Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide-induced hypocampal neuroinflammation in rats

J Cell Biochem. 2019 Mar;120(3):4081-4091. doi: 10.1002/jcb.27693. Epub 2018 Sep 27.

Abstract

Our study aimed to analyze the effect of ouabain (OUA) administration on lipopolysaccharide (LPS)-induced changes in hippocampus of rats. Oxidative parameters were analyzed in Wistar rats after intraperitoneal injection of OUA (1.8 µg/kg), LPS (200 µg/kg), or OUA plus LPS or saline. To reach our goal, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), in addition to levels of reduced glutathione (GSH), protein carbonyl (PCO) and lipid peroxidation (LPO) were evaluated. We also analyzed the membrane lipid profile and some important lipids for the nervous system, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidic acid and sphingomyelin. The group that received only LPS showed increased oxidative stress, as evidenced by an increase in LPO (about twice), PCO (about three times) levels, and CAT activity (80%). Conversely, administration of LPS decreased GSH levels (55%), and GPx activity (30%), besides a reduction in the amount of PI (60%) and PC (45%). By other side, OUA alone increased the amount of PI (45%), PE (85%), and PC (70%). All harmful effects recorded were attenuated by OUA, suggesting a protective effect against LPS-induced oxidative stress. The relevance of our results extends beyond changes in oxidative parameters induced by LPS, because nanomolar doses of OUA may be useful in neurodegenerative models. Other studies on other cardenolides and substances related issues, as well as the development of new molecules derived from OUA, could also be useful in general oxidative and/or cellular stress, a condition favoring the appearance of neuronal pathologies.

Keywords: hippocampus; lipopolysaccharide; membrane lipids; ouabain; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalase / metabolism
  • Disease Models, Animal
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Lipid Peroxidation / drug effects
  • Lipopolysaccharides / toxicity
  • Membrane Lipids / metabolism
  • Nervous System / drug effects
  • Nervous System / metabolism
  • Ouabain / pharmacology*
  • Oxidative Stress / drug effects*
  • Protein Carbonylation / genetics
  • Rats
  • Superoxide Dismutase / metabolism

Substances

  • Lipopolysaccharides
  • Membrane Lipids
  • Ouabain
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione