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Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats

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Rocha Catalao, Carlos Henrique ; Souza, Anderson de Oliveira ; Santos-Junior, Nilton Nascimento ; Angenendt da Costa, Luis Henrique ; dos Santos, Jonathas Rodrigo ; Alberici, Luciane Carla ; Alves Rocha, Maria Jose
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: Molecular and Cellular Biochemistry; v. N/A, p. 11-pg., 2022-05-23.

Sepsis causes overproduction of inflammatory cytokines, organ dysfunction, and cognitive impairment in survivors. In addition to inflammation, metabolic changes occur according to the stage and severity of the disease. Understanding the role and place of metabolic disturbances in the pathophysiology of sepsis is essential to evaluate the framework of septic patients, predict the syndrome progress, and define the treatment strategies. We investigated the effect of simvastatin on the disease time course and on metabolic alterations, especially with respect to their possible consequences in the CNS of surviving rats. The animals of this study were weighed daily and followed for 10 days to determine the survival rate. In the first experiment, control or cecal ligation and puncture (CLP)-animals were randomized in 24 h, 48 h, and 10 days after septic induction, for bacterial load determination and quantification of cytokines. In the second experiment, control or CLP-animals were treated or not with simvastatin and randomized in the same three time points for cytokines quantification and assessment of their body metabolism and locomotor activity (at 48 h and 10 days), as well as the evaluation of cytoarchitecture and astrogliosis (at 10 days). The CLP-rats treated with simvastatin showed a reduction in plasma cytokines and improvement in metabolic parameters and locomotor activity, followed by minor alterations compatible with apoptosis and astrogliosis in the hippocampus and prefrontal cortex. These results suggest that the anti-inflammatory effect of simvastatin plays a crucial role in restoring energy production, maintaining a hypermetabolic state necessary for the recovery and survival of these CLP-rats. (AU)

Processo FAPESP: 17/12462-0 - Estudo do efeito neuroprotetor da sinvastatina nas disfunções cognitivas em animais sobreviventes à sepse
Beneficiário:Carlos Henrique Rocha Catalão
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado