Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent

AVALIAÇÃO DO EFEITO DO EXTRATO HIDROALCOÓLICO DE Zollernia ilicifolia (FABACEAE) COMO GASTROPROTETOR EM RATOS

A Zollernia ilicifolia (Fabaceae) é uma planta nativa da Floresta Tropical Atlântica, e utilizada principalmente contra úlceras e problemas estomacais. O objetivo deste estudo foi avaliar o efeito gastroprotetor do extrato hidroalcoólico de Zollernia ilicifolia em ratos, através dos complexos da cadeia respiratória mitocondrial e da análise histológica do estômago dos ratos submetidos a um modelo animal de gastrite induzido por indometacina. Ratos Wistar adultos foram tratados com extrato e água destilada (controle), por meio de gavagem. Os animais foram submetidos a jejum por 24h; após esse período foi administrado indometacina em dois grupos e água destilada nos outros dois grupos. Os animais foram eutanasiados após 6 horas por decapitação para exerese do estômago e observação das lesões gástricas e posteriormente para avaliação da cadeia respiratória mitocondrial. Os resultados mostraram que o extrato não foi capaz de prevenir o aumento da lesão induzida pela indometacina e também pode ser observado que o extrato não pôde reverter à inibição da atividade da cadeia respiratória mitocondrial

AVALIAÇÃO DO EFEITO DO EXTRATO HIDROALCOÓLICO DE Zollernia ilicifolia (FABACEAE) COMO GASTROPROTETOR EM RATOS

A Zollernia ilicifolia (Fabaceae) é uma planta nativa da Floresta Tropical Atlântica, e utilizada principalmente contra úlceras e problemas estomacais. O objetivo deste estudo foi avaliar o efeito gastroprotetor do extrato hidroalcoólico de Zollernia ilicifolia em ratos, através dos complexos da cadeia respiratória mitocondrial e da análise histológica do estômago dos ratos submetidos a um modelo animal de gastrite induzido por indometacina. Ratos Wistar adultos foram tratados com extrato e água destilada (controle), por meio de gavagem. Os animais foram submetidos a jejum por 24h; após esse período foi administrado indometacina em dois grupos e água destilada nos outros dois grupos. Os animais foram eutanasiados após 6 horas por decapitação para exerese do estômago e observação das lesões gástricas e posteriormente para avaliação da cadeia respiratória mitocondrial. Os resultados mostraram que o extrato não foi capaz de prevenir o aumento da lesão induzida pela indometacina e também pode ser observado que o extrato não pôde reverter à inibição da atividade da cadeia respiratória mitocondrial

MITOCHONDRIAL RESPIRATORY CHAIN AND CREATINE KINASE ACTIVITIES IN mdx MOUSE BRAIN

In this study we investigated energy metabolism in the mdx mouse brain. To this end, prefrontal cortex, cerebellum, hippocampus, striatum, and cortex were analyzed. There was a decrease in Complex I but not in Complex 11 activity in all structures. There was an increase in Complex III activity in striatum and a decrease in Complex IV activity in prefrontal cortex and striatum. Mitochondrial creatine kinase activity was increased in hippocampus, prefrontal cortex, cortex, and striatum. Our results indicate that there is energy metabolism dysfunction in the mdx mouse brain. Muscle Nerve 41: 257-260, 2010CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC)FAPESCInstituto Cerebro e MenteInstituto Cerebro e MenteUnited Nations Educational, Scientific and Cultural Organization (UNESCO)UNES

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent

Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability