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.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044, China. liutaomedical@qq.com
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Xinjin
authors.initials: X
authors.lastname: Guo
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
authors.forename: Taiichi
authors.initials: T
authors.lastname: Kaku
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D015227:Lipid Peroxidation; D015394:Molecular Structure; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D010130:p-Aminohippuric Acid / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; C412308:JBP 485; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C421043:Slc22a6 protein, rat; C114338:organic anion transport protein 3; D002945:Cisplatin; D010130:p-Aminohippuric Acid