{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:57Z","timestamp":1787028537847,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","award":["21-1274"],"award-info":[{"award-number":["21-1274"]}]},{"name":"Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","award":["A1-S-9870"],"award-info":[{"award-number":["A1-S-9870"]}]},{"name":"Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","award":["IN209522"],"award-info":[{"award-number":["IN209522"]}]},{"DOI":"10.13039\/501100003141","name":"the sectoral research fund for education","doi-asserted-by":"publisher","award":["21-1274"],"award-info":[{"award-number":["21-1274"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"the sectoral research fund for education","doi-asserted-by":"publisher","award":["A1-S-9870"],"award-info":[{"award-number":["A1-S-9870"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"the sectoral research fund for education","doi-asserted-by":"publisher","award":["IN209522"],"award-info":[{"award-number":["IN209522"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)","award":["21-1274"],"award-info":[{"award-number":["21-1274"]}]},{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)","award":["A1-S-9870"],"award-info":[{"award-number":["A1-S-9870"]}]},{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM)","award":["IN209522"],"award-info":[{"award-number":["IN209522"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin\u2013eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.<\/jats:p>","DOI":"10.3390\/ijms25115881","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T07:38:39Z","timestamp":1716881919000},"page":"5881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-668X","authenticated-orcid":false,"given":"Roc\u00edo","family":"Bautista-P\u00e9rez","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustina","family":"Cano-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Alejandro","family":"Herrera-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Pilar","family":"Ramos-Godinez","sequence":"additional","affiliation":[{"name":"Departamento de Microscop\u00eda Electr\u00f3nica, Instituto Nacional de Cancerolog\u00eda, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Lidia","family":"P\u00e9rez Reyes","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda Irasema","family":"Chirino","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 54090, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zari\u00e1 Jos\u00e9","family":"Rodr\u00edguez Serrano","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"L\u00f3pez-Marure","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1007\/s00253-020-10372-x","article-title":"The emerging role of metallic nanoparticles in food","volume":"104","author":"Ingle","year":"2020","journal-title":"Appl. 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