Interactions of Platinum-Based Cytostatics with Metallothionein Revealed by Electrochemistry

Platinum-based cytostatics play an important role in the chemotherapy of various tumour diseases. Therefore, it is not surprising that there is a great effort for studying of the cytostatics and their fate in an organism. In this study, we aimed our attention at determination of cisplatin, carboplatin and oxaliplatin using stationary and flow electrochemical methods. Primarily, determination of the platinum based cytostatics using differential pulse voltammetry at hanging mercury drop electrode was optimized. Under the optimal conditions (supporting electrolyte: 2 ml of 0.36 M sulphuric acid containing 0.24 ml of hydrazine (10 mM) and 0.01 ml of formaldehyde (37 % aqueous solution, v/v), pH of the supporting electrolyte: 1.8, potential of accumulation: -0.7 V, time of accumulation: 120 s), limits of detection were estimated (3 S/N) down to tens of pg per ml for the studied drugs. Further, we investigated the interactions of the characterized drugs with peptide fragments of protein metallothionein, because the overexpression of metallothionein in tumour cells belongs to the one of the generally accepted mechanisms of resistance to these cytostatics. For this purpose, flow injection analysis with electrochemical detection was utilized. As it is well evident from the obtained experimental data, interactions between peptide fragments and platinum-based complexes proceeded differently, where oxaliplatin demonstrated the highest ability to form complex.