Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

Hernández Esquivel L

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Título :	Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism
Creador:	Hernández Esquivel L
Nivel de acceso:	Open access
Palabras clave :	Adenosina Trifosfato - metabolismo - Ratas Antineoplásicos - toxicidad - Ratas biomarcadores - Ratas Presión Sanguínea - efectos de drogas - Ratas Cisplatino - toxicidad - Ratas Cobre - toxicidad - Ratas Interpretación Estadística de Datos - Ratas Doxorrubicina - toxicidad - - Ratas Metabolismo Energético - efectos de drogas - Ratas Cardiopatías - inducido químicamente - Ratas Cardiopatías - enzimología - Ratas Cardiopatías - patología - Ratas Técnicas In Vitro - métodos - Ratas Contracción Miocárdica - efectos de drogas - Ratas técnicas in vitro Masculino Contracción del miocardio - efectos de drogas - Ratas Miocardio - enzimología - Ratas Compuestos Organometálicos - toxicidad - Ratas Fosforilación Oxidativa- efectos de drogas - Ratas Consumo de Oxígeno - efectos de drogas - Ratas Adenosine Triphosphate - metabolism - Rats Antineoplastic Agents -toxicity - Rats Biomarkers - Rats Blood Pressure - drug effects - Rats Cisplatin - toxicity - Rats Copper - toxicity - Rats Data Interpretation, Statistical - Rats Doxorubicin - toxicity - Rats Energy Metabolism - drug effects - Rats Heart Diseases - chemically induced - Rats Heart Diseases- enzymology - Rats Heart Diseases- pathology - Rats Heart Function Tests - Rats Heart Rate - drug effects - Rats In Vitro Techniques - Rats Myocardial Contraction -drug effects - Rats Myocardium - enzymology - Rats Organometallic Compounds -toxicity - Rats Oxidative Phosphorylation - drug effects - Rats Oxygen Consumption - drug effects - Rats Cardiotoxicidad Rendimiento de trabajo Consumo de oxigeno 2-oxoglutarato deshidrogenasa piruvato deshidrogenasa Creatina quinasa Ratas Cardiotoxicity Work performance Oxygen consumption 2-oxoglutarate dehydrogenase Pyruvate dehydrogenase Creatine kinase - Rats
Descripción :	Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O2 consumption with half-maximal inhibitory concentrations (IC50) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC50 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin.
Colaborador(es) u otros Autores:	Marin-Hernandez A Pavon N Carvajal K Moreno-Sanchez R
Fecha de publicación :	2006
Tipo de publicación:	Artículo
Formato:	PDF
Fuente:	Toxicological and Applied Pharmacology 212(1):79-88
URI :	http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2139
Idioma:	eng
Aparece en las colecciones:	Artículos

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