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Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-β did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase activity in mitochondrial-rich fraction in the group induced by amyloid-β, but for the cytosolic fraction, it has raised in the activity of pyruvate kinase activity in cerebral cortex. Further, meloxicam-loaded nanocapsules administration reduced adenylate kinase activity in the hippocampus of mice injected by amyloid-β. In conclusion we observed absence in short-term effects in kinases activities of energy metabolism in mice hippocampus and cerebral cortex using amyloid-β peptide model. These findings established the foundation to further study the kinases in phosphoryltransfer network changes observed in the brains of patients post-mortem with Alzheimer's disease. RESUMO Considerando que a doença de Alzheimer é uma doença neurodegenerativa prevalente em todo o mundo, buscou-se investigar o envolvimento da atividade de três quinases: creatinaquinase, piruvatoquinase e adenilatoquinase no hipocampo e no córtex cerebral em um modelo da doença de Alzheimer. Os camundongos Swiss, machos, adultos, receberam β-amiloide ou solução salina. Um dia depois, os camundongos foram tratados com nanocápsulas vazias (17 ml/kg) ou nanocápsulas contendo meloxicam (5 mg/kg) ou meloxicam livre (5 mg/kg). Os tratamentos foram realizados em dias alternados, até o final do ptotocolo experimental. No décimo quarto dia, as atividades das quinases foram avaliadas. A β-amiloide não alterou a atividade das quinases no hipocampo e no córtex cerebral dos camundongos. No entanto, o meloxicam livre diminuiu a atividade da creatinaquinase na fração mitocondrial no grupo induzido pela β-amiloide, mas na fração citosólica observou-se um aumento na atividade da piruvatoquinase no córtex cerebral. Além disso, o tratamento com as nanocápsulas contendo meloxicam diminuiu a atividade da adenilatoquinase no hipocampo dos camundongos induzidos pela β-amiloide. Em conclusão, observamos ausência de efeitos de curto prazo nas atividades das quinases do metabolismo energético no hipocampo e no córtex cerebral de camundongos, no modelo induzido com o peptídeo amiloide-β. Esses resultados estabeleceram uma base para um estudo mais aprofundado das quinases em alterações na rede de fosforiltransferência observadas nos cérebros de pacientes pós-morte com a doença de Alzheimer.

The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice. In liver, at 100 µM, compound a reduced the lipid peroxidation to the control levels, while compounds c and d partially reduced it. In brain, only compound d partially reduced the lipid peroxidation at 50 and 100 µM. Compound b did not have an effect on the lipid peroxidation. Thiol peroxidase-like and free radical scavenging activities are not involved in the antioxidant mechanisms of these compounds. Compounds did not present thiol oxidase-like activity and effect on the δ-aminolevulinate dehydratase. In vivo experiments showed that compound a caused an inhibition of licking time in the first and second phases, and edema formation induced by formalin. In conclusion, quinoline derivative without selenium presented better in vitro antioxidant effect and in vivo antinociceptive activity.