48","unstructured":"(2021, March 14). IARC Monographs\u2014Potassium Bromate. Available online: https:\/\/monographs.iarc.who.int\/wp-content\/uploads\/2018\/06\/mono73-22.pdf."},{"key":"ref_49","unstructured":"(2021, June 21). Osha Select Carcinogens. Available online: https:\/\/memphis.edu\/ehs\/pdfs\/carlist.pdf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/0024-3205(81)90600-7","article-title":"The pineal and melatonin in the regulation of pituitary thyroid axis","volume":"29","author":"Vriend","year":"1981","journal-title":"Life Sci."},{"key":"ref_51","first-page":"73","article-title":"REVIEW. Melatonin and the thyroid gland","volume":"23","author":"Karbownik","year":"2002","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/jpi.12010","article-title":"On the free radical scavenging activities of melatonin\u2019s metabolites, AFMK and AMK","volume":"54","author":"Galano","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_53","first-page":"325","article-title":"Melatonin: Exceeding expectations","volume":"29","author":"Reiter","year":"2014","journal-title":"Physiology (Bethesda)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2174\/1570159X14666161228122115","article-title":"Melatonin: Pharmacology, functions and therapeutic benefits","volume":"15","author":"Tordjman","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s40261-015-0368-5","article-title":"The safety of melatonin in humans","volume":"36","author":"Andersen","year":"2015","journal-title":"Clin. Drug Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/S0140-6736(84)90412-4","article-title":"Fall in nocturnal serum of melatonin during puberty and pubescence","volume":"1","author":"Waldhauser","year":"1984","journal-title":"Lancet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000510252","article-title":"Pharmacokinetics and safety of intravenous, intravesical, rectal, transdermal, and vaginal melatonin in healthy female volunteers: A cross-over study","volume":"106","author":"Zetner","year":"2021","journal-title":"Pharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s40266-014-0178-0","article-title":"Optimal dosages for melatonin supplementation therapy in older adults: A systematic review of current literature","volume":"31","author":"Vural","year":"2014","journal-title":"Drugs Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12639","DOI":"10.1111\/jpi.12639","article-title":"Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies","volume":"68","author":"Sato","year":"2020","journal-title":"J. Pineal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative stress and the Central Nervous System","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_61","first-page":"S40","article-title":"Oxidative stress and the ovary","volume":"8","author":"Behrman","year":"2001","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.3748\/wjg.v23.i16.2841","article-title":"Oxidative stress, antioxidants and intestinal calcium absorption","volume":"23","author":"Guizzardi","year":"2017","journal-title":"World J. Gastroenterol."}],"updated-by":[{"DOI":"10.3390\/life12071007","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000}}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/6\/592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:48:03Z","timestamp":1754261283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/6\/592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":62,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["life11060592"],"URL":"https:\/\/doi.org\/10.3390\/life11060592","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]}}}