{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:05:44Z","timestamp":1784639144906,"version":"3.55.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100015773","name":"Instituto Nacional de Cardiolog\u00eda - Ignacio Ch\u00e1vez","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015773","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["IMSS2006\/1\\u2009A\/075"],"award-info":[{"award-number":["IMSS2006\/1\\u2009A\/075"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["IMSS2012FIS\/IMSS\/PROT\/G12\/1106"],"award-info":[{"award-number":["IMSS2012FIS\/IMSS\/PROT\/G12\/1106"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology and Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.etap.2026.105090","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:00:38Z","timestamp":1783062038000},"page":"105090","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Titanium dioxide food additive (E171) and zinc oxide nanoparticles alter coagulation markers in endothelial cells and activate platelets"],"prefix":"10.1016","volume":"125","author":[{"given":"Norma Ang\u00e9lica","family":"Corona de la Pe\u00f1a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Angel P\u00e9rez","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belen Romo","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"del Valle Mondrag\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"del Pilar Ramos-God\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cabello-Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"L\u00f3pez-Marure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.etap.2026.105090_bib1","article-title":"Nitric oxide: physiological functions, delivery, and biomedical applications","volume":"10","author":"Andrabi","year":"2023","journal-title":"Adv. Sci. (Weinh. )"},{"key":"10.1016\/j.etap.2026.105090_bib2","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1161\/01.CIR.91.3.619","article-title":"Differential expression of tissue factor protein in directional atherectomy specimens from patients with stable and unstable coronary syndromes","volume":"91","author":"Annex","year":"1995","journal-title":"Circulation"},{"key":"10.1016\/j.etap.2026.105090_bib3","doi-asserted-by":"crossref","DOI":"10.1088\/2053-1591\/1\/3\/035041","article-title":"Biological interactions in vitro of zinc oxide nanoparticles of different characteristics","volume":"1","author":"Aula","year":"2014","journal-title":"Mater. Res. Express"},{"key":"10.1016\/j.etap.2026.105090_bib4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tox.2009.08.011","article-title":"Single-walled carbon nanotubes activate platelets and accelerate thrombus formation in the microcirculation","volume":"269","author":"Bihari","year":"2010","journal-title":"Toxicology"},{"key":"10.1016\/j.etap.2026.105090_bib5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.fct.2016.05.008","article-title":"Effects of zinc oxide nanoparticles on human coronary artery endothelial cells","volume":"93","author":"Chuang","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s12012-022-09747-5","article-title":"Titanium dioxide (E171) induces toxicity in H9c2 rat cardiomyoblasts and Ex vivo rat hearts","volume":"22","author":"Colin-Val","year":"2022","journal-title":"Cardiovasc. Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0182374","article-title":"Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets","volume":"12","author":"Corona de la Pe\u00f1a","year":"2017","journal-title":"PLoS. One"},{"key":"10.1016\/j.etap.2026.105090_bib8","first-page":"751","article-title":"Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress","volume":"11","author":"Dorier","year":"2017","journal-title":"Nanotoxicology"},{"key":"10.1016\/j.etap.2026.105090_bib9","doi-asserted-by":"crossref","first-page":"a008904","DOI":"10.1101\/cshperspect.a008904","article-title":"Signaling pathways that control cell proliferation","volume":"5","author":"Duronio","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.etap.2026.105090_bib10","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.3390\/ijerph20032002","article-title":"DNA damage and apoptosis as in-vitro effect biomarkers of titanium dioxide nanoparticles (TiO2-NPs) and the food additive E171 toxicity in colon cancer cells: HCT-116 and Caco-2","volume":"20","author":"Ferrante","year":"2023","journal-title":"Int. J. Environ. Res. Public. Health"},{"key":"10.1016\/j.etap.2026.105090_bib11","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00204-016-1765-0","article-title":"Oral uptake of nanoparticles: human relevance and the role of in vitro systems","volume":"90","author":"Fr\u00f6hlich","year":"2016","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib12","doi-asserted-by":"crossref","DOI":"10.1111\/j.1542-4758.2006.00119.x","article-title":"Coagulation cascade","volume":"10","author":"Green","year":"2006","journal-title":"Hemodial. Int."},{"key":"10.1016\/j.etap.2026.105090_bib13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3109\/17435390.2014.992815","article-title":"Effects of acute systemic administration of TiO2, ZnO, SiO2, and Ag nanoparticles on hemodynamics, hemostasis and leukocyte recruitment","volume":"9","author":"Haberl","year":"2015","journal-title":"Nanotoxicology"},{"key":"10.1016\/j.etap.2026.105090_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tox.2013.01.014","article-title":"Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells","volume":"306","author":"Han","year":"2013","journal-title":"Toxicology"},{"key":"10.1016\/j.etap.2026.105090_bib15","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMra043430","article-title":"Inflammation, atherosclerosis, and coronary artery disease","volume":"352","author":"Hansson","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.etap.2026.105090_bib16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12989-023-00553-7","article-title":"Food-grade titanium dioxide and zinc oxide nanoparticles induce toxicity and cardiac damage after oral exposure in rats","volume":"20","author":"Herrera-Rodr\u00edguez","year":"2023","journal-title":"Part. Fibre Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib17","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1039\/C5FO00630A","article-title":"Zinc as a micronutrient and its preventive role of oxidative damage in cells","volume":"6","author":"Kloubert","year":"2015","journal-title":"Food Funct."},{"key":"10.1016\/j.etap.2026.105090_bib18","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/9156285","article-title":"Critical role of zinc as either an antioxidant or a prooxidant in cellular systems","volume":"2018","author":"Lee","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.etap.2026.105090_bib19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41392-024-02095-6","article-title":"Redox regulation: mechanisms, biology and therapeutic targets in diseases","volume":"10","author":"Li","year":"2025","journal-title":"Signal. Transduct. Target. Ther."},{"key":"10.1016\/j.etap.2026.105090_bib20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cbi.2016.08.013","article-title":"Role of Cyt-C\/caspases-9,3, Bax\/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid","volume":"258","author":"Liang","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.etap.2026.105090_bib21","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/tox.22821","article-title":"The size-dependent genotoxic potentials of titanium dioxide nanoparticles to endothelial cells","volume":"34","author":"Liao","year":"2019","journal-title":"Environ. Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib22","doi-asserted-by":"crossref","DOI":"10.1002\/ppsc.201800547","article-title":"Interference of metal oxide nanoparticles with coagulation cascade and interaction with blood components","volume":"36","author":"Lozano-Fern\u00e1ndez","year":"2019","journal-title":"Part. & Part. Syst. Charact."},{"key":"10.1016\/j.etap.2026.105090_bib23","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.envpol.2012.08.011","article-title":"Ecotoxicity of manufactured ZnO nanoparticles--a review","volume":"172","author":"Ma","year":"2013","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.etap.2026.105090_bib24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cis.2017.05.010","article-title":"Physicochemical and colloidal aspects of food matrix effects on gastrointestinal fate of ingested inorganic nanoparticles","volume":"246","author":"McClements","year":"2017","journal-title":"Adv. Colloid Interface Sci."},{"key":"10.1016\/j.etap.2026.105090_bib25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI114175","article-title":"GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies","volume":"84","author":"McEver","year":"1989","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.etap.2026.105090_bib26","doi-asserted-by":"crossref","first-page":"12940","DOI":"10.3390\/ijms232112940","article-title":"Zinc Oxide Nanoparticles Induce Toxicity in H9c2 Rat Cardiomyoblasts","volume":"23","author":"Mendoza-Milla","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.etap.2026.105090_bib27","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1021\/tx200551u","article-title":"TiO\u2082 nanoparticles induce dysfunction and activation of human endothelial cells","volume":"25","author":"Montiel-D\u00e1valos","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.etap.2026.105090_bib28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00441-021-03471-2","article-title":"Endothelial cells and coagulation","volume":"387","author":"Neubauer","year":"2022","journal-title":"Cell. Tissue Res."},{"key":"10.1016\/j.etap.2026.105090_bib29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.etap.2014.11.021","article-title":"Identification of titanium dioxide nanoparticles in food products: induce intracellular oxidative stress mediated by TNF and CYP1A genes in human lung fibroblast cells","volume":"39","author":"Periasamy","year":"2015","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"10.1016\/j.etap.2026.105090_bib30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnut.2014.00014","article-title":"Zinc is an antioxidant and anti-inflammatory agent: its role in human health","volume":"1","author":"Prasad","year":"2014","journal-title":"Front. Nutr."