{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:52Z","timestamp":1791919072888,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003837"],"award-info":[{"award-number":["82003837"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vancomycin (VCM)'s nephrotoxicity limits its application and therapeutic efficiency. The aim of this study was to determine the protective effect of rhein against VCM\u2010induced nephrotoxicity (VIN). VIN models were established in rats and NRK\u201052E cells. Rhein up\u2010regulated the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance\u2010associated protein 2 (Mrp2), mammal multidrug and toxin extrusion proteins 1 (Mate 1) and P\u2010glycoprotein (P\u2010gp) to facilitate the efflux of plasma creatinine, blood urea nitrogen (BUN), and plasma indoxyl sulfate. Rhein increased the expression of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) to regulate the expression of Mrp2, P\u2010gp, and Mate 1. The increased level of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) and reduced number of apoptosis cells were observed after treatment of rhein. Rhein decreased the number of apoptosis cells as well as increased the expression of B\u2010cell lymphoma\u20102 (Bcl\u20102) and decreased expressions of Bcl\u20102\u2010like protein 4 (Bax). ML385, as a typical inhibitor of Nrf2, reversed the protective effects of rhein in cells. Rhein oriented itself in the site of Keap1, inhibiting the Keap1\u2013Nrf2 interaction. Rhein ameliorated VIN mainly through regulating the expressions of renal transporters and acting on Nrf2 pathway.<\/jats:p>","DOI":"10.1002\/ptr.7559","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T19:40:04Z","timestamp":1657654804000},"page":"4244-4262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Protective effect of Rhein against vancomycin\u2010induced nephrotoxicity through regulating renal transporters and Nrf2 pathway"],"prefix":"10.1002","volume":"36","author":[{"given":"Yanna","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Dalian Medical University  Dalian China"},{"name":"Department of Clinical Pharmacology, College of Pharmacy Dalian Medical University  Dalian 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