Protective effect of Rhein against vancomycin-induced nephrotoxicity through regulating renal transporters and Nrf2 pathway.

Publisher: Wiley Country of Publication: England NLM ID: 8904486 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1573 (Electronic) Linking ISSN: 0951418X NLM ISO Abbreviation: Phytother Res Subsets: MEDLINE

Publication: : Chichester : Wiley
Original Publication: London : Heyden & Son, c1987-

Vancomycin*/pharmacology ; NF-E2-Related Factor 2*/metabolism; Rats ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism ; Kidney ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Oxidative Stress ; Mammals/metabolism

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-induced nephrotoxicity (VIN). VIN models were established in rats and NRK-52E cells. Rhein up-regulated the expressions of renal organic anion transporter (Oat) 1, Oat3, organic cation transporter 2 (Oct2), multidrug resistance-associated protein 2 (Mrp2), mammal multidrug and toxin extrusion proteins 1 (Mate 1) and P-glycoprotein (P-gp) to facilitate the efflux of plasma creatinine, blood urea nitrogen (BUN), and plasma indoxyl sulfate. Rhein increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) to regulate the expression of Mrp2, P-gp, 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-cell lymphoma-2 (Bcl-2) and decreased expressions of Bcl-2-like 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-Nrf2 interaction. Rhein ameliorated VIN mainly through regulating the expressions of renal transporters and acting on Nrf2 pathway.
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82003837 National Natural Science Foundation of China

Keywords: Nrf2; Rhein; renal protection; renal transporter; vancomycin-induced nephrotoxicity

6Q205EH1VU (Vancomycin)
0 (Kelch-Like ECH-Associated Protein 1)
0 (NF-E2-Related Factor 2)
YM64C2P6UX (rhein)
0 (Proto-Oncogene Proteins c-bcl-2)

Date Created: 20220712 Date Completed: 20221118 Latest Revision: 20221118

20240105

10.1002/ptr.7559

35820659