Cardiotoxic effects of chemotherapeutic agents with special emphasis on cisplatin
Cisplatin (CPT) is a long-standing widely used chemotherapeutic alkylating agent. Its main mechanism of action is by damaging the DNA, causing strand breaks which inhibit cell proliferation. In addition, they also alter ion channel function, intracellular calcium, and free radical production. Althou...
Guardado en:
| Autores principales: | , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2023
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/163681 |
| Aporte de: |
| Sumario: | Cisplatin (CPT) is a long-standing widely used chemotherapeutic alkylating agent. Its main mechanism of action is by damaging the DNA, causing strand breaks which inhibit cell proliferation. In addition, they also alter ion channel function, intracellular calcium, and free radical production. Although these additional mechanisms of action may contribute to their chemotherapeutic action, they frequently cause adverse reactions, and originate mechanisms of drug resistance. In this review, we focus on the properties of the adverse effects of CPT on the heart. In isolated hearts a biphasic effect of CPT on inotropism can be described, which is positive at concentrations below 5 μM and negative at higher concentrations. These effects could be explained by the ability of CPT to promote changes in Cav1.2 channels and intracellular Ca2+ in isolated cardiomyocytes. The biphasic inotropic behavior of the heart to CPT has good correlation with its actions on Cav1.2 currents and intracellular Ca2+.These findings suggest that CPT has several sites of impact on the heart, and that Cav1.2 channels and intracellular Ca2+ dysfunction are key players in the heart’s adverse reactions to CPT. |
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