How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs? An investigation combining ?XRF and statistical analysis: Part I: On mice - 25/04/16

Doi : 10.1016/j.crci.2016.03.014

Emmanuel Estève ^a, Dominique Bazin ^c,^d,^⁎ , Chantal Jouanneau ^a, Stephan Rouzière ^d, Aurélien Bataille ^a, Alex Kellum ^c, Karine Provost ^e, Christian Mocuta ^f, Solenn Reguer ^f, Dominique Thiaudière ^f, Kris Jorissen ^g, John J. Rehr ^g, Alexandre Hertig ^a,^h, Éric Rondeau ^a,^h, Emmanuel Letavernier ^a,^b, Michel Daudon ^a,^b, Pierre Ronco ^a,^b
^a UMR S1155, INSERM/UPMC, 4, rue de la Chine, 75970 Paris cedex 20, France
^b AP-HP, Hôpital Tenon, Service d'Explorations Fonctionnelles, 4, rue de la Chine, 75970 Paris cedex 20, France
^c CNRS, LCMCP-UPMC, Collège de France, 11, place Marcelin-Berthelot, 75231 Paris cedex 05, France
^d Laboratoire de Physique des Solides, UMR 8502, CNRS, Bât. 510, Université Paris-11, 91405 Orsay, France
^e Institut de Chimie des Matériaux Paris Est, UMR 7182, CNRS, UPEC, 2–8, rue Henri-Dunant, 94320 Thiais, France
^f Synchrotron SOLEIL, L'Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette, France
^g Department of Physics, University of Washington, Seattle, Washington, 98195, USA
^h AP-HP, Hôpital Tenon, Service UNTR, 4, rue de la Chine, 75970 Paris cedex 20, France

^∗Corresponding author.

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Abstract

Nephrotoxicity is a specific and serious adverse effect of cisplatin which limits its utilization. Here we present an experimental approach to decipher its mechanisms focusing on the renal distribution of Pt and Zn in cisplatin exposed mice kidneys. We combined Synchrotron Radiation (S.R.) μX-ray fluorescence with statistical treatments. μX-ray fluorescence data were collected on a set of mice biopsies after cisplatin, oxaliplatin and carboplatin injections. Even if this investigation is based on a limited number of samples, these preliminary data seem to reveal a stronger correlation between the spatial repartition of Pt and Zn for cisplatin than for the other Pt containing drugs. The cisplatin injection induced a redistribution of medullary Zn across the corticomedullary junction where histological lesions develop. These results were confirmed by evaluation of Pearson's and Manders' co-localization coefficients. These data suggest that Zn is involved in the nephrotoxicity of cisplatin. This could lead to new diagnosis, physiopathological and even therapeutical approaches.

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Keywords : Cancer, Pt anticancer drugs, Nephrotoxicity