Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.
Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.
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DOI：
10.1021/acs.chemrestox.5b00176
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发表时间：
2015-08
影响因子：
4.1
通讯作者：
R. Bulacio;N. Anzai;M. Ouchi;A. Torres
中科院分区：
文献类型：
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作者：
R. Bulacio;N. Anzai;M. Ouchi;A. Torres
顺铂是一种常用的化疗药物。其主要副作用是肾毒性。据报告，有机阴离子转运蛋白5（Oat 5）尿排泄升高，表明肾脏扰动，而在顺铂诱导的急性肾损伤（阿基）中仍未观察到传统肾损伤标志物的变化。还证明了Oat 5通过外泌体途径在尿液中排泄。本研究旨在证明外泌体Oat 5的尿排泄对肾损伤的特异性反应，与其他顺铂毒性作用无关，以加强Oat 5尿水平作为阿基的特异性生物标志物。为了实现这一目标，我们评估了当顺铂肾损伤通过肾脏保护化合物N-乙酰半胱氨酸的共同给药来预防时，外泌体Oat 5的尿排泄是否恢复到其基础水平。顺铂给药后4天，在顺铂给药的雄性Wistar大鼠（Cis组）中诱导阿基，因为其通过尿素和肌酐血浆水平升高得到证实。还观察到肾小管损伤。在联合治疗的动物（Cis + NAC组）中，血浆尿素和肌酐浓度趋于恢复至其基础值，肾小管损伤得到改善。在Cis组中，外泌体Oat 5的尿排泄显著增加，但是当通过N-乙酰半胱氨酸共同给药改善肾损伤时，未检测到这种增加。因此，在这项工作中，我们观察到只有在产生肾损伤时，外泌体Oat 5的尿排泄才会增加，这证明了其作为肾损伤生物标志物的特异性。
Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.