{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:21:14Z","timestamp":1767871274581,"version":"3.49.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    This study aimed to explore and reassess the safety and efficacy of the synthetic food dye erythrosine (ERY) with respect to the hepatic biomarkers and histological changes in male adult rats as well as possibly alleviate the effects of ERY through administration of lycopene (LYC) and anthocyanin (ANC). Sixty adult male rats were randomly distributed into six experimental groups as follows: control, LYC (5\u00a0mg\/kg), ANC (200\u00a0mg\/kg), ERY (20\u00a0mg\/kg), ERY + LYC, and ERY + ANC. After 3 and 6 weeks of treatment, ERY (20\u00a0mg\/kg) produced marked biochemical and hepatic injuries. ERY significantly reduced the total protein (from 6.93\u00a0g\/dL in control to 5.33\u00a0g\/dL) and albumin (from 2.65 to 1.77\u00a0g\/dL,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.050), whereas LYC and ANC co-administration improved these values compared to ERY alone (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.050). ERY was also found to elevate the total cholesterol, triglycerides (TG), and low-density lipoprotein (LDL) values relative to the control, whereas both LYC and ANC lowered LDL and TG levels compared to the ERY-treated rats. The liver injury markers were strongly increased by ERY, with alanine transaminase (ALT) increasing from 14.00 to 23.95 U\/L, aspartate transaminase (AST) increasing from 41.54 to 52.90 U\/L, and gamma-glutamyl transferase (GGT) increasing from 6.24 to 8.64 U\/L. Cotreatment with LYC or ANC was seen to significantly reduce ALT, AST, and GGT (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.050). The total bilirubin increased significantly in the ERY group but was restored to near-control levels with both LYC and ANC. Histologically, ERY produced moderate-to-severe focal hepatic degeneration, including hepatocyte cytoplasmic vacuolation (score 2\u20133), nuclear chromatin clumping (score 2), focal necrosis (score 2), and leukocytic infiltration (score 2\u20133); LYC and ANC markedly ameliorated these lesions, reducing the pathological scores to 0\u20131, while restoring the hepatic cords, sinusoids, and nuclear morphology to near-normal or normal appearance by week 6. Collectively, ERY impacted the hepatic chemistry and functionality with considerable effect on the histological appearance of the hepatic tissues in rats, while ANC and LYC resourcefully attenuated these adverse effects.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2025.1718792","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:36:25Z","timestamp":1767854185000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Erythrosine-induced hepatic biomarkers and histopathological changes in male rats: protective effects of lycopene and anthocyanin"],"prefix":"10.3389","volume":"16","author":[{"given":"Safa H.","family":"Qahl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatimah A.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haleema","family":"Al-Nahari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fawzyah A.","family":"Alghamdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatimah H.","family":"Khouja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna H.","family":"Khouja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5938","DOI":"10.1038\/s41598-023-32887-9","article-title":"Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats","volume":"13","author":"Abd-Elhakim","year":"2023","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5167524","DOI":"10.1155\/2018\/5167524","article-title":"Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-Induced toxicity in female wistar rats","volume":"2018","author":"Abdel-Rahman","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.2903\/j.efsa.2011.1854","article-title":"Scientific opinion on the re-evaluation of erythrosine (E 127) as a food additive","volume":"9","author":"Additives","year":"2011","journal-title":"EFSA J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.9734\/JAMMR\/2020\/v32i1730636","article-title":"Comparing the effect of methods of rat euthanasia on the brain of wistar rats: cervical dislocation, chloroform inhalation, diethyl ether inhalation and formalin inhalation","volume":"32","author":"Aguwa","year":"2020","journal-title":"J. Adv. Med. Med. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"111831","DOI":"10.1016\/j.biopha.2021.111831","article-title":"Lycopene corrects metabolic syndrome and liver injury induced by high fat diet in Obese rats through antioxidant, anti-inflammatory, antifibrotic pathways","volume":"141","author":"Albrahim","year":"2021","journal-title":"Biomed. and Pharmacother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"72","DOI":"10.5539\/gjhs.v8n3p72","article-title":"Histological stains: a literature review and case study","volume":"8","author":"Alturkistani","year":"2015","journal-title":"Glob. Journal Health Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1016\/j.foodchem.2013.05.026","article-title":"Interaction of anthocyanins with human serum albumin: influence of pH and chemical structure on binding","volume":"141","author":"Cahyana","year":"2013","journal-title":"Food Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"8960","DOI":"10.1039\/d1fo01039e","article-title":"Lycopene modulates lipid metabolism in rats and their offspring under a high-fat diet","volume":"12","author":"Cao","year":"2021","journal-title":"Food Funct."},{"key":"B9","doi-asserted-by":"publisher","first-page":"12896","DOI":"10.1038\/s41598-021-92377-8","article-title":"Physico-chemical characterization of bilirubin-10-sulfonate and comparison of its acid\u2013base behavior with unconjugated bilirubin","volume":"11","author":"\u010cepa","year":"2021","journal-title":"Sci. Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"147","DOI":"10.31083\/j.rcm2304147","article-title":"Review of laboratory methods to determine HDL and LDL subclasses and their clinical importance","volume":"23","author":"Chary","year":"2022","journal-title":"Rev. Cardiovasc. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1016\/j.fct.2012.07.042","article-title":"Genotoxic and mutagenic effects of erythrosine B, a xanthene food dye, on HepG2 cells","volume":"50","author":"Chequer","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"102273","DOI":"10.1016\/j.redox.2022.102273","article-title":"A randomized placebo-controlled cross-over study on the effects of anthocyanins on inflammatory and metabolic responses to a high-fat meal in healthy subjects","volume":"51","author":"Cremonini","year":"2022","journal-title":"Redox Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"397","DOI":"10.21449\/ijate.1101295","article-title":"Comparison of normality tests in terms of sample sizes under different skewness and Kurtosis coefficients","volume":"9","author":"Demir","year":"2022","journal-title":"Int. J. Assess. Tools Educ."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e3000411","DOI":"10.1371\/journal.pbio.3000411","article-title":"Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0","volume":"18","author":"Du Sert","year":"2020","journal-title":"PLoS Biology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"102975","DOI":"10.1016\/j.tice.2025.102975","article-title":"Lycopene alleviates cognitive dysfunctions in an Alzheimer's disease rat model via suppressing the oxidative and neuroinflammatory signaling","volume":"96","author":"El-Kazaz","year":"2025","journal-title":"Tissue Cell"},{"key":"B16","volume-title":"SAS essentials: mastering SAS for data analytics","author":"Elliott","year":"2023"},{"key":"B17","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1186\/s13104-019-4841-8","article-title":"Lycopene improves on basic hematological and immunological parameters in diabetes mellitus","volume":"12","author":"Eze","year":"2019","journal-title":"BMC Res. Notes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1601083","DOI":"10.1002\/mnfr.201601083","article-title":"Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders","volume":"61","author":"Fenni","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1016\/j.cgh.2020.08.006","article-title":"Measurement of gamma glutamyl transferase to determine risk of liver transplantation or death in patients with primary biliary cholangitis","volume":"19","author":"Gerussi","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"876","DOI":"10.12944\/CRNFSJ.7.3.26","article-title":"Toxic effects of food colorants erythrosine and tartrazine on zebrafish embryo development","volume":"7","author":"Gupta","year":"2019","journal-title":"Curr. Res. Nutr. Food Sci. J."},{"key":"B21","first-page":"184","article-title":"Mutagenic effects of the food colour erythrosine in rats","volume":"43","author":"Hamdy","year":"2000","journal-title":"Probl. Forensic Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"121131","DOI":"10.1016\/j.lfs.2022.121131","article-title":"Promising hepatoprotective effects of lycopene in different liver diseases","volume":"310","author":"Ibrahim","year":"2022","journal-title":"Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1080\/15376516.2020.1828523","article-title":"Combine colorants of tartrazine and erythrosine induce kidney injury: involvement of TNF-alpha gene, caspase-9 and KIM-1 gene expression and kidney functions indices","volume":"31","author":"Iheanyichukwu","year":"2021","journal-title":"Toxicol. Mech. Methods"},{"key":"B24","doi-asserted-by":"publisher","first-page":"10180","DOI":"10.3748\/wjg.v22.i46.10180","article-title":"Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat","volume":"22","author":"Jiang","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"B25","first-page":"701","volume-title":"Food additives","author":"Lindsay","year":"2007"},{"key":"B26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.21608\/jes.2019.67965","article-title":"Effect of synthetic coloring dye erythrosine (E127) in rats","volume":"46","author":"Marwa","year":"2019","journal-title":"J. Environ. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41586-023-06497-4","article-title":"Identification of an alternative triglyceride biosynthesis pathway","volume":"621","author":"McLelland","year":"2023","journal-title":"Nature"},{"key":"B28","first-page":"184","article-title":"Mutagenic effects of the food color erythrosine in rats. Probl","volume":"43","author":"Mekkawy","year":"2000","journal-title":"Forensic Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"737","DOI":"10.3390\/nu2070737","article-title":"Dietary polyphenols and obesity","volume":"2","author":"Meydani","year":"2010","journal-title":"Nutrients"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.3390\/ijms23042149","article-title":"Anthocyanins: traditional uses, structural and functional variations, approaches to increase yields and products' quality, hepatoprotection, liver longevity, and commercial products","volume":"23","author":"Mohammed","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1016\/j.fct.2010.07.030","article-title":"Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine","volume":"48","author":"Mpountoukas","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"102403","DOI":"10.1016\/j.fbio.2023.102403","article-title":"Natural pigments: anthocyanins, carotenoids, chlorophylls, and betalains as colorants in food products","volume":"52","author":"Nabi","year":"2023","journal-title":"Food Biosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e822","DOI":"10.1016\/j.wneu.2019.11.017","article-title":"Effects of erythrosine on neural tube development in early chicken embryos","volume":"134","author":"Ovalioglu","year":"2020","journal-title":"World Neurosurg."