Ouabain attenuates the oxidative stress induced by lipopolysaccharides in the cerebellum of rats

Abstract

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.

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

“…In our study LPS was able to induce a hypoccampal oxidative stress, demonstrated by the increase of lipid peroxidation and the decrease of GSH (Figure A and B, respectively). In agreements with previous studies showing that LPS caused an increase in lipid peroxidation and a decrease in GSH content in the hippocampus of Swiss mice, hippocampus of newborn rats and in cerebellum of rats . Moreover, Figure C corroborate data by Barreiro et al, who demonstrated increase of carbonylated protein in Sprague Dawley rats after LPS administration.…”

Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

“…2) Inhibiting Na pumps may accelerate the loss of ion gradients, thus enhancing edema formation. These contrasting CTS effects have been previously described in the CNS (34)(35)(36)(37) but are beyond the scope of the present study.…”

Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels

“…Notably, depletion of membrane cholesterol resulted in the displacement of claudin-3, -4, -7 and occludin from the cholesterol rich domains associated with TJs, while claudin-1 was unaffected [ 52 ]. Intriguingly, a neuroprotective effect of ouabain against LPS-induced oxidative stress in rat cerebellum involves promoting membrane lipid remodeling [ 53 ]. Further studies are necessary to testify features of the Na,K-ATPase/claudin-1 functional interaction and to identify their precise molecular basis.…”

“…It was shown in primary culture of rat cortical neurons that ouabain at sub-nanomolar concentrations can prevent Ca 2+ overload and neuronal apoptosis in excitotoxic stress [ 62 ]. The same doses of chronically administrated ouabain used in this study (1 µg/kg–1.8 µg/kg) significantly improves mouse recovery following traumatic brain injury [ 63 ] and attenuates the oxidative stress induced by LPS in rat cerebellum [ 53 ]. The role of ouabain in inflammatory processes in the central nervous system is reviewed elsewhere [ 64 ].…”