ArticleBritish journal of pharmacology2008
Effects of levo- and dextrosimendan on NF-kappaB-mediated transcription, iNOS expression and NO production in response to inflammatory stimuli.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Effect of levosimendan on mortality in severe sepsis and septic shock: a meta-analysis of randomised trials.BMJ open · 2018Pooled it
- Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling.Biomedicines · 2024Article
- Insampaedok-San Extract Exerts an Immune-Enhancing Effect through NF-BioMed research international · 2023Article
- Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.Biomedicines · 2022Article
- Inodilators in septic shock: should these be used?Annals of translational medicine · 2020Review
- Retracted Article: Anti-inflammatory potency ofRSC advances · 2019Article
- Levosimendan pretreatment improves survival of septic rats after partial hepatectomy and suppresses iNOS induction in cytokine-stimulated hepatocytes.Scientific reports · 2019Article
- Prunus cerasoides fruit extract ameliorates inflammatory stress by modulation of iNOS pathway and Th1/Th2 immune homeostasis in activated murine macrophages and lymphocytes.Inflammopharmacology · 2018Article
- Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Screening of an FDA-approved compound library identifies levosimendan as a novel anti-HIV-1 agent that inhibits viral transcription.Antiviral research · 2017Article
- Levosimendan for Septic Myocardial Dysfunction: Not Yet Ready for Prime Time.Critical care medicine · 2015Article
- Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice.Critical care (London, England) · 2015Article
- Inotropes and inodilators for acute heart failure: sarcomere active drugs in focus.Journal of cardiovascular pharmacology · 2014Review
- Levosimendan in critical illness: a literature review.Journal of clinical medicine research · 2014Review
- Effects of combined levosimendan and vasopressin on pulmonary function in porcine septic shock.Inflammation · 2012Article
- Levosimendan attenuates pulmonary vascular remodeling.Intensive care medicine · 2011Article
- TNFα in myocardial ischemia/reperfusion, remodeling and heart failure.Heart failure reviews · 2011Review
- Treatment with levosimendan in an experimental model of early ventilator-induced diaphragmatic dysfunction.Drug target insightsArticle
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLevosimendan is used in the treatment of decompensated heart failure. It increases the contractility of the myocardium by sensitizing troponin C to calcium. In addition, levosimendan has been reported to have beneficial effects in experimental models of septic shock. Because heart failure and sepsis have been associated with excessive nitric oxide (NO) production through inducible NOS (iNOS), we investigated the effects of the simendans on NO production and iNOS expression and on generation of pro-inflammatory cytokines. EXPERIMENTAL APPROACH: Macrophages and fibroblasts were exposed to inflammatory stimuli to induce iNOS expression. Proteins were measured by western blot and mRNA expression was determined by quantitative RT-PCR. Promoter activity and nuclear factor-kappaB (NF-kappaB) and the gamma-activated site (GAS; binding site for signal transducer and activator of transcription 1; STAT1)-mediated transcription were investigated using luciferase reporter constructs. Cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA. KEY
resultsLevosimendan and dextrosimendan decreased NO production in a dose-dependent manner in cells exposed to inflammatory stimuli. The simendans decreased iNOS protein and mRNA expression but did not affect iNOS mRNA decay. These compounds decreased iNOS promoter activity and inhibited NF-kappaB-mediated transcription but not that mediated by STAT1/GAS. The simendans reduced IL-6 production slightly but they had no effect on TNF-alpha synthesis. CONCLUSIONS AND IMPLICATIONS: The simendans downregulated NF-kappaB-dependent transcription and decreased iNOS promoter activity, iNOS expression and NO production. These mechanisms may contribute to their beneficial clinical effects.
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Registered trials
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