Puerarin improves methotrexate-induced renal damage by up-regulating renal expression of Oat1 and Oat3 in vivo and in vitro

Publication date: July 2018 Source:Biomedicine & Pharmacotherapy, Volume 103 Author(s): Qi Liu, Zhihao Liu, Xiaokui Huo, Changyuan Wang, Qiang Meng, Huijun Sun, Pengyuan Sun, Jinyong Peng, Xiaodong Ma, Kexin Liu The regulation of renal transporters such as organic anion transporter (OATs) is a new target for treatment of acute renal failure. The purpose of this study was to investigate whether the effect of puerarin (Pur) on renal damage induced by methotrexate (MTX) is related to the expression of renal Oat1/3 in vivo and in vitro, and to explore the related mechanisms. Effect of Pur on the renal damage caused by MTX was evaluated by assessment of the changes of endogenous metabolites, toxins and H&E staining. Furthermore, Real-time PCR and western blot methods were taken to evaluate the modulation of Oat1/3 in rats. Then, the regulation of Oat1/3 by B-cell CLL/lymphoma (BCL)6 was explored by siRNA assay using NRK-52E cells in vitro. Pur reduced levels of endogenous metabolites and toxins, like creatinine, urea nitrogen and indoxyl sulfate in plasma in MTX-treated rats. Moreover, plasma concentration of MTX was significantly decreased, while the cumulative urinary excretion of MTX and the uptake of MTX by kidney slices were strongly increased after administration of multiple-dose of Pur via up-regulation of renal Oat1/3 expression. Knockdown of BCL6 by siRNA abrogated the Pur-induced Oat1/3 expression in NRK-52E cells. Pur improved MTX-induced ren...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research