Nuevas estrategias de espectrometría de masas para la obtención y cuantificación de bioimágenes de platino y determinación de proteínas ligadas a fármacos platinados en estudios de nefrotoxicidad

Abstract

Since the anticancer activity of cisplatin was discovered by chance in the 1970s, it has been successfully used in the treatment of numerous tumors, and is nowadays the most widely used drug in chemotherapy. However, several problems arise in its application, such as the appearance of intrinsic or developed resistance to the drug, as well as the appearance of different side effects. Among the latter, nephrotoxicity induced in cisplatin treatment, which limits the administrable dose of the drug, is highlighted. Therefore, other drugs with second and third generation Pt base have been developed in order to improve their properties. However, cisplatin is currently unavoidable in anticancer therapies. It is well known that the antineoplasic activity of cisplatin is due to its interaction with its main pharmacological target, DNA, which is coordinated by forming different cisplatin-DNA adducts that cause disruption in the double helix and thus causing cell death by apoptosis. However, due to the high reactivity of cisplatin, it can bind to other biomolecules different than its pharmacological target such as proteins. This interaction is of great importance as it plays a key role in its complicated mechanism of toxicity and in the appearance of drug resistance and side effects. Therefore, the study of these interactions is of great interest, as it may shed some light on the understanding of the mechanisms of nephrotoxicity, which would help in the design of improved therapies and nephroprotective drugs...