Abstract

The main dose-limiting side effect of cisplatin is nephrotoxicity. The utilization of cisplatin is an issue of balancing tumour toxicity versus platinum-induced nephrotoxicity. In this study, we focused on intraorgan distribution of common essential trace elements zinc, copper, and iron in healthy mouse kidneys and distribution of platinum after cisplatin treatment. Renal distribution in 12 nontreated Nu-Nu mice (males) was assessed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Furthermore, 9 Nu-Nu mice were treated with cisplatin. The order of elements concentration in kidneys was as follows: Fe > Zn > Cu. All three metals showed the higher concentrations at the cortex and medulla (28.60, 3.35, and 93.83 μg/g for Zn, Cu, and Fe, respectively) and lower concentration at the pelvis and the urinary tract (20.20, 1.93, and 62.48 μg/g for Zn, Cu, and Fe, respectively). No statistically significant difference between cortex and medulla was observed for these elements. After platinum treatment, the concentration of platinum in kidneys was enhanced more than 60-times, p < 0.001. Platinum significantly showed the highest accumulation in cortex (2.11 μg/g) with a gradient distribution. Platinum was less accumulated in medulla and pelvis than in cortex, and the lowest accumulation occurred in the urinary tract (1.13 μg/g). Image processing has been successfully utilized to colocalize metal distribution using LA-ICP-MS and histological samples images.

Highlights

  • Some metals are essential for cell homeostasis

  • We focused on the intraorgan distribution of zinc, copper, and iron in healthy mouse kidneys and distribution of platinum after cisplatin treatment by using LA-ICP-MS combined with routine microscopic techniques

  • Regardless of considerable efforts to discover less-toxic alternatives, cisplatin is still widely prescribed in clinical practice

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Summary

Introduction

Iron, and copper are common essential elements and participate in the regulation of numerous physiological processes such as protein synthesis, enzymatic reactions, and antioxidant defences. These metals are useful at very low concentrations but can be toxic in larger amounts or certain forms [1]. The method of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a useful tool for determination of element distribution in various samples It has been utilized for quantitative imaging of platinum group elements in tumor spheroids [10], determination of cisplatin retention in cochlea after chemotherapy [11], or for quantification of the interactions of platinum compound with human serum albumin [12]. Metal distribution maps obtained using LA-ICP-MS and histological samples images of the organ were correlated via the utilization of image processing

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