Ouabain attenuates the oxidative stress induced by lipopolysaccharides in the cerebellum of rats
Autor: | Gabriela Machado Parreira, Hérica de Lima Santos, Paula Fernanda Kinoshita, Cristoforo Scavone, Italo de Oliveira Braga, Julio A. Mignaco, Israel José Pereira Garcia, Leandro A. Barbosa |
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Rok vydání: | 2017 |
Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Pharmacology medicine.disease_cause Biochemistry Neuroprotection Ouabain RATOS Lipid peroxidation Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebellum Gangliosides medicine Animals Rats Wistar Na+/K+-ATPase Molecular Biology Phospholipids chemistry.chemical_classification Glutathione Peroxidase biology Superoxide Dismutase Chemistry Glutathione peroxidase Cell Biology Glutathione Catalase Rats Oxidative Stress Cholesterol 030104 developmental biology Gene Expression Regulation biology.protein Lipid Peroxidation Sodium-Potassium-Exchanging ATPase Injections Intraperitoneal 030217 neurology & neurosurgery Oxidative stress medicine.drug |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1097-4644 0730-2312 |
DOI: | 10.1002/jcb.26377 |
Popis: | Our study aimed to analyze the effect of ouabain administration on lipopolysaccharide (LPS)-induced changes in oxidative parameters, membrane lipid composition, and the activities of some important enzymes of the nervous system. The content of phospholipids, cholesterol, and gangliosides were analyzed in Wistar rats after intraperitoneal injection of ouabain (1.8 μg/kg), LPS (200 μg/kg), or saline. Oxidative parameters were also evaluated, including the activities of superoxide dismutase, catalase and glutathione peroxidase, the levels of glutathione and lipid peroxidation, as well as Na,K-ATPase activity and the level of glutamate transporter EAAT4. Administration of LPS resulted in increased oxidative stress, as evidenced by an increase in lipid peroxidation levels, glutathione peroxidase activity, decreased catalase activity and reduced glutathione levels. All changes recorded were attenuated by pretreatment with ouabain. Administration of ouabain plus LPS enhanced the total ganglioside content and EAAT4 levels, but failed to alter the Na,K-ATPase activity. Our data suggest a neuroprotective effect of ouabain against LPS-induced oxidative stress by promoting membrane lipid remodeling and increasing the expression of glutamate transporter EAAT4. Our results emphasize that the observed oxidative stress is not correlated with Na,K-ATPase, but with a possible ouabain-mediated effect on cellular signaling. The relevance of our results extends beyond LPS-induced changes in oxidative parameters, as nanomolar doses of ouabain might prove useful in neurodegenerative models. Further study of other cardenolides and related molecules, as well as the development of new molecules derived from ouabain, could also prove useful in the fight against the oxidative and/or general cell stress triggered by neuronal pathologies. |
Databáze: | OpenAIRE |
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