A novel preventive mechanism of gentamicin-induced nephrotoxicity by atorvastatin

Mei Chun Lee, Kuei Ju Cheng, Shih Ming Chen, Yi Chieh Li, Kazuhiro Imai, Chun Ming Lee, Jen Ai Lee

研究成果: 雜誌貢獻文章同行評審

7 引文 斯高帕斯(Scopus)


Atorvastatin (ATO) inhibits the synthesis of nonsteroidal isoprenoid compounds and possesses a pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)-induced renal injury remains obscure. Although underlying multifaceted mechanisms involving GM-induced nephrotoxicity were well known, further work on elucidating the essential mechanism was needed. Using a fluorogenic derivatization–liquid chromatography tandem mass spectrometry proteomic method (FD-LC–MS/MS method), we investigated the effects and mechanisms of ATO treatment on GM-induced 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 PPARα. The proteins involved in GM nephrotoxicity were sodium–hydrogen 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 (P-value<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-induced nephrotoxicity biomarkers such as CTSV and transthyretin.

頁(從 - 到)e4639
期刊Biomedical Chromatography
出版狀態已發佈 - 11月 1 2019

ASJC Scopus subject areas

  • 分析化學
  • 生物化學
  • 分子生物學
  • 藥理
  • 藥物發現
  • 臨床生物化學


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