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Eur J Med Chem ; 44(4): 1554-69, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18782645

RESUMEN

This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03-0.1 LD(50)). A whole principle of this therapy is novel: (25)Mg(2+)-magnetic isotope effect selectively stimulates the ATP overproduction in the oxygen-depleted cells due to (25)Mg(2+) released by the nanoparticles. Being membranotropic cationites, these "smart nanoparticles" release the overactivating paramagnetic cations only in response to the metabolic acidic shift. The resulting positive changes in the heart cell energy metabolism may help to prevent and/or treat the local myocardial hypoxic disorders and, hence, protect the heart muscle from a serious damage in a vast variety of the hypoxia-caused clinical situations including both doxorubicin and 1-methylnicotineamide cardiotoxic side effects. Both pharmacokinetics and pharmacodynamics of the drug proposed make it suitable for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes.


Asunto(s)
Adenosina Trifosfato/biosíntesis , Fulerenos/farmacología , Magnesio/química , Magnetismo , Miocardio/metabolismo , Nanopartículas/química , Porfirinas/química , Animales , Descubrimiento de Drogas , Fulerenos/química , Fulerenos/metabolismo , Fulerenos/farmacocinética , Corazón/efectos de los fármacos , Concentración de Iones de Hidrógeno , Hipoxia/inducido químicamente , Hipoxia/metabolismo , Isótopos/química , Magnesio/metabolismo , Masculino , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Miocardio/ultraestructura , Difracción de Neutrones , Oxígeno/metabolismo , Ratas , Ratas Wistar , Dispersión del Ángulo Pequeño
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