Magnesium attenuates cisplatin-induced nephrotoxicity by regulating the expression of renal transporters

European Journal of Pharmacology
Yoshitaka SaitoKen Iseki

Abstract

Cisplatin (CDDP)-induced nephrotoxicity (CIN) is one of the most serious toxicities caused by this potent antitumor agent. It has been reported that Mg premedication attenuates CIN in clinical trials; however, the mechanism underlying its nephroprotection is not fully understood. Therefore, the aim of this study was to determine whether Mg administration affects CDDP accumulation by regulating the expression level of renal transporters. Rats were divided into control, Mg (40mg/kg) alone, 2.5mg/kg CDDP with (20 and 40mg/kg) and without Mg, 5mg/kg CDDP groups. These substances were administered on the same day and 7 days later their kidneys were removed. The expression levels of renal transporters and platinum (Pt) accumulation were analyzed. The serum creatinine level was significantly increased by CDDP administration and treatment with Mg significantly ameliorated such elevation. The expressions of the renal organic cation transporter 2 (rOct2) and renal multidrug and toxin extrusion protein 1 (rMate1) were downregulated and upregulated, respectively following co-administration with Mg, which significantly reduced the renal Pt accumulation in the 2.5mg/kg CDDP-treated group. Moreover, Mg dose-dependently downregulated rOct2, no...Continue Reading

Citations

Mar 3, 2018·International Journal of Molecular Sciences·Juan R Muñoz-CastañedaMaría E Rodríguez-Ortiz
Jun 23, 2019·International Journal of Molecular Sciences·Sara J HolditchCharles L Edelstein
Oct 16, 2018·Frontiers in Pharmacology·Zulfan ZazuliAnke-Hilse Maitland-van der Zee
Dec 4, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshitaka Saito
Jul 20, 2021·Pharmacology Research & Perspectives·George LiamisHaralampos Milionis
Aug 2, 2021·European Journal of Pharmacology·Keisuke OkamotoMasaki Kobayashi
Aug 8, 2021·International Journal of Molecular Sciences·Robert CzarnomysyKrzysztof Bielawski

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