Moraleja Irene, Esteban-Fernández Diego, Lázaro Alberto, Humanes Blanca, Neumann Boris, Tejedor Alberto, Luz Mena M, Jakubowski Norbert, Gómez-Gómez M Milagros
Analytical Chemistry Department, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.
BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str.11, 12489, Berlin, Germany.
Anal Bioanal Chem. 2016 Mar;408(9):2309-18. doi: 10.1007/s00216-016-9327-0. Epub 2016 Jan 29.
The study of the distribution of the cytostatic drugs cisplatin, carboplatin, and oxaliplatin along the kidney may help to understand their different nephrotoxic behavior. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) allows the acquisition of trace element images in biological tissues. However, results obtained are affected by several variations concerning the sample matrix and instrumental drifts. In this work, an internal standardization method based on printing an Ir-spiked ink onto the surface of the sample has been developed to evaluate the different distributions and accumulation levels of the aforementioned drugs along the kidney of a rat model. A conventional ink-jet printer was used to print fresh sagittal kidney tissue slices of 4 μm. A reproducible and homogenous deposition of the ink along the tissue was observed. The ink was partially absorbed on top of the tissue. Thus, this approach provides a pseudo-internal standardization, due to the fact that the ablation sample and internal standard take place subsequently and not simultaneously. A satisfactory normalization of LA-ICP-MS bioimages and therefore a reliable comparison of the kidney treated with different Pt-based drugs were achieved even for tissues analyzed on different days. Due to the complete ablation of the sample, the transport of the ablated internal standard and tissue to the inductively coupled plasma-mass spectrometry (ICP-MS) is practically taking place at the same time. Pt accumulation in the kidney was observed in accordance to the dosages administered for each drug. Although the accumulation rate of cisplatin and oxaliplatin is high in both cases, their Pt distributions differ. The strong nephrotoxicity observed for cisplatin and the absence of such side effect in the case of oxaliplatin could explain these distribution differences. The homogeneous distribution of oxaliplatin in the cortical and medullar areas could be related with its higher affinity for cellular transporters such as MATE2-k.
研究细胞毒性药物顺铂、卡铂和奥沙利铂在肾脏中的分布情况，可能有助于理解它们不同的肾毒性行为。激光烧蚀电感耦合等离子体质谱法（LA-ICP-MS）可获取生物组织中的微量元素图像。然而，所获得的结果会受到与样品基质和仪器漂移有关的多种变化的影响。在这项工作中，已开发出一种基于将掺入铱的墨水打印在样品表面的内标法，以评估上述药物在大鼠模型肾脏中的不同分布和积累水平。使用传统的喷墨打印机打印4μm厚的新鲜肾脏矢状切片。观察到墨水沿组织的沉积具有可重复性且均匀。墨水部分被组织表面吸收。因此，由于烧蚀样品和内标随后而非同时进行，这种方法提供了一种伪内标法。即使对于在不同日期分析的组织，也实现了LA-ICP-MS生物图像的令人满意的归一化，从而能够可靠地比较用不同铂类药物处理的肾脏。由于样品被完全烧蚀，烧蚀的内标和组织向电感耦合等离子体质谱仪（ICP-MS）的传输实际上是同时进行的。观察到肾脏中的铂积累与每种药物的给药剂量一致。尽管顺铂和奥沙利铂在两种情况下的积累率都很高，但它们的铂分布不同。顺铂观察到的强烈肾毒性以及奥沙利铂不存在这种副作用可以解释这些分布差异。奥沙利铂在皮质和髓质区域的均匀分布可能与其对细胞转运体如MATE2-k的更高亲和力有关。
