RESUMO
BACKGROUND AND PURPOSE: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg(-1) body weight). EXPERIMENTAL APPROACH: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. KEY RESULTS: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. CONCLUSIONS AND IMPLICATIONS: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.
Assuntos
Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Apoptose/imunologia , Caspase 3/biossíntese , Caspase 3/efeitos dos fármacos , Caspase 3/imunologia , Cisplatino/administração & dosagem , Cóclea/imunologia , Cóclea/patologia , Eletrofisiologia , Ativação Enzimática/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Injeções Intraperitoneais , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/imunologiaRESUMO
Nasopharyngeal carcinoma is frequently diagnosed in advanced stages due to the anatomic characteristics of its site of origin and of the inspecificity of many of its clinical manifestations. However, cure rates are directly related with the early diagnosis. In this study of 200 patients affected by this tumor we analyse the different clinical manifestations, their chronology and their value as early indicators of nasopharyngeal tumour.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Nasofaríngeas/patologia , Carcinoma de Células Escamosas/complicações , Diagnóstico Diferencial , Humanos , Neoplasias Nasofaríngeas/complicações , Otite Média com Derrame/diagnóstico , Otite Média com Derrame/etiologia , Recidiva , Estudos RetrospectivosRESUMO
Los carcinomas nasofaríngeos son diagnosticados frecuentemente en estadios avanzados, debido a las características anatómicas de su ligar de origen y a la inespecifidad de muchas de sus manifestaciones clínicas. Sin embargo, los índices de curación están relacionados directamente con la precocidad del diagnóstico. En el presente estudio de 200 pacientes afectados con este tumor se hace un análisis de las distintas manifestaciones clínicas, de su cronología y de su valor como indicadores precoces de tumor nasofaríngeo (AU)
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