ArticleThe Journal of surgical research2012
Histone deacetylase inhibitor treatment attenuates MAP kinase pathway activation and pulmonary inflammation following hemorrhagic shock in a rodent model.
Article in The Journal of surgical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Adjuvant therapies for management of hemorrhagic shock: a narrative review.Critical care (London, England) · 2025Pooled it
- Bioactive Nanomaterials: Comprehensive Monitoring and Regulation of Acute Pancreatitis Induced Acute Lung Injury.International journal of nanomedicine · 2025Review
- SARS-CoV-2 Infection, Sex-Related Differences, and a Possible Personalized Treatment Approach with Valproic Acid: A Review.Biomedicines · 2022Review
- The Impact of Hemorrhagic Shock on Lung Ultrasound-Induced Pulmonary Capillary Hemorrhage.Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine · 2021Article
- Signal Pathways and Markers Involved in Acute Lung Injury Induced by Acute Pancreatitis.Disease markers · 2021Review
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Intravenous injection of post-hemorrhagic shock mesenteric lymph induces multiple organ injury in rats.Experimental and therapeutic medicine · 2019Article
- DNMT and HDAC inhibitors together abrogate endotoxemia mediated macrophage death by STAT3-JMJD3 signaling.The international journal of biochemistry & cell biology · 2018Article
- Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.The journal of trauma and acute care surgery · 2018Article
- Ac2-26, an Annexin A1 Peptide, Attenuates Ischemia-Reperfusion-Induced Acute Lung Injury.International journal of molecular sciences · 2017Article
- Inhibition of BTK protects lungs from trauma-hemorrhagic shock-induced injury in rats.Molecular medicine reports · 2017Article
- HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells.Oncotarget · 2016Article
- Article
- Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury.Journal of cell science · 2015Article
- Regulatory T cell DNA methyltransferase inhibition accelerates resolution of lung inflammation.American journal of respiratory cell and molecular biology · 2015Article
- Article
- Creating a prosurvival phenotype through a histone deacetylase inhibitor in a lethal two-hit model.Shock (Augusta, Ga.) · 2014Article
- Synergistic effects of hypertonic saline and valproic acid in a lethal rat two-hit model.The journal of trauma and acute care surgery · 2013Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHemorrhagic shock activates cellular stress signals and can lead to systemic inflammatory response, organ injury, and death. We have previously shown that treatment with histone deacetylase inhibitors (HDACIs) significantly improves survival in lethal models (60% blood loss) of hemorrhage. The aim of the current study was to examine whether these protective effects were due to attenuation of mitogen activated protein kinase (MAPK) signaling pathways, which are known to promote inflammation and apoptosis.
methodsWistar-Kyoto rats (250-300 g) were subjected to 40% blood loss and randomized to treatment with: (1) HDACI valproic acid (VPA 300 mg/kg i.v.; volume = 0.75 mL/kg), or (2) vehicle control (0.75 mL/kg of 0.9% saline). Animals were sacrificed at 1, 4, and 20 h (n = 3-4/group/timepoint), and lung samples were analyzed by Western blotting for expression of active (phosphorylated) and inactive forms of c-Jun N-terminal Kinase (JNK) and p38 MAPK. Myeloperoxidase (MPO) activity was measured in lung tissue 20 h after hemorrhage as a marker of neutrophil infiltration. Normal animals (n = 3) served as shams.
resultsHemorrhaged animals demonstrated significant increases in phosphorylated p38 at 1 h, phosphorylated JNK at 4 h, and increased MPO activity at 20 h (P < 0.05 compared with sham). VPA treatment significantly (P < 0.05) attenuated all of these changes.
conclusionsHemorrhagic shock activates pro-inflammatory MAPK signaling pathways and promotes pulmonary neutrophil infiltration, affects that are significantly attenuated by VPA treatment. This may represent a key mechanism through which HDACIs decrease organ damage and promote survival in hemorrhagic shock.
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Registered trials
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