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

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.