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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
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