title: High-resolution laser ablation-inductively coupled plasma-mass spectrometry imaging of cisplatin-induced nephrotoxic side effects.
abstract: Two-dimensional elemental mapping (bioimaging) via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was performed on 5 μm thick formalin-fixed, paraffin-embedded kidney tissue sections from Cynomolgus monkeys administered with increasing pharmacological doses of cisplatin. Laterally resolved pixels of 1 μm were achieved, enabling elemental analysis on a (sub-)cellular level. Zones of high Pt response were observed in the renal cortex, where proximal tubules are present, the epithelium of which is responsible for partial reabsorption of cisplatin. Histopathological evaluation, of hematoxylin and eosin-stained serial sections, adjacent to the sections probed via LA-ICP-MS, revealed minimal to mild cisplatin-related lesions (<100 μm) in the renal cortex. Necrotic proximal tubules with sloughed epithelial cells in their lumen could be linked directly to the areas with the highest accumulation of cisplatin, indicating a direct link between cellular concentration and toxicity, thereby providing more insight into the mechanisms through which renal damage occurs.
authors.affiliation: Department of Analytical Chemistry, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Van Acker
authors.affiliation: Department of Analytical Chemistry, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium.
authors.forename: Stijn J M
authors.initials: SJ
authors.lastname: Van Malderen
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Van Heerden
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, 3210 Merryfield Row, San Diego, CA, 92121, USA.
authors.forename: James Eric
authors.initials: JE
authors.lastname: McDuffie
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Cuyckens
authors.affiliation: Department of Analytical Chemistry, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium. Electronic address: Frank.Vanhaecke@UGent.be.
authors.forename: Frank
authors.initials: F
authors.lastname: Vanhaecke
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002138:Calibration; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D007668:Kidney / Q000187:drug effects*; D053685:Laser Therapy / Q000379:methods*; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Cisplatin; High-resolution; Kidney; LA-ICP-MS; Mass spectrometry imaging