Esteban-Fernández D, Verdaguer J M, Ramírez-Camacho R, Palacios M A, Gómez-Gómez M M
Department of Analytical Chemistry, University Complutense of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
J Anal Toxicol. 2008 Mar;32(2):140-6. doi: 10.1093/jat/32.2.140.
Antitumoral Pt-containing drugs present side effects like nephrotoxicity and ototoxicity. Several systematic experiments have been carried out with Wistar rats treated with cisplatin, carboplatin, and oxaliplatin to study Pt-drugs accumulation and elimination, and Pt-biomolecule distribution in the cells and cytosols of ear, kidney, and liver. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis shows a cisplatin accumulation capability between oxaliplatin (the highest) and carboplatin (the lowest). The maximum concentration of Pt in all the organs studied was achieved around the first week after cisplatin treatment. During the first 30 days, the elimination was very fast, decreasing in the subsequent 60 days in all the organs. Analysis of cytosols by liquid chromatography (LC)-ICP-MS showed an analogous behavior. In most samples, the distribution of the three drugs in the cellular and cytosolic fractions was similar for all the tissues. For kidney and ear, approximately 60% and 30%, respectively, of the metal accumulated was present in the cytosol, the cytosolic fractions smaller than 50 KDa being especially important. Cisplatin-biomolecule interaction strength under denaturing conditions was evaluated by LC-ICP-MS and showed a quite strong bond.
含铂抗肿瘤药物存在肾毒性和耳毒性等副作用。已对用顺铂、卡铂和奥沙利铂治疗的Wistar大鼠进行了多项系统实验，以研究铂类药物的积累和消除，以及铂在耳、肾和肝脏细胞及胞质溶胶中的生物分子分布。电感耦合等离子体质谱（ICP-MS）分析表明，奥沙利铂（最高）和顺铂之间的积累能力高于卡铂（最低）。在顺铂治疗后的第一周左右，在所研究的所有器官中均达到铂的最高浓度。在最初的30天内，消除速度非常快，在随后的60天内所有器官中的铂浓度均下降。通过液相色谱（LC）-ICP-MS对胞质溶胶进行分析，结果显示出类似的行为。在大多数样品中，所有组织中三种药物在细胞和胞质组分中的分布相似。对于肾脏和耳朵，分别约60%和30%的积累金属存在于胞质溶胶中，小于50 kDa的胞质组分尤为重要。通过LC-ICP-MS评估了变性条件下顺铂与生物分子的相互作用强度，结果显示二者结合相当牢固。
