{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T12:59:12Z","timestamp":1786798752587,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n FUESCYL-Banco Santander","award":["Ed. 2014\u20132015 Desaf\u00edo UNIV-EMP"],"award-info":[{"award-number":["Ed. 2014\u20132015 Desaf\u00edo UNIV-EMP"]}]},{"name":"Fundaci\u00f3n General de la Universidad de Salamanca, Fondo Europeo de Desarrollo Regional (FEDER) y la Junta de Castilla y Le\u00f3n","award":["Ed. 2015 Lanzadera TC"],"award-info":[{"award-number":["Ed. 2015 Lanzadera TC"]}]},{"DOI":"10.13039\/501100008431","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["VA225U14"],"award-info":[{"award-number":["VA225U14"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministerio de Ciencia, Innovaci\u00f3n","award":["Project PID2019-106167RB-I00"],"award-info":[{"award-number":["Project PID2019-106167RB-I00"]}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["Project SA093P20"],"award-info":[{"award-number":["Project SA093P20"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Research Programs for Units of Excellence from Junta de Castilla y Le\u00f3n","award":["CLU-2018-04"],"award-info":[{"award-number":["CLU-2018-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Quercetin, a flavonoid with promising therapeutic potential, has been shown to protect from cisplatin nephrotoxicity in rats following intraperitoneal injection, but its low bioavailability curtails its prospective clinical utility in oral therapy. We recently developed a micellar formulation (P-quercetin) with enhanced solubility and bioavailability, and identical nephroprotective properties. As a first aim, we herein evaluated the oral treatment with P-quercetin in rats, which displayed no nephroprotection. In order to unravel this discrepancy, quercetin and its main metabolites were measured by HPLC in the blood and urine after intraperitoneal and oral administrations. Whilst quercetin was absorbed similarly, the profile of its metabolites was different, which led us to hypothesize that nephroprotection might be exerted in vivo by a metabolic derivate. Consequently, we then aimed to evaluate the cytoprotective capacity of quercetin and its main metabolites (quercetin 3-O-glucoside, rutin, tamarixetin, isorhamnetin and quercetin 3-O-glucuronide) against cisplatin toxicity, in HK-2 and NRK-52E tubular cell lines. Cells were incubated for 6 h with quercetin, its metabolites or vehicle (pretreatment), and subsequently 18 h in cotreatment with 10\u2013300 \u03bcM cisplatin. Immediately after treatment, cell cultures were subject to the MTT technique as an index of cytotoxicity and photographed under light microscopy for phenotypic assessment. Quercetin afforded no direct cytoprotection and quercetin-3-O-glucuronide was the only metabolite partially preventing the effect of cisplatin in cultured tubule cells. Our results identify a metabolic derivative of quercetin contributing to its nephroprotection and prompt to further explore exogenous quercetin-3-O-glucuronide in the prophylaxis of tubular nephrotoxicity.<\/jats:p>","DOI":"10.3390\/molecules27041319","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T22:44:47Z","timestamp":1644965087000},"page":"1319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Protective Effect of Quercetin 3-O-Glucuronide against Cisplatin Cytotoxicity in Renal Tubular Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8464-1996","authenticated-orcid":false,"given":"Daniel","family":"Mu\u00f1oz-Reyes","sequence":"first","affiliation":[{"name":"Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0725-6637","authenticated-orcid":false,"given":"Alfredo G.","family":"Casanova","sequence":"additional","affiliation":[{"name":"Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-0703","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Gonz\u00e1lez-Param\u00e1s","sequence":"additional","affiliation":[{"name":"Polyphenols Research Group (GIP-USAL), Nutrition and Bromatology Unit, Faculty of Pharmacy, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"High Pressure Processes Group, BioEcoUVa, Bioeconomy Research Institute, Department of Chemical Engineering and Environmental Technology, Universidad de Valladolid, 47011 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-5299","authenticated-orcid":false,"given":"Celestino","family":"Santos-Buelga","sequence":"additional","affiliation":[{"name":"Polyphenols Research Group (GIP-USAL), Nutrition and Bromatology Unit, Faculty of Pharmacy, Universidad de Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-6138","authenticated-orcid":false,"given":"Ana I.","family":"Morales","sequence":"additional","affiliation":[{"name":"Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7778-7495","authenticated-orcid":false,"given":"Francisco J.","family":"L\u00f3pez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-4461","authenticated-orcid":false,"given":"Marta","family":"Prieto","sequence":"additional","affiliation":[{"name":"Toxicology Unit, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Department of Physiology and Pharmacology, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"National Network for Kidney Research REDINREN, RD016\/0009\/0025, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/MAJ.0b013e31812dfe1e","article-title":"Cisplatin Nephrotoxicity: A Review","volume":"334","author":"Yao","year":"2007","journal-title":"Am. 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