DNA damage after intracerebroventricular injection of ouabain in rats

Jornada, Luciano K.; Valvassori, Samira S.; Arent, Camila O.; Leffa, Daniela Dimer; Damiani, Adriani A.; Hainzenreder, Giana; Ferreira, Camila L.; Moretti, Morgana; Andrade, Vanessa Moraes de; Quevedo, Joao L De

doi:10.1016/j.neulet.2009.12.072

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…Moreover, this effect can last for seven days after a single ICV infusion (Riegel et al, 2009). OUA treatment is associated with severe neuronal damage and high levels of oxidative stress through the increased formation of lipid and protein oxidation products along with decreased BDNF levels in the brain (Riegel et al, 2009, Jornada et al, 2010). Some of these changes were modified by lithium and valproate (Jornada et al, 2011).…”

Section: Pharmacological Models Of Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (~2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying ‘mood’ cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.

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Section: Pharmacological Models Of Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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“…Unlike tumor cells, normal proliferating cells have an intact DNA damage response that would allow them to repair the DNA damage and therefore to survive treatment with these DNA-damaging compounds [34][35][36]. Because previous reports showed that some cardiac glycosides induce DNA damage [11,[37][38][39], we tested whether NOE induced DNA damage and if such damage participated in the cytotoxicity of the extract. We initially tested the cytotoxicity of NOE in cells with and without BRCA2 (a tumor suppressor gene which plays a critical role in DNA damage repair via the HR repair pathway).…”

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confidence: 99%

A Hydroalcoholic Extract from the Leaves of Nerium oleander Inhibits Glycolysis and Induces Selective Killing of Lung Cancer Cells

et al. 2013

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Cardiac glycosides are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to inhibit the Na + /K +-ATPase pump. The lactone moiety at position 17 defines the two classes of cardiac glycoside: cardenolides (with the lactone 2-fu-ranone) and bufadienolides (with the lactone 2pyrone). Numerous cardiac glycosides (e.g., digitoxin, digoxin, ouabain, oleandrin, and proscillaridin) have been isolated from plants (e.g., Digitalis purpurea, Digitalis lannata, Strophantus gratus, Nerium oleander, and Urginea martima). Several cardiac glycosides have also been found in amphibians and mammals, including digoxin, oua

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“…As reported, ouabain might induce reversible peripheral and central early DNA damage. 29 Hence, the cell cycle arrested in G2/M induced by ouabain might be triggered by DNA damage. Moreover, cardiac glycoside drugs digoxin and ouabain inhibited the synthesis of p53 at nanomolar concentrations by activation of Src/MAPK signaling pathways via the binding to Na + /K + -ATPase.…”

Section: Discussionmentioning

confidence: 99%

Ouabain Exhibited Strong Anticancer Effects in Melanoma Cells via Induction of Apoptosis, G2/M Phase Arrest, and Migration Inhibition

Wang¹,

Cai²,

Han³

et al. 2021

OTT

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Background Malignant melanoma was characterized by insensitive chemotherapy, drug resistance, and high metastatic ability, which resulted in the main reason for the mortality among skin-related cancers. The current agents were not sufficient to improve the treatment status of melanoma patients, and it was still needed to develop new chemotherapeutic drugs for melanoma. Our study aimed to study the anticancer effects and potential mechanisms of ouabain on melanoma cells. Methods The inhibitory effects of ouabain were determined by CCK8 and colony formation assays, and the morphological changes of melanoma cells were observed by inverted microscope. The apoptosis induction and cell cycle distribution were detected by annexin V/PI double staining and PI staining, respectively. The expression of the biomarker proteins in apoptosis and G2/M phase were determined by Western blotting analysis. The effects of ouabain on the migration of melanoma cells were measured by transwell migration assay and wound closure analysis. The potential mechanisms of ouabain in melanoma cells were analyzed by transcriptome sequencing. Results Our present study demonstrated that ouabain exhibited strong inhibitory effects on cell proliferation and triggered dramatical morphological changes of melanoma cells. Moreover, ouabain induced significant apoptosis in A375 rather than SK-Mel-28 cells via upregulation of bax expression and downregulation of bcl-2 expression. Consistently, ouabain treatment induced cell cycle arrest at G2/M phase in both A375 and SK-Mel-28 cells via upregulation of cyclin B1 and downregulation of cdc2 and cdc25c. Importantly, ouabain suppressed the migration of A375 and SK-Mel-28 cells. Furthermore, the transcriptome sequencing demonstrated that p53 and MAPK signaling pathway might play important roles in the inhibitory effects of ouabain. Conclusion Our study revealed that ouabain exhibited dramatical anticancer effects, which provided a novel application for cardiac glycoside drugs in the clinical treatment of melanoma.

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DNA damage after intracerebroventricular injection of ouabain in rats

Cited by 5 publications

References 37 publications

Animal models of bipolar mania: The past, present and future

Animal models of bipolar mania: The past, present and future

A Hydroalcoholic Extract from the Leaves of Nerium oleander Inhibits Glycolysis and Induces Selective Killing of Lung Cancer Cells

Ouabain Exhibited Strong Anticancer Effects in Melanoma Cells via Induction of Apoptosis, G2/M Phase Arrest, and Migration Inhibition

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