RESUMO
Apoptosis plays a central role not only in the physiological processes of kidney growth and remodeling, but also in various human renal diseases and drug-induced nephrotoxicity. We present in a synthetic fashion the main molecular and cellular pathways leading to drug-induced apoptosis in kidney and the mechanisms regulating it. We illustrate them using three main nephrotoxic drugs (cisplatin, gentamicin, and cyclosporine A). We discuss the main regulators and effectors that have emerged as key targets for the design of therapeutic strategies. Novel approaches using gene therapy, antisense strategies, recombinant proteins, or compounds obtained from both classical organic and combinatorial chemistry are examined. Finally, key issues that need to be addressed for the success of apoptosis-based therapies are underlined.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Cisplatino/toxicidade , Ciclosporina/toxicidade , Gentamicinas/toxicidade , Rim/efeitos dos fármacos , Animais , Cisplatino/metabolismo , Ciclosporina/metabolismo , Gentamicinas/metabolismo , Humanos , Rim/citologia , Redes e Vias Metabólicas , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Insuficiência Renal/metabolismoRESUMO
The stability and compatibility of ceftazidime have been examined in the context of its potential use in concentrated solutions for continuous infusion in patients suffering from severe nosocomial pneumonia and receiving other intravenous medications by the same route. Ceftazidime stability in 4 to 12% solutions was found satisfactory (<10% degradation) for 24 h if kept at a temperature of 25 degrees C (77 degrees F) maximum. Studies mimicking the simultaneous administration of ceftazidime and other drugs as done in clinics showed physical incompatibilities with vancomycin, nicardipine, midazolam, and propofol and a chemical incompatibility with N-acetylcystein. Concentrated solutions (50 mg/ml) of erythromycin or clarithromycin caused the appearance of a precipitate, whereas gentamicin, tobramycin, amikacin, isepamicin, fluconazole, ketamine, sufentanil, valproic acid, furosemide, uradipil, and a standard amino acid solution were physically and chemically compatible.