Ouabain attenuates ovalbumin-induced airway inflammation

Galvão, José Guilherme Ferreira Marques; Cavalcante‐Silva, Luiz Henrique Agra; Carvalho, Deyse Cristina Madruga; Ferreira, Laércia Karla Diega Paiva; Monteiro, Talissa Mozzini; Alves, Adriano Francisco; Ferreira, Larissa Adilis Maria Paiva; Gadelha, Francisco Allysson Assis Ferreira; Piuvezam, Márcia Regina; Rodrigues‐Mascarenhas, Sandra

doi:10.1007/s00011-017-1092-9

Cited by 24 publications

(19 citation statements)

References 74 publications

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“…It is noteworthy that in this study the authors used high doses of ouabain both in vitro and in vivo . This contrasts with other studies that show a reduction of a different pattern of cytokines, including IL-1β (Leite et al, 2015 ) with lower ouabain doses in presence of inflammatory stimulus (Jacob et al, 2013 ; Galvão et al, 2017 ).…”

Section: Ouabain As a Modulator Of Inflammationcontrasting

confidence: 75%

“…This ouabain effect was also demonstrated in peritoneal inflammation induced by mitogen concanavalin A (de Vasconcelos et al, 2011 ). Furthermore, in airway allergic inflammation model, ouabain has an anti-migratory effect (Galvão et al, 2017 ). Ray and Samanta ( 1997 ) have also demonstrated that ouabain impairs in vitro human neutrophil migration, by interfering with IL-8 receptor recycling.…”

Section: Ouabain As a Modulator Of Inflammationmentioning

confidence: 99%

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Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

et al. 2017

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Since the discovery of ouabain as a cardiotonic steroid hormone present in higher mammals, research about it has progressed rapidly and several of its physiological and pharmacological effects have been described. Ouabain can behave as a stress hormone and adrenal cortex is its main source. Direct effects of ouabain are originated due to the binding to its receptor, the Na+/K+-ATPase, on target cells. This interaction can promote Na+ transport blockade or even activation of signaling transduction pathways (e.g., EGFR/Src-Ras-ERK pathway activation), independent of ion transport. Besides the well-known effect of ouabain on the cardiovascular system and blood pressure control, compelling evidence indicates that ouabain regulates a number of immune functions. Inflammation is a tightly coordinated immunological function that is also affected by ouabain. Indeed, this hormone can modulate many inflammatory events such as cell migration, vascular permeability, and cytokine production. Moreover, ouabain also interferes on neuroinflammation. However, it is not clear how ouabain controls these events. In this brief review, we summarize the updates of ouabain effect on several aspects of peripheral and central inflammation, bringing new insights into ouabain functions on the immune system.

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Section: Ouabain As a Modulator Of Inflammationcontrasting

confidence: 75%

Section: Ouabain As a Modulator Of Inflammationmentioning

confidence: 99%

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

et al. 2017

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“…Related researches also proposed ouabain reduced the polymorphonuclear leukocytes in animal models of peritonitis induced by concanavalin A and Leishmania amazonensis [ 9 , 10 ]. Ouabain was also proven to alleviate allergic airway inflammation in a mouse model, which inhibits inflammatory cell migration into the lungs [ 11 ]. Leite and colleagues demonstrated that ouabain reduced neutrophil migration and decreased vascular permeability in peritonitis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent data demonstrated the anti-inflammatory and analgesic effects of ouabain by inhibiting NF-κB activation [ 9 , 10 ]. It has also been demonstrated that ouabain could negatively modulate airway inflammation in ovalbumin-induced asthma [ 11 ]. However, whether ouabain could regulate inflammatory responses in LPS-induced ALI in mice has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury

et al. 2018

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BackgroundOuabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited inflammatory reactions and regulated immunological processes. Our present study aimed to investigate the therapeutic role of ouabain on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Material/MethodsOuabain (0.1 mg/kg) or vehicles were intraperitoneally injected into male C57BL/6J mice once a day for 3 consecutive days. One hour after the last injection of ouabain, LPS (5 mg/kg) was administrated through intranasal instillation to induce ALI. 6 hours and 24 hours later, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested to detect the protective effects of ouabain, including protein concentration, inflammation cell counts, lung wet-to-dry ratio, and lung damage.ResultsThe results showed that ouabain attenuated LPS-induced ALI in mice, which was indicated by alleviated pathological changes, downregulated TNF-α, IL-1β, and IL-6 production, inhibited neutrophils infiltration and macrophages, and ameliorated pulmonary edema and permeability. Further results found the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in LPS-induced ALI.ConclusionsThese results suggest that ouabain negatively modulates the severity of LPS-induced ALI.

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“…Besides, this steroid inhibits proinflammatory cytokines, such as interleukin 1 β (IL-1 β ) and tumor necrosis factor α (TNF- α ), which could be associated with p38 mitogen-activated protein kinase (MAPK p38) and nuclear factor kappa B- (NF- κ B-) reduced activity [22, 23]. Recently, another study of our group has shown that ouabain negatively modulates pulmonary inflammation, reducing eosinophil migration, Th2 profile cytokines, and mucus production in bronchioles [24]. Furthermore, by similar mechanisms, other studies demonstrated the anti-inflammatory effects of digoxin and bufalin [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Marinobufagenin Inhibits Neutrophil Migration and Proinflammatory Cytokines

Carvalho

Cavalcante-Silva

Lima

et al. 2019

Journal of Immunology Research

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Cardiotonic steroids, such as ouabain and digoxin, are known to bind to Na+/K+-ATPase and to promote several biological activities, including anti-inflammatory activity. However, there are still no reports in the literature about inflammation and marinobufagenin, a cardiotonic steroid from the bufadienolide family endogenously found in mammals. Therefore, the aim of this work was to analyze, in vivo and in vitro, the role of marinobufagenin in acute inflammation. Swiss mice were treated with 0.56 mg/kg of marinobufagenin intraperitoneally (i.p.) and zymosan (2 mg/mL, i.p.) was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for counting cells by optical microscopy and proinflammatory cytokine quantification (IL-1β, IL-6, and TNF-α) by immunoenzymatic assay (ELISA). Zymosan stimulation, as expected, induced increased cell migration and proinflammatory cytokine levels in the peritoneum. Marinobufagenin treatment reduced polymorphonuclear cell migration and IL-1β and IL-6 levels in the peritoneal cavity, without interfering in TNF-α levels. In addition, the effect of marinobufagenin was evaluated using peritoneal macrophages stimulated by zymosan (0.2 mg/mL) in vitro. Marinobufagenin treatment at different concentrations (10, 100, 1000, and 10000 nM) showed no cytotoxic effect on peritoneal macrophages. Interestingly, the lowest concentration, which did not inhibit Na+/K+-ATPase activity, attenuated proinflammatory cytokines IL-1β, IL-6, and TNF-α levels. To investigate the putative mechanism of action of marinobufagenin, the expression of surface molecules (TLR2 and CD69) and P-p38 MAPK were also evaluated, but no significant effect was observed. Thus, our results suggest that marinobufagenin has an anti-inflammatory role in vivo and in vitro and reveals a novel possible endogenous function of this steroid in mammals.

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Ouabain attenuates ovalbumin-induced airway inflammation

Abstract: Therefore, our data demonstrate that ouabain negatively modulates allergic airway inflammation induced by OVA.

Cited by 24 publications

References 74 publications

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury

Marinobufagenin Inhibits Neutrophil Migration and Proinflammatory Cytokines

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