Targeting Oct2 and P53: Formononetin prevents cisplatin-induced acute kidney injury

被引：49

作者：

Huang, Di ^{[1
]}

Wang, Chuangyuan ^{[1
,2
]}

Duan, Yingjie ^{[3
]}

Meng, Qiang ^{[1
,2
]}

Liu, Zhihao ^{[1
,2
]}

Huo, Xiaokui ^{[1
,2
]}

Sun, Huijun ^{[1
,2
]}

Ma, Xiaodong ^{[1
,2
]}

Liu, Kexin ^{[1
,2
]}

机构：

[1] Dalian Med Univ, Coll Pharm, Dept Clin Pharmacol, 9 West Sect,Lvshun South Rd, Dalian 116044, Peoples R China

[2] Prov Key Lab Pharmacokinet & Transport, Dalian, Liaoning, Peoples R China

[3] Fuxin Min Grp Co Ltd, Gen Hosp, Fuxin, Liaoning, Peoples R China

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 2017年 / 326卷

基金：

中国国家自然科学基金;

关键词：

Cisplatin; Regeneration; Apoptosis; Oct2; p53; ACUTE-RENAL-FAILURE; ARISTOLOCHIC ACID; EPITHELIAL-CELLS; NEPHROTOXICITY; REPAIR; EXPRESSION; MECHANISMS; PATHOPHYSIOLOGY; REGENERATION; JBP485;

D O I：

10.1016/j.taap.2017.04.013

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Nephrotoxicity is one of major side effects of cisplatin in chemotherapy. Therefore, there is an urgent medical need to develop drugs that may protect kidney from toxicity. In previous study, we found that it showed the protective effects of formononetin against apoptosis by upregulating Nrf2. In this study, we investigated the renoprotective effect of formononetin against cisplatin-induced AKI and tried to elucidate the possible mechanisms. The amelioration of renal function, histopathological changes, and apoptosis in tubular cells was observed after formononetin treatment. Formononetin decreased expression of organic cation transporter 2 (Oct2) and increased the expressions of multidrug resistance-associated proteins (Mrps), which might result in a decrease accumulation of cisplatin in tubular cells after AKI. 5-Bromo-2-deoxyuridine (BrdU) and Ki-67 staining assay indicated that formononetin could promote the renal tubular cells proliferation after cisplatin nephrotoxicity. Moreover, formononetin regulated cyclins and pro-apoptotic proteins to involve the regulation of cell cycle. Furthermore, formononetin decreased p53 expression via promoting the overexpression of murine double minute 2 (MDM2) and MDMX. Taken together, formononetin provided protective effects by promoting proliferation of surviving renal tubular cells and inhibiting apoptosis after cisplatin-induced AKI. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：15 / 24

页数：10

共 38 条

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