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We aimed to characterize the in vitro and in vivo interaction of ABCG2 with lumichrome, the main photodegradation product of riboflavin, which has proven in vitro anti-cancer activity and a therapeutical role in antibacterial photodynamic therapy as an efficient photosensitizer. Using MDCK-II polarized cells overexpressing murine Abcg2 and human ABCG2 we found that lumichrome was efficiently transported by both variants. After lumichrome administration to wild-type and Abcg2-\/- mice, plasma AUC20\u2013120 min was 1.8-fold higher in Abcg2-\/- mice compared with wild-type mice. The liver and testis from Abcg2-\/- mice showed significantly higher lumichrome levels compared with wild-type, whereas lumichrome accumulation in small intestine content of wild-type mice was 2.7-fold higher than in Abcg2-\/- counterparts. Finally, a 4.1-fold-higher lumichrome accumulation in milk of wild-type versus Abcg2-\/- mice was found. Globally, our results show that ABCG2 plays a crucial role in plasma levels, tissue distribution and milk secretion of lumichrome potentially conditioning its biological activity.<\/jats:p>","DOI":"10.3390\/ijms25189884","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T03:03:37Z","timestamp":1726196617000},"page":"9884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The ABCG2 Transporter Affects Plasma Levels, Tissue Distribution and Milk Secretion of Lumichrome, a Natural Derivative of Riboflavin"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6619-6428","authenticated-orcid":false,"given":"Alicia","family":"Mill\u00e1n-Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences\u2013Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-4034","authenticated-orcid":false,"given":"Laura","family":"\u00c1lvarez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences\u2013Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-1094","authenticated-orcid":false,"given":"Esther","family":"Blanco-Paniagua","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences\u2013Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana I.","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences\u2013Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-3475","authenticated-orcid":false,"given":"Gracia","family":"Merino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences\u2013Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.addr.2008.08.007","article-title":"Physiological and pharmacological roles of ABCG2 (BCRP): Recent findings in Abcg2 knockout mice","volume":"61","author":"Vlaming","year":"2008","journal-title":"Adv. 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