A novel preventive mechanism of gentamicin‐induced nephrotoxicity by atorvastatin. (7th August 2019)

• Record Type: Journal Article
• Authors: Lee, Mei‐Chun; Cheng, Kuei‐Ju; Chen, Shih‐Ming; Li, Yi‐Chieh; Imai, Kazuhiro; Lee, Chun‐Ming; Lee, Jen‐Ai
• Is Part Of: Biomedical chromatography. Volume 33:Number 11(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-08-07
• Subjects: atorvastatin -- DAABD‐cl -- gentamicin -- nephrotoxicity; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.4639
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: 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 PPAR α . 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.