},{"key":"10.1016\/j.etap.2026.105090_bib31","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/sj.bjp.0706386","article-title":"Nanoparticle-induced platelet aggregation and vascular thrombosis","volume":"146","author":"Radomski","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.etap.2026.105090_bib32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1179\/1607845412Y.0000000035","article-title":"Protein anticoagulants targeting factor VIIa\u2013tissue factor complex: a comprehensive review","volume":"18","author":"Shah","year":"2013","journal-title":"Hematology"},{"key":"10.1016\/j.etap.2026.105090_bib33","doi-asserted-by":"crossref","first-page":"236","DOI":"10.12688\/f1000research.13283.1","article-title":"The life cycle of platelet granules","volume":"7","author":"Sharda","year":"2018","journal-title":"F1000Res"},{"key":"10.1016\/j.etap.2026.105090_bib34","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41580-024-00730-2","article-title":"Fundamentals of redox regulation in biology","volume":"25","author":"Sies","year":"2024","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"10.1016\/j.etap.2026.105090_bib35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1746-6148-9-7","article-title":"Effect of engineered TiO2 and ZnO nanoparticles on erythrocytes, platelet-rich plasma and giant unilamelar phospholipid vesicles","volume":"9","author":"\u0160imundi\u0107","year":"2013","journal-title":"BMC Vet. Res."},{"key":"10.1016\/j.etap.2026.105090_bib36","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1080\/15376516.2018.1553221","article-title":"Zinc oxide nanoparticles impacts: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity","volume":"29","author":"Singh","year":"2019","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.etap.2026.105090_bib37","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/jbm.b.33051","article-title":"Metallic oxide nanoparticles stimulate blood coagulation independent of their surface charge","volume":"102","author":"Steuer","year":"2014","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."},{"key":"10.1016\/j.etap.2026.105090_bib38","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.taap.2014.04.010","article-title":"Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation","volume":"278","author":"Suzuki","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.etap.2026.105090_bib39","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1160\/TH14-12-1067","article-title":"The role of platelets in inflammation","volume":"114","author":"Thomas","year":"2015","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.etap.2026.105090_bib40","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tcm.2015.12.001","article-title":"Tissue factor as a link between inflammation and coagulation","volume":"26","author":"Witkowski","year":"2016","journal-title":"Trends Cardiovasc. Med."},{"key":"10.1016\/j.etap.2026.105090_bib41","article-title":"Surface functionalization-specific binding of coagulation factors by zinc oxide nanoparticles delays coagulation time and reduces thrombin generation potential in vitro","volume":"12","author":"Yang","year":"2017","journal-title":"PLoS. One"},{"key":"10.1016\/j.etap.2026.105090_bib42","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/9060143","article-title":"Platelet Activation: the mechanisms and potential biomarkers","volume":"2016","author":"Yun","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.etap.2026.105090_bib43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.msec.2017.08.024","article-title":"Effect of crystalline phase changes in titania (TiO2) nanotube coatings on platelet adhesion and activation","volume":"82","author":"Zhang","year":"2018","journal-title":"Mater. Sci. Eng. C. Mater. Biol. Appl."},{"key":"10.1016\/j.etap.2026.105090_bib44","doi-asserted-by":"crossref","first-page":"37789","DOI":"10.1039\/C8RA07315E","article-title":"Platelet aggregation induced by polystyrene and platinum nanoparticles is dependent on surface area","volume":"8","author":"Zia","year":"2018","journal-title":"RSC Adv."}],"container-title":["Environmental Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1382668926001687?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1382668926001687?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:53:52Z","timestamp":1784638432000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1382668926001687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":44,"alternative-id":["S1382668926001687"],"URL":"https:\/\/doi.org\/10.1016\/j.etap.2026.105090","relation":{},"ISSN":["1382-6689"],"issn-type":[{"value":"1382-6689","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Titanium dioxide food additive (E171) and zinc oxide nanoparticles alter coagulation markers in endothelial cells and activate platelets","name":"articletitle","label":"Article Title"},{"value":"Environmental Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.etap.2026.105090","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105090"}}