Evidence map›Paper›PMID 31692634›Full record

ArticleTrauma surgery & acute care open2019

Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock.

Umar F Bhatti, Aaron M Williams, Ranganath G Kathawate, Panpan Chang, Jing Zhou, Ben E Biesterveld, Zhenyu Wu, Julia Dahl, Baoling Liu, Yongqing Li and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Trauma