Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, C/Julian Clavería 8, 33006 Oviedo, Spain.
Chem Res Toxicol. 2011 Jun 20;24(6):896-904. doi: 10.1021/tx200085n. Epub 2011 May 3.
Cisplatin is one of the most effective chemotherapeutic agents, although its clinical use is limited by severe renal toxicity. This toxicity seems to be related to the accumulation of the drug in kidney tissues, leading to renal failure. For this reason, several compounds have been evaluated to ameliorate the nephrotoxicity induced by cisplatin. In the present investigation, we report the effect of the oral administration of selenomethionine before intraperitoneal cisplatin treatment. The preadministration of this Se species has been shown to have an important effect in reducing renal damage induced by cisplatin by increasing the excreted urea and improving creatinine clearance. Quantification of the level of DNA--cisplatin adducts in kidney and liver tissues was carried out by postcolumn isotope dilution analysis using liquid chromatography-inductively coupled plasma (LC-ICP-MS) as speciation set up. The level of DNA--cisplatin adducts in rats given Se-methionine in the drinking water before cisplatin administration was considerably lower in kidney tissues with respect to the animals drinking only water. Such effects were not observed in liver tissue. Initial speciation studies of Pt and Se conducted in kidney tissues of exposed animals by HPLC-ICP-MS have revealed the presence of cisplatin as part of a complex with Se-methionine, which can be eventually excreted into urine. This Pt--Se complex could explain the observed reduction of the kidney damage in Se-methionine-treated animals.
顺铂是最有效的化疗药物之一，尽管其临床应用受到严重肾毒性的限制。这种毒性似乎与药物在肾脏组织中的积累有关，导致肾衰竭。出于这个原因，已经评估了几种化合物来改善顺铂引起的肾毒性。在本研究中，我们报告了顺铂腹腔内给药前口服硒蛋氨酸的效果。这种硒物种的预先给药已被证明通过增加排泄的尿素和改善肌酐清除率对减少顺铂引起的肾损伤有重要作用。通过使用液体色谱-电感耦合等离子体质谱（LC-ICP-MS）作为形态分析建立的柱后同位素稀释分析，对肾和肝组织中 DNA-顺铂加合物的水平进行了定量。与仅饮水的动物相比，在给予顺铂前在饮用水中给予硒蛋氨酸的大鼠肾组织中的 DNA-顺铂加合物水平显着降低。在肝组织中未观察到这种作用。通过高效液相色谱-电感耦合等离子体质谱（HPLC-ICP-MS）对暴露动物肾组织中进行的初始 Pt 和 Se 形态研究表明，顺铂作为与硒蛋氨酸的复合物存在，最终可随尿液排出。这种 Pt-Se 复合物可以解释在硒蛋氨酸处理的动物中观察到的肾损伤减少。
