RESUMO
Fluoxetine shows controversial lung effects as it prevents pulmonary hypertension in adult rats but exposure during gestation causes pulmonary hypertension in neonatal rats. In the present study, we tested the null hypothesis that the antidepressant drug fluoxetine does not modify the development of bronchopulmonary dysplasia (BPD) in neonatal rats. Experimental categories included I: room air (controls) with daily injection of saline; II: room air with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks; III: 60% oxygen with daily injection of saline; and IV: 60% oxygen with daily injection of 10 mg/kg fluoxetine, i.p., during two weeks. Hyperoxia resulted in significant reduction in alveolar density and an increase in pulmonary endocrine cells, as well as increases in muscle layer areas of bronchi and arteries. Fluoxetine treatment generated a further increase in muscularisation and did not significantly modify the hyperoxia-induced reductions in alveolar density and increases in the endocrine cells. In hyperoxia, Real-Time PCR showed a lower pulmonary expression of vascular endothelial growth factor (VEGF) with no significant changes in the expression of matrix metalloproteinases (MMP) 2 and 12. Fluoxetine did not affect VEGF or MMP-2 expression but it significantly increased MMP-12 mRNA in both normoxic and hyperoxic groups. Zymographic analysis of MMP-2 activity in bronchoalveolar fluid showed a significantly reduced MMP-2 activity in hyperoxia, while fluoxetine treatment restored MMP-2 activity to levels comparable with the normoxic group. In conclusion, our data show that fluoxetine may worsen bronchial and arterial muscularisation during development of BPD and may up-regulate MMP expression or activity.
Assuntos
Antidepressivos de Segunda Geração/toxicidade , Fluoxetina/toxicidade , Hiperóxia/complicações , Lesão Pulmonar/etiologia , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Animais , Animais Recém-Nascidos , Sequência de Bases , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Modelos Animais de Doenças , Feminino , Humanos , Hiperóxia/genética , Hiperóxia/metabolismo , Recém-Nascido , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Células Neuroendócrinas/efeitos dos fármacos , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/patologia , Ubiquitina Tiolesterase/metabolismo , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
In order to evaluate the possible effects of diagnostically employed ultrasounds on DNA turnover, 35 Wistar strain rats were subjected to an ultrasonic frequency band of 2.25 MHz for exposure times varying from 10 to 500 seconds. Upon administration of thymidine tritiate, it was observed that capacity to absorb the substance remained largely normal in those rats exposed for up to 40 seconds, but was diminished where longer exposure times were employed.
