Elemental Bioimaging in Kidney by LA–ICP–MS As a Tool to Study Nephrotoxicity and Renal Protective Strategies in Cisplatin Therapies

• Published in: Analytical chemistry (Washington) Vol. 83; no. 20; pp. 7933 - 7940
• Main Authors: Moreno-Gordaliza, Estefanía, Giesen, Charlotte, Lázaro, Alberto, Esteban-Fernández, Diego, Humanes, Blanca, Cañas, Benito, Panne, Ulrich, Tejedor, Alberto, Jakubowski, Norbert, Gómez-Gómez, M. Milagros
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.10.2011
• Subjects: Analytical chemistry; Animals; Antineoplastic Agents - toxicity; Biochemistry; Biological and medical sciences; Cells; Chemistry; Cilastatin - pharmacology; Cisplatin - toxicity; Copper - chemistry; Exact sciences and technology; Female; Kidney - pathology; Kidney Cortex - pathology; Kidney Tubules, Proximal - pathology; Mass spectrometry; Mass Spectrometry - instrumentation; Mass Spectrometry - methods; Medical sciences; Nephrology. Urinary tract diseases; Platinum; Platinum - analysis; Rats; Rats, Wistar; Spectrometric and optical methods; Tissues; Tumors of the urinary system; Zinc - chemistry; Rat; Metal; Inductive coupling plasma spectrometry; Kidney; Tissue; Platinum; Imaging; Detection limit; Serum; Tool; Urine; Coupled method; Estimation; Rodentia; Cisplatin; Vertebrata; Sensitivity; Mammalia; Detector; Reproducibility; Distribution; Parameter; Strategy; Laser ablation technique; Nephrotoxicity; Mass spectrometry
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/ac201933x

A laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS)-based methodology is presented for Pt, Cu, and Zn bioimaging on whole kidney 3 μm sagittal sections from rats treated with pharmacological doses of cisplatin, which were sacrificed once renal damage had taken place. Pt turned out to accumulate in the kidney cortex and corticomedullary junction, corresponding to areas where the proximal tubule S3 segments (the most sensitive cells to cisplatin nephrotoxicity) are located. This demonstrates the connection between platinum accumulation and renal damage proved by histological examination of HE-stained sections and evaluation of serum and urine biochemical parameters. Cu and Zn distribution maps revealed a significant displacement in cells by Pt, as compared to control tissues. A dramatic decrease in the Pt accumulation in the cortex was observed when cilastatin was coadministered with cisplatin, which can be related to its nephroprotective effect. Excellent imaging reproducibility, sensitivity (LOD 50 fg), and resolution (down to 8 μm) were achieved, demonstrating that LA–ICP–MS can be applied as a microscopic metal detector at cellular level in certain tissues. A simple and quick approach for the estimation of Pt tissue levels was proposed, based on tissue spiking.