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

Garcia, Israel José Pereira; Kinoshita, Paula Fernanda; Silva, Lílian Nara David e; Busch, Mileane De Souza; Atella, Geórgia C.; Scavone, Cristóforo; Cortes, Vanessa Faria; Barbosa, Leandro A.; Santos, Hérica de Lima

doi:10.1002/jcb.27693

Cited by 24 publications

(30 citation statements)

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“…To enhance the concentration of circulating ouabain, intraperitoneal injections of ouabain at doses of 1-1.8 µg/kg are widely used [34,39,40]. In this study, rats were treated with ouabain at dose of 1 µg/kg for four days and this experimental protocol was shown doubled serum ouabain level from baseline 0.89 nM to 1.69 nM [34].…”

Section: Discussionmentioning

confidence: 96%

“…Hindlimb unloading is known to increase oxidative stress [66,67], which may affect the activity of Na,K-ATPase in various cellular systems [68,69], including skeletal muscle [70]. Intraperitoneal injection of ouabain (1.8 µg/kg) is known to attenuate oxidative stress in lipopolysaccharide-induced neuroinflammation in rats [39]. Moreover, ouabain is suggested to play an important role in the control of NF-κB activation [71], where the α2 Na,K-ATPase/NF-κB pathway contributes to neuroinflammatory processes [72].…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence indicates a broad therapeutic potential of circulating cardiotonic steroids, including ouabain [9,36,[38][39][40][41]. The knowledge of molecular mechanisms behind the regulatory effects of circulating ouabain in skeletal muscle and their functional significance for muscle pathology could be useful for development of a new effective therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

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Vilchinskaya

et al. 2021

IJMS

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Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is characteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its disuse-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with ouabain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were studied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemistry were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depolarization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate acetyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of interleikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

Кравцова

Paramonova

Vilchinskaya

et al. 2021

IJMS

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“…In vivo studies were performed using isolated hippocampus due to its high sensitivity to oxidative stress. Neural tissue has a high rate of oxygen consumption and possesses a high metabolic activity, and therefore, is a tissue more vulnerable to lipid peroxidation as compared to other tissues 32 . Consequently, antioxidant peptides, which rapidly exert their biological functions, have a potential to prevent neuronal damage related to lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons

Sousa

Oliveira

et al. 2020

Sci Rep

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cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. the peptides obtained possessed the amino acid sequences, GVVDiLKGAAKDLAGH and GVVDiLKGAAKDLAGHLASKV, with monoisotopic masses of [M + H] ± = 1563.8 Da and [M + H] ± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and nf-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. these functional properties suggest possible to neuromodulatory therapeutic applications.The skin of amphibians has been the subject of interest and study of several research groups as well as pharmaceutical industries, due to the abundance and diversity of bioactive molecules with potential biotechnological applications, especially for the production of new drugs 1 . The characteristic way of living of amphibians is divided between aquatic and the terrestrial environment 2 . They possess a highly sensitive skin that is essential to its respiration and is highly vulnerable to environmental aggressions, such as desiccation, attack of microorganisms, ultraviolet radiation, and injuries 3 . This vulnerability has culminated in the development of an innate defense system as a survival strategy based on the expression, production, accumulation, and secretion of bioactive www.nature.com/scientificreports www.nature.com/scientificreports/ against E. coli with MIC of 125 μg/mL (Fig. 4) and inhibition percentage corresponding to 34.17 ± 11.66%. The optical density (630 nm) of E. coli decreased in a dose-dependent manner, showing significant reduction on viability for both the ocellatins at concentrations between 125 and 1000 μg/mL. The value 125 μg/mL of MIC is too high to be characterized as having significant antibacterial potential. Moreover, only Ocellatin-K1(1-16) showed any significant activity against S. aureus featuring MICs of 31.25 μg/mL and inhibition percentage corresponding to 30.79 ± 10.27%. This activity was not seen to be conc...

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“…LPS is widely used to induce neuroin ammation [2,3,49,54,62]. Numerous studies showed that LPS treatment could induce central in ammatory response associated with proin ammatory cytokines production, glial cell activation, as well as ROS and RNS generation [2,5,7,40,44,47,54,[63][64][65][66][67][68][69].…”

Section: Discussionmentioning

confidence: 99%

Ibrutinib alleviated LPS-induced neuroinflammation and synaptic defects in a mouse model of depression

Ali

et al. 2020

Preprint

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Background Previous studies indicate a close association between the altered immune system and major depressive disorders. and inhibition of neuroinflammation may represent an alternative mechanism to treat depression. Recently, the anti-inflammatory activity of ibrutinib has been reported, however, the effect of ibrutinib on neuroinflammation allied depression and its underlying mechanism has not been comprehensively studied. Therefore, we aimed to elucidate the potential anti-depressive role and mechanism of ibrutinib against neuroinflammation induced depression as well as synaptic defects. Methods Adult C57BL/6J male mice weighing 25–30 g (age 7–8 weeks) were treated with LPS (2 mg/kg BW i.p) and 50 mg/kg BW ibrutinib, orally. Depressive-like behaviors were assessed by FST and SPT, cytokine levels were determined by ELISA, ROS, TBARs, and Nitric oxides were measured via biochemical assays, Iba-1 and GFAP expression were determined by immunofluorescence. Further, spine density was measured by Golgi staining, while NF-kB, Nrf2, SOD2, HO-1, NLRP3, P38, Caspase-1, BDNF, PSD95, and synaptophysin were measured by immunoblotting. Results Our results showed that ibrutinib treatment significantly reduced LPS induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing pro-inflammatory cytokines level, normalizing redox signaling and it’s a downstream component including Nrf2, HO-1, and SOD2 as well as glial cells activation markers such as Iba-1 and GFAP expression. Further, ibrutinib treatment inhibited LPS activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling. Interestingly, LPS reduced dendritic spines numbers, expression of BDNF and synaptic related markers including PSD95, snap25, and synaptophysin were improved by ibrutinib treatment in the hippocampal area of the mice brain. Conclusion In conclusion, our finding suggested that ibrutinib could alleviate neuroinflammation and synaptic defects, rendering its antidepressant potential against LPS induced neuroinflammation and depression.

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

Cited by 24 publications

References 49 publications

Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons

Ibrutinib alleviated LPS-induced neuroinflammation and synaptic defects in a mouse model of depression

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