{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:21Z","timestamp":1792003701031,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T00:00:00Z","timestamp":1565136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Taipei Medical University-Wan Fang Hospital","award":["102TMU-WFH-12"],"award-info":[{"award-number":["102TMU-WFH-12"]}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Atorvastatin (ATO) inhibits the synthesis of nonsteroidal isoprenoid compounds and possesses a pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)\u2010induced renal injury remains obscure. Although underlying multifaceted mechanisms involving GM\u2010induced nephrotoxicity were well known, further work on elucidating the essential mechanism was needed. Using a fluorogenic derivatization\u2013liquid chromatography tandem mass spectrometry proteomic method (FD\u2010LC\u2013MS\/MS method), we investigated the effects and mechanisms of ATO treatment on GM\u2010induced nephrotoxicity in rats. Consequently, 49 differentially expressed proteins were identified. The most significant mechanisms of nephrotoxicity caused by GM were mitochondrial dysfunction, fatty acid metabolism and oxidative stress. Their upstream regulator was found to be PPAR<jats:italic>\u03b1<\/jats:italic>. The proteins involved in GM nephrotoxicity were sodium\u2013hydrogen exchanger regulatory factor (SLC9A3R1), cathepsin V (CTSV), macrophage migration inhibitory factor (MIF) and RhoGDP dissociation inhibitor alpha (ARHGDIA). After ATO intervention, we observed a reversed enrichment pattern of their expression, especially in CTSV and SLC9A3R1 (<jats:italic>P<\/jats:italic>\u2010value&lt;0.05). We predicted that ATO may improve abnormal phospholipid metabolism and phospholipidosis caused by GM and also alleviate cell volume homeostasis and reverse the interference of GM with the transporter. Furthermore, proteomic results also provided clues as to GM\u2010induced nephrotoxicity biomarkers such as CTSV and transthyretin.<\/jats:p>","DOI":"10.1002\/bmc.4639","type":"journal-article","created":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T21:53:05Z","timestamp":1561845185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel preventive mechanism of gentamicin\u2010induced nephrotoxicity by atorvastatin"],"prefix":"10.1002","volume":"33","author":[{"given":"Mei\u2010Chun","family":"Lee","sequence":"first","affiliation":[{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"},{"name":"Department of Pharmacy MacKay Memorial Hospital  Taipei Taiwan"},{"name":"Mackay Junior College of Medicine Nursing, and Management  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuei\u2010Ju","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"},{"name":"Wan Fang Hospital Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-4847","authenticated-orcid":false,"given":"Shih\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chieh","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Imai","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences Musashino University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Mackay Junior College of Medicine Nursing, and Management  Taipei Taiwan"},{"name":"Department of Internal Medicine St. Joseph's Hospital  Yunlin County Taiwan"},{"name":"Division of Infectious Disease, Department of Internal Medicine MacKay Memorial Hospital  Taipei Taiwan"},{"name":"MacKay Medical College  New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-8736","authenticated-orcid":false,"given":"Jen\u2010Ai","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(03)00186-8"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.09.021"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.305.6866.1421"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.04.004"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.10.015"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050104"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000143319.73503.38"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.231"},{"key":"e_1_2_5_10_1","first-page":"694","article-title":"Chronic tubulointerstitial nephritis and renal insufficiency associated with long\u2010term \"subtherapeutic\" gentamicin","volume":"112","author":"Houghton D. 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