On the toxicity and transport mechanisms of cisplatin in kidney tissues in comparison to a gold-based cytotoxic agent

Metallomics : Integrated Biometal Science
Sarah SpreckelmeyerAngela Casini

Abstract

Mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. Here, we studied the toxic effects and accumulation mechanisms of cisplatin in healthy rat kidneys ex vivo, using the Precision Cut Tissue Slices (PCTS) method. In addition, for the first time, we investigated the nephrotoxic effects of an experimental anticancer cyclometallated complex [Au(pyb-H)(PTA)Cl]PF6 (PTA = 1,3,5-triazaphosphaadamantane). The viability of the kidney slices after metallodrug treatment was evaluated by ATP content determination and histomorphology analysis. A concentration dependent decrease in viability of PCKS was observed after exposure to cisplatin or the Au(iii) complex, which correlated with the increase in slice content of Pt and Au, respectively. Metal accumulation in kidney slices was analysed by ICP-MS. The involvement of OCTs and MATE transporters in the accumulation of both metal compounds in kidneys was evaluated co-incubating the tissues with cimitedine, inhibitor of OCT and MATE. Studies of mRNA expression of the markers KIM-1, villin, p53 and Bax showed that cisplatin damages proximal tubules, whereas the Au(iii) complex preferentially affects the d...Continue Reading

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Citations

Mar 27, 2018·Chemistry : a European Journal·Benoît BertrandManfred Bochmann
Sep 12, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Morwen R M WilliamsManfred Bochmann
Jun 20, 2020·Drug Metabolism Reviews·Lianne J StevensEvita van de Steeg
Oct 17, 2019·Nanomaterials·Jacinta Oliveira PinhoMaria Manuela Gaspar

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Methods Mentioned

BETA
Biopsy
Assay
Protein Assay
PCR

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