ArticleThe journal of trauma and acute care surgery2018
Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.
Article in The journal of trauma and acute care surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting Inflammation After Hemorrhagic Shock as a Molecular and Experimental Journey to Improve Outcomes: A Review.Cureus · 2025Review
- Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis.Surgery open science · 2023Article
- Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety.Molecules (Basel, Switzerland) · 2022Article
- Differential Expression of Zinc-Dependent HDAC Subtypes and their Involvement in Unique Pathways Associated with Carcinogenesis.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Article
- Mitochondrial antioxidant SkQ1 decreases inflammation following hemorrhagic shock by protecting myocardial mitochondria.Frontiers in physiology · 2022Article
- Management of non-compressible torso hemorrhage: An update.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2021Review
- Identification of unique subtype-specific interaction features in Class II zinc-dependent HDAC subtype binding pockets: A computational study.Journal of biosciences · 2021Article
- Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Recent progress on cheminformatics approaches to epigenetic drug discovery.Drug discovery today · 2020Review
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation.The journal of trauma and acute care surgery · 2019Article
- Next-generation of selective histone deacetylase inhibitors.RSC advances · 2019Review
- Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock.Trauma surgery & acute care open · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHemorrhage is a leading preventable cause of death. Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). The HDACs can be divided into four functional classes (I, IIa/IIb, III, and IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with nonselective HDACIs.
methodsSurvival study: Sprague-Dawley rats were subjected to lethal HS (50% hemorrhage) and randomized to the following groups (n = 8): (1) no treatment, (2) normal saline vehicle, (3) cyclodextrin vehicle, (4) MS275 (class I HDACI), (5) VPA (class I/IIa HDACI), (6) MC1568 (class IIa HDACI), (7) ACY1083 (class IIb HDACI), and (8) EX527 (class III HDACI). Survival was monitored for 24 hours. Mechanistic study: Sprague-Dawley rats were subjected to sublethal HS (40% hemorrhage) and randomized to the same groups (n = 3), excluding EX527, based on results of the survival study. Tissues were harvested at 3 hours posttreatment, and expression of phosphorylated-AKT, β-catenin, acetylated histones H3 and H4, and acetylated α-tubulin were analyzed in myocardial tissue.
resultsSurvival rate was 12.5% in the untreated group, and did not improve with vehicle or MS275 treatment. EX527 improved survival to 50%, although this did not achieve statistical significance (p = 0.082). However, treatment with VPA, MC1568, and ACY1083 improved survival rates to 87.5%, 75%, and 75%, respectively (p < 0.05). The VPA-induced acetylation of both histones H3 and H4, while MC1568 and ACY1083 increased acetylation of histone H4. ACY1083 also induced acetylation of α-tubulin. All treatment groups, except MS275, increased phosphorylated-AKT, and β-catenin.
conclusionInhibition of HDAC classes IIa or IIb, but not class I, activates prosurvival pathways, which may be responsible for the improved outcomes in rodent models of HS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.