RESUMO
Multiple sclerosis (MS) is the most prevalent inflammatory demyelinating disease of the central nervous system. Besides other pathophysiological mechanisms, mitochondrial injury is crucially involved in the development and progression of this disease. Mitochondria have been identified as targets for the peptide hormone melatonin. In the present study, we sought to evaluate the impact of oxidative stress on mitochondrial density and enzyme transcription during experimentally induced demyelination and the protective influence of melatonin. Adult male mice were fed with cuprizone for 5 weeks which caused severe demyelination of the corpus callosum (CC). Animals were simultaneously treated with melatonin by daily intra-peritoneal injections. Melatonin exposure reversed cuprizone-induced demyelination and axon protection. Transmission electron microscopy demonstrated significantly increased mitochondrial numbers and slightly increased mitochondrial size within CC axons after cuprizone exposure. Melatonin antagonized these effects and, in addition, induced the expression of subunits of the respiratory chain complex over normal control values reflecting a mechanism to compensate cuprizone-mediated down-regulation of these genes. Similarly, melatonin modulated gene expression of mitochondrial fusion and fission proteins. Biochemical analysis showed that oxidative stress induced by cuprizone was regulated by melatonin. The data implicate that melatonin abolishes destructive cuprizone effects in the CC by decreasing oxidative stress, restoring mitochondrial respiratory enzyme activity and fusion and fission processes as well as decreasing intra-axonal mitochondria accumulation.
Assuntos
Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Animais , Cuprizona/toxicidade , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Inibidores da Monoaminoxidase/toxicidade , Esclerose Múltipla/induzido quimicamente , Proteína Proteolipídica de Mielina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/genética , Oxirredutases/metabolismoRESUMO
BACKGROUND: Since nitric oxide (NO) has an oxidant activity, lower levels following a varicocelectomy may result in better functioning sperm, improved semen quality and consequently higher fertility rates. However, this procedure should be examined in more detail. OBJECTIVES: Accordingly, this study was performed to compare the before and after varicocelectomy levels of NO in the seminal fluid of infertile men. PATIENTS AND METHODS: In this before and after comparative study, 20 consecutive patients attending a training hospital in Tehran, Iran were recruited. All of these men had primary or secondary infertility accompanied with a varicocele. A semen sample was collected from the men in two phases, first before their varicocelectomy and two months after their operation. RESULTS: NO levels differed significantly across the study and the mean (± standard deviation) levels of NO in the patients were 30.59 ± 10.35 µM/L and 21.48 ± 32.14 µM/L in the before and after phases of the study, respectively (P = 0.009). CONCLUSIONS: According to the results obtained in this study, it may be concluded that in future, levels of NO should be taken into consideration together with other parameters for the evaluation of patients who are affected by varicoceles, to determine probable therapeutic responses.