{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T21:00:18Z","timestamp":1782939618713,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Potassium bromate (PB) is a well\u2010known additive in the food industry and a byproduct of water treatment. Its long\u2010term exposure to any form of life exerts mild to severe toxic insults in a dose\u2010dependent fashion and can even trigger carcinogenesis. This study examines the ameliorative effectiveness of a prominent polyphenol, naringenin (NIR), in rodents previously exposed to PB. The Swiss albino rats were assigned to five treatment groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095): Group I was the control, and Groups II and III were administered with PB alone (100\u2009mg\/kg) and NIR alone (2\u2009mg\/kg), respectively. The remaining two groups were treated with NIR at 2 and 4\u2009mg\/kg in the PB\u2010preadministered rats. The animals were sacrificed after the treatment course to retrieve their liver and blood for biochemical, molecular, and histological studies. The PB\u2010treated Group II showed a marked rise in liver function and toxicity markers in the serum samples, confirming hepatotoxicity after treatment. Disrupted redox markers (GSH and MDA) and compromised antioxidant enzymes (SOD and CAT) further support the hepatotoxicity induced by PB. Notably, NIR exhibited minimal toxicity, as indicated by Group III, and most of the measured parameters' values were comparable to those of the control. However, the combination groups (IV and V) showed improvement in the PB\u2010mediated hepatotoxicity assessment dose\u2010dependently. In addition, a prominent decline in LDH activity, concomitant with fan\u2010like comet formation in the nuclear DNA, is observed in these groups, suggesting that NIR promotes apoptosis concurrently with reducing necrosis. The histopathological investigation further consolidates these findings, showing marked structural restoration in liver histology, along with improved activity of antioxidant enzymes and a more favorable redox status. Hence, NIR can be utilized in consumer products with PB as an ingredient or to reduce hepatotoxicity induced by PB or similar compounds or potential drugs in\u00a0vivo.\n                  <\/jats:p>","DOI":"10.1002\/jat.4856","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T04:39:10Z","timestamp":1752899950000},"page":"2601-2612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Naringenin on Potassium Bromate\u2013Induced Hepatotoxicity In\u00a0Vivo: A Dose\u2010Dependent Study"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6993-9954","authenticated-orcid":false,"given":"Iftekhar","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-7820","authenticated-orcid":false,"given":"Hossam","family":"Ebaid","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-1152","authenticated-orcid":false,"given":"Badar\u00a0ul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Ram Gopal Medical College and Research Center  Hathras India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-2448","authenticated-orcid":false,"given":"Jameel","family":"Al\u2010Tamimi","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0058-1629","authenticated-orcid":false,"given":"Ibrahim\u00a0M.","family":"Alhazza","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altaaf","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Department of Pharmacology and Toxicology, Research Center, Central Lab King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-5575","authenticated-orcid":false,"given":"Ezzat\u00a0M.","family":"Awad","sequence":"additional","affiliation":[{"name":"Center of Ocular Inflammation and Infection, Laura Bassi Centres of Expertise (OCUVAC), Institute of Specific Prophylaxis and Tropical Medicine (ISPTM), Center for Pathophysiology, Infectiology and Immunology (CePII) Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17166"},{"key":"e_1_2_13_3_1","first-page":"121","volume-title":"Methods in enzymology","author":"Aebi H.","year":"1984"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-93120-3"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2022.503481"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants9121784"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114514000178"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165\u20101218(92)90231\u2010n"},{"issue":"17","key":"e_1_2_13_9_1","first-page":"3923","article-title":"Enhancement of Naringenin Bioavailability Through the Use of Nanocarriers: A Review","volume":"25","author":"Bae S. J.","year":"2020","journal-title":"Molecules"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.23386"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3791\/266"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.07.045"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00360"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17020200"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/109.9.1615"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076\u20106879(78)52032\u20106"},{"key":"e_1_2_13_17_1","first-page":"484","volume-title":"Glutathione Reductase. Methods in Enzymology","author":"Carlberg I.","year":"1985"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201062703\u2010290\u20102_7"},{"issue":"5","key":"e_1_2_13_19_1","first-page":"809","article-title":"Naringenin Inhibits Proliferation and Induces Apoptosis in Cancer Cells: A Review","volume":"144","author":"Choi H. S.","year":"2018","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339802600501"},{"key":"e_1_2_13_21_1","unstructured":"Environmental Protection Agency (EPA).2021.Potassium Bromate: Cancer Assessment Update.https:\/\/www.epa.gov."},{"key":"e_1_2_13_22_1","unstructured":"Food and Drug Administration (FDA).2021.Food Additives and Ingredients: Potassium Bromate.https:\/\/www.fda.gov."},{"key":"e_1_2_13_23_1","first-page":"162","article-title":"Naringenin Protects Against Oxidative Stress and Inflammation in Neuronal Cells: Implications for Neurodegenerative Diseases","volume":"135","author":"Gao Y.","year":"2019","journal-title":"Free Radical Biology and Medicine"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036273"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.07.018"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8274261"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9897315"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1528978"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000136485"},{"issue":"4","key":"e_1_2_13_30_1","first-page":"258","article-title":"Toxicological Study of Potassium Bromate I. Absorption Metabolism and Excretion of Potassium Bromate After Oral Administration in Rats","volume":"37","author":"Kawana K.","year":"1991","journal-title":"Japanese Journal of Toxicology and Environmental Health"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530320666200516163919"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/162750"},{"issue":"4","key":"e_1_2_13_33_1","first-page":"977","article-title":"Dose\u2010Response Studies on the Carcinogenicity of Potassium Bromate in F344 Rats After Long\u2010Term Oral Administration","volume":"77","author":"Kurokawa Y.","year":"1986","journal-title":"Journal of the National Cancer Institute"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9087309"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1974.tb03714.x"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18020248"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120752"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28103996"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400476"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2014.06.004"},{"issue":"3","key":"e_1_2_13_41_1","first-page":"123","article-title":"Chronic Effects of Potassium Bromate in Animal Models: Implications for Human Health","volume":"38","author":"Schoeny R.","year":"2020","journal-title":"Journal of Environmental Science and Health, Part C"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20104827(88)90265\u20100"},{"key":"e_1_2_13_43_1","first-page":"3","article-title":"Toxicological Properties of Potassium Bromate","volume":"1","author":"Starek A.","year":"2016","journal-title":"Journal of Pharmacological Reports."},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2012.12.010"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu5093367"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.3.593"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2017.12.004"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4856","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:41:43Z","timestamp":1776062503000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jat.4856"],"URL":"https:\/\/doi.org\/10.1002\/jat.4856","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"assertion":[{"value":"2025-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}