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番茄红素对顺铂诱导的大鼠急性肾损伤的影响:有机阴离子和阳离子转运体评估

Effect of lycopene against cisplatin-induced acute renal injury in rats: organic anion and cation transporters evaluation.

作者信息

Erman Fazilet, Tuzcu Mehmet, Orhan Cemal, Sahin Nurhan, Sahin Kazim

机构信息

Elazig Health High School, Firat University, Elazig, 23119, Turkey.

出版信息

Biol Trace Elem Res. 2014 Apr;158(1):90-5. doi: 10.1007/s12011-014-9914-x. Epub 2014 Feb 16.

Abstract

In the present study, we investigated the effects of lycopene on the expression of organic anion transporters (OATs), organic cation transporters (OCTs), and multidrug resistance-associated proteins (MRPs) of cisplatin-induced nephrotoxicity in rats. Twenty-eight 8-week-old Wistar rats were divided into four groups: control, lycopene-treated (6 mg/kg BW by oral gavage), cisplatin-treated (7 mg/kg BW, IP), and lycopene in combination with cisplatin-treated groups. In the presence of cisplatin, serum urea nitrogen (urea-N) (48.5 vs. 124.3 mg/dl) and creatinine (0.29 vs. 1.37 mg/dl) levels and the kidney efflux transporters MRP2 and MRP4 levels were significantly increased, whereas OAT1, OAT3, OCT1, and OCT2 levels in kidney were decreased in the treated rats compared with normal control rats. However, administration of lycopene in combination with cisplatin resulted in a reduction in the serum urea-N (124.3 vs. 62.4) and creatinine (1.37 vs. 0.40) levels and the kidney efflux transporters MRP2 and MRP4 proteins in the kidneys. Administration of lycopene to acute renal injury-induced rats largely upregulated the organic anion transporters (OAT1 and 3) and organic cation transporters (OCT1 and 2) to decrease the side effects of cisplatin. The present study suggests that lycopene synergizes with its nephroprotective effect against cisplatin-induced acute kidney injury in rats.

摘要

在本研究中,我们调查了番茄红素对顺铂诱导的大鼠肾毒性中有机阴离子转运体(OATs)、有机阳离子转运体(OCTs)和多药耐药相关蛋白(MRPs)表达的影响。28只8周龄的Wistar大鼠被分为四组:对照组、番茄红素处理组(经口灌胃给予6 mg/kg体重)、顺铂处理组(腹腔注射7 mg/kg体重)和番茄红素与顺铂联合处理组。在存在顺铂的情况下,血清尿素氮(尿素-N)水平(48.5对124.3 mg/dl)和肌酐水平(0.29对1.37 mg/dl)以及肾外排转运体MRP2和MRP4水平显著升高,而与正常对照大鼠相比,处理组大鼠肾脏中的OAT1、OAT3、OCT1和OCT2水平降低。然而,番茄红素与顺铂联合给药导致血清尿素-N水平(124.3对62.4)和肌酐水平(1.37对0.40)以及肾脏中肾外排转运体MRP2和MRP4蛋白减少。给急性肾损伤诱导的大鼠施用番茄红素在很大程度上上调了有机阴离子转运体(OAT1和3)和有机阳离子转运体(OCT1和2),以减少顺铂的副作用。本研究表明,番茄红素对顺铂诱导的大鼠急性肾损伤具有协同肾保护作用。

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