A Complex Methodological Approach for the Screening of Efficient and Safe Cobalt Chelators

Abstract

Background:: Cobalt is an essential trace element, but it can also rarely cause cobalt toxicity due to its release from cobalt-containing medical devices. Currently, there are no approved selective cobalt chelators, which would represent an optimal treatment modality. Objective:: This study aimed to develop a simple and complex methodological approach for screening potential cobalt chelators and evaluating their potential toxicity. Methods:: Firstly, a simple spectrophotometric assay employing 1-nitroso-2-naphthol-3,6- disulfonic acid disodium salt (NNDSA) for screening cobalt chelation was standardized at a pathophysiologically relevant range of pH 4.5-7.5. Then, the suitability of the method was verified using four known metal chelators (EDTA, 8-hydroxyquinoline, chloroxine and nitroxoline). As cobalt can catalyse the Fenton reaction, the potential toxicity of cobalt-chelator complexes was also determined by employing a novel HPLC method with coulometric detection. The effect on erythrocyte haemolysis was tested as well. Results:: The NNDSA method had high sensitivity enabling the detection of 25-200 nM of cobalt ions depending on pH conditions. Measurements could be carried out in a wide range of wavelengths from 470 to 540 nm. All tested complexes of the selected chelators decreased the rate of the Fenton reaction. Interestingly, chloroxine mixed with cobalt ions caused marked lysis of erythrocytes in contrast to the other compounds. Conclusion:: The described complex methodological approach could serve as a simple yet precise tool for evaluating novel, effective and safe cobalt chelators.