{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:43:10Z","timestamp":1793317390224,"version":"4.5.0"},"reference-count":64,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"Texas A&M College of Pharmacy","award":["Startup Grant"],"award-info":[{"award-number":["Startup Grant"]}]},{"name":"UA Merit Award","award":["BX002006"],"award-info":[{"award-number":["BX002006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:p>\n                    The popular anticancer drug cisplatin causes many adverse side effects, the most serious of which is acute kidney injury (AKI). Emerging evidence from laboratory and clinical studies suggests that the AKI pathogenesis involves oxidative stress pathways; therefore, regulating such pathways may offer protection. Urolithin A (UA), a gut metabolite of the dietary tannin ellagic acid, possesses antioxidant properties and has shown promise in mouse models of AKI. However, therapeutic potential of UA is constrained by poor bioavailability. We aimed to improve oral bioavailability of UA by formulating it into biodegradable nanoparticles that use a surface-conjugated ligand targeting the gut-expressed transferrin receptor. Nanoparticle encapsulation of UA led to a sevenfold enhancement in oral bioavailability compared with native UA. Treatment with nanoparticle UA also significantly attenuated the histopathological hallmarks of cisplatin-induced AKI and reduced mortality by 63% in the mouse model. Expression analyses indicated that nanoparticle UA therapy coincided with oxidative stress mitigation and downregulation of nuclear factor erythroid 2-related factor 2- and P53-inducible genes. Additionally, normalization of miRNA (miR-192-5p and miR-140-5p) implicated in AKI, poly(ADP-ribose) polymerase 1 levels, antiapoptotic signaling, intracellular NAD\n                    <jats:sup>+<\/jats:sup>\n                    , and mitochondrial oxidative phosphorylation were observed in the treatment group. Our findings suggest that nanoparticles greatly increase the oral bioavailability of UA, leading to improved survival rates in AKI mice, in part by reducing renal oxidative and apoptotic stress.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00346.2019","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T09:16:21Z","timestamp":1568798181000},"page":"F1255-F1264","source":"Crossref","is-referenced-by-count":58,"title":["Oral delivery of nanoparticle urolithin A normalizes cellular stress and improves survival in mouse model of cisplatin-induced AKI"],"prefix":"10.1152","volume":"317","author":[{"given":"Dianxiong","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu","family":"Ganugula","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Nabity","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sheikh-Hamad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. N. V. Ravi","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5552-09.2010"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2015.01.002"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.01.034"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(86)90687-6"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(86)90687-6"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1021\/jf9025794"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1021\/jf050384i"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-8-31"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/srep38868"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.06.016"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.159"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10040126"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9377-y"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/32.2.140"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.02.010"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2003.10.015"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1021\/acsmacrolett.7b00035"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13816"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b13231"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114510000826"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.242420"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00239.2007"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.120"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111826"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.5.6.703"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.07.086"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2003.00640.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00262.2004"},{"key":"B29","first-page":"1135","volume":"18","author":"Ju SM","year":"2014","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406731102"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08070715"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.09.019"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3644"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011112-140320"},{"key":"B35","first-page":"85","volume":"37","author":"Makris K","year":"2016","journal-title":"Clin Biochem Rev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2112490"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.328"},{"key":"B38","first-page":"243","volume":"34","author":"Nowsheen S","year":"2012","journal-title":"Exp Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/967826"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-079616"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2016.04.065"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007049"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1215-5_24"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2018.1501119"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4132"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/srep29501"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-018-1262-2"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050469"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.11.001"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00081.2005"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000060577.94532.06"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7342"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000042803.28024.92"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2147"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121371"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009030253"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00353.2010"},{"key":"B58","first-page":"594","volume":"295","author":"Xia CQ","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013121270"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2202-5"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013080902"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-016-1485-7"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.12.015"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.173"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00346.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T09:05:08Z","timestamp":1573117508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00346.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,1]]},"references-count":64,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,11,1]]}},"alternative-id":["10.1152\/ajprenal.00346.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00346.2019","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,1]]}}}