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1201\/9780429340512","volume-title":"Principles of biostatistics","author":"Pagano","year":"2022"},{"key":"B35","doi-asserted-by":"publisher","first-page":"106523","DOI":"10.1016\/j.jff.2024.106523","article-title":"Blueberry anthocyanins regulate SIRT1\/FoxO1 pathway to inhibit oxidative stress and reduce testicular tissue damage induced by microwave radiation in rats","volume":"122","author":"Pang","year":"2024","journal-title":"J. Funct. Foods"},{"key":"B36","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/s0006-291x(02)00927-0","article-title":"The interaction of anthocyanins with bilitranslocase","volume":"296","author":"Passamonti","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"114044","DOI":"10.1016\/j.biopha.2022.114044","article-title":"Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats","volume":"157","author":"Pelizzo","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4457","DOI":"10.1007\/s00216-022-03910-1","article-title":"Determination of the protein content of complex samples by aromatic amino acid analysis, liquid chromatography-UV absorbance, and colorimetry","volume":"414","author":"Reinmuth-Selzle","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s00210-022-02234-2","article-title":"Phytochemicals targeting NAFLD through modulating the dual function of forkhead box O1 (FOXO1) transcription factor signaling pathways","volume":"395","author":"Sabir","year":"2022","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6829409","DOI":"10.1155\/2024\/9792751","article-title":"Toxicological and teratogenic effect of various food additives: an updated review","volume":"2022","author":"Sambu","year":"2022","journal-title":"BioMed. Res. Int."},{"key":"B41","doi-asserted-by":"publisher","first-page":"43","DOI":"10.31024\/ajpp.2019.5.1.5","article-title":"Biochemical and pharmacological estimation of erythrosine in myocardial remodeling among heart failure induced by doxorubicin in rats","volume":"5","author":"Saqib","year":"2019","journal-title":"Asian J. Pharm. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"366","DOI":"10.9755\/ejfa.2016-04-351","article-title":"Food preservatives\u2013An overview on applications and side effects","volume":"28","author":"Silva","year":"2016","journal-title":"Emir. J. Food Agric."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s11094-023-02811-6","article-title":"Hepatoprotective efficacy of a new phytocomposition of essential phospholipids with glycyrrhizic acid, ecdysterone, and lycopene in experimental chronic hepatitis compared to phosphogliv","volume":"56","author":"Syrov","year":"2023","journal-title":"Pharm. Chem. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"20240973","DOI":"10.1515\/med-2024-0973","article-title":"Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK\/mTOR\/NLRP3 pathway","volume":"19","author":"Tan","year":"2024","journal-title":"Open Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"102670","DOI":"10.1016\/j.fbio.2023.102670","article-title":"Recent advances on the biological activities of purple sweet potato anthocyanins","volume":"53","author":"Tang","year":"2023","journal-title":"Food Biosci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e08454","DOI":"10.1016\/j.heliyon.2021.e08454","article-title":"Involvement of striatal oxido-inflammatory, nitrosative and decreased cholinergic activity in neurobehavioral alteration in adult rat model with oral co-exposure to erythrosine and tartrazine","volume":"7","author":"Wopara","year":"","journal-title":"Heliyon"},{"key":"B47","doi-asserted-by":"publisher","first-page":"341","DOI":"10.5935\/1518-0557.20200097","article-title":"Synthetic Food dyes cause testicular damage via up-regulation of pro-inflammatory cytokines and down-regulation of FSH-R and TESK-1 gene expression","volume":"25","author":"Wopara","year":"","journal-title":"JBRA Assist. Reprod."},{"key":"B48","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3390\/chemosensors9050098","article-title":"Recent development in nanomaterial-based electrochemical sensors for cholesterol detection","volume":"9","author":"Yadav","year":"2021","journal-title":"Chemosensors"},{"key":"B49","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.procbio.2022.01.010","article-title":"Current Advancement in biosensing techniques for determination of Alanine aminotransferase and Aspartate aminotransferase-a Mini Review","volume":"114","author":"Yadav","year":"2022","journal-title":"Process Biochem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1002\/tox.23807","article-title":"High-dose synthetic phenolic antioxidant propyl gallate impairs mouse oocyte meiotic maturation through inducing mitochondrial dysfunction and DNA damage","volume":"38","author":"Yang","year":"2023","journal-title":"Environ. Toxicol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"95","DOI":"10.54203\/scil.2023.wvj10","article-title":"Effects of the anthocyanin compound (Cyanidin-3-Glucoside) on some histological and physiological parameters related to the heart in Male rats exposed to oxidative stress","volume":"13","author":"Yasser","year":"2023","journal-title":"World's Veterinary J."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JBR-170167","article-title":"Structure-affinity relationship of dietary anthocyanin\u2013HSA interaction","volume":"8","author":"Zhang","year":"2018","journal-title":"J. Berry Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1718792\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:36:27Z","timestamp":1767854187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1718792\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":52,"alternative-id":["10.3389\/fphar.2025.1718792"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1718792","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"article-number":"1718792"}}