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Title: Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

Abstract

The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expressionmore » of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.« less

Authors:
 [1];  [1];  [2];  [1];  [2];  [1];  [2];  [1];  [1];  [2];  [1];  [2];
  1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China)
  2. (China)
Publication Date:
OSTI Identifier:
22215963
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARGON FLUORIDES; BLOOD; KIDNEYS; MESSENGER-RNA; NITROGEN; POLYCYCLIC AROMATIC HYDROCARBONS; POLYMERASE CHAIN REACTION; RATS; SERINE; SUPEROXIDE DISMUTASE; TOXINS; UREA

Citation Formats

Liu, Tao, E-mail: liutaomedical@qq.com, Meng, Qiang, E-mail: mengq531@yahoo.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Wang, Changyuan, E-mail: wangcyuan@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Liu, Qi, E-mail: llaqii@yahoo.com.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Guo, Xinjin, E-mail: guo.xinjin@163.com, Sun, Huijun, E-mail: sunhuijun@hotmail.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Peng, Jinyong, E-mail: jinyongpeng2005@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, and and others. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.019.
Liu, Tao, E-mail: liutaomedical@qq.com, Meng, Qiang, E-mail: mengq531@yahoo.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Wang, Changyuan, E-mail: wangcyuan@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Liu, Qi, E-mail: llaqii@yahoo.com.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Guo, Xinjin, E-mail: guo.xinjin@163.com, Sun, Huijun, E-mail: sunhuijun@hotmail.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Peng, Jinyong, E-mail: jinyongpeng2005@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, & and others. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats. United States. doi:10.1016/J.TAAP.2012.08.019.
Liu, Tao, E-mail: liutaomedical@qq.com, Meng, Qiang, E-mail: mengq531@yahoo.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Wang, Changyuan, E-mail: wangcyuan@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Liu, Qi, E-mail: llaqii@yahoo.com.cn, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Guo, Xinjin, E-mail: guo.xinjin@163.com, Sun, Huijun, E-mail: sunhuijun@hotmail.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Peng, Jinyong, E-mail: jinyongpeng2005@163.com, Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, and and others. Thu . "Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats". United States. doi:10.1016/J.TAAP.2012.08.019.
@article{osti_22215963,
title = {Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats},
author = {Liu, Tao, E-mail: liutaomedical@qq.com and Meng, Qiang, E-mail: mengq531@yahoo.cn and Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University and Wang, Changyuan, E-mail: wangcyuan@163.com and Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University and Liu, Qi, E-mail: llaqii@yahoo.com.cn and Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University and Guo, Xinjin, E-mail: guo.xinjin@163.com and Sun, Huijun, E-mail: sunhuijun@hotmail.com and Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University and Peng, Jinyong, E-mail: jinyongpeng2005@163.com and Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University and and others},
abstractNote = {The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.},
doi = {10.1016/J.TAAP.2012.08.019},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 264,
place = {United States},
year = {2012},
month = {11}
}