Immunomodulatory activity of ouabain in Leishmania leishmania amazonensis-infected Swiss mice

Jacob, P. L.; Leite, Jacqueline Alves; Alves, Anne; Rodrigues, Yara Katia; Amorim, Francianne M.; Néris, Patrícia L.N.; Oliveira, Márcia Rosa de; Rodrigues‐Mascarenhas, Sandra

doi:10.1007/s00436-012-3146-9

Cited by 34 publications

(38 citation statements)

References 38 publications

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“…In all in vivo experiments, 0.56 mg/kg ouabain (Sigma Aldrich) [ 14 , 17 , 18 ] or phosphate buffered saline (PBS) was given intraperitoneally (i.p.) for three consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, ouabain was shown to modulate function and cytokine production of monocytes in vitro [ 15 ] and dendritic cells [ 16 ]. Ouabain negatively modulated acute peritoneal inflammatory response induced by Leishmania amazonensis infection in Swiss mice [ 17 ]. It was also reported that ouabain presented anti-inflammatory and antinociceptive effects [ 18 ], but the mechanisms involved were still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Leite

Alves

Galvão

et al. 2015

Mediators of Inflammation

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Ouabain, a potent inhibitor of the Na+, K+-ATPase, was identified as an endogenous substance. Recently, ouabain was shown to affect various immunological processes. We have previously demonstrated the ability of ouabain to modulate inflammation, but little is known about the mechanisms involved. Thus, the aim of the present work is to evaluate the immune modulatory role of ouabain on zymosan-induced peritonitis in mice. Our results show that ouabain decreased plasma exudation (33%). After induction of inflammation, OUA treatment led to a 46% reduction in the total number of cells, as a reflex of a decrease of polymorphonuclear leukocytes, which does not appear to be due to cell death. Furthermore, OUA decreased TNF-α (57%) and IL-1β (58%) levels, without interfering with IL-6 and IL-10. Also, in vitro experiments show that ouabain did not affect endocytic capacity. Moreover, electrophoretic mobility shift assay (EMSA) shows that zymosan treatment increased (85%) NF-κB binding activity and that ouabain reduced (30%) NF-κB binding activity induced by zymosan. Therefore, our data suggest that ouabain modulated acute inflammatory response, reducing the number of cells and cytokines levels in the peritoneal cavity, as well as NFκB activation, suggesting a new mode of action of this substance.

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“…In all in vivo experiments, 0.56 mg/kg ouabain (Sigma Aldrich) [ 14 , 17 , 18 ] or phosphate buffered saline (PBS) was given intraperitoneally (i.p.) for three consecutive days.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Leite

Alves

Galvão

et al. 2015

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…Interestingly, these mice showed a decreased recruitment of granulocytes and macrophages into the lung tissue, whereas, at least in vitro, digoxin did not affect the bacteria-killing action of alveolar macrophages. Jacob et al [35] investigated the action of ouabain in murine leishmaniosis. The CG effectively prevented the infiltration of the peritoneal cavity with neutrophils and reduced the levels of TNFα and interferon γ (IFNγ) in the peritoneal exudate.…”

Section: Cftrmentioning

confidence: 99%

New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides

2017

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In the 19th century, cardio-active steroid glycosides, shortly cardiac glycosides, were scientifically established as drugs against heart failure. Their in vivo, cellular, and molecular actions as well as their predominant target, Na+-K+-ATPase, have been comprehensively investigated in the 20th century and the discovery of endogenous cardiac glycosides has fostered this research field. In the last years, however, results from clinical trials and meta-analyses have questioned their therapeutic value due to efficacy and safety issues. This has led to a considerable decline of their usage. Beyond the cardiovascular system, cardiac glycosides have been increasingly recognized as antitumor compounds and Na+-K+-ATPase has evolved into a promising drug target in oncology. A wealth of review articles exists that intensively discuss these topics. Surprisingly, the anti-inflammatory actions of cardiac glycosides, which were discovered in the 1960s, have so far hardly been perceived and have not yet been summarized. This review provides an overview of the in vivo and in vitro actions of cardiac glycosides on inflammatory processes and of the signaling mechanisms responsible for these effects: cardiac glycosides have been found to decrease inflammatory symptoms in different animal models of acute and chronic inflammation. Regarding the underlying mechanisms most research has focused on leukocytes. In these cells, cardiac glycosides primarily inhibit cell proliferation and the secretion of proinflammatory cytokines.

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“…expression of activation markers, endocytosis and cytokine secretion by human monocytes (Teixeira and Rumjanek, 2014). It was also described that ouabain has potential anti-inflammatory, analgesic (Vasconcelos et al, 2011) and anti-leishmanicidal properties in vivo (Jacob et al, 2013). Another role of ouabain in the immune system is related to the action of this hormone together with glucocorticoids on lymphocyte population.…”

Section: Introductionmentioning

confidence: 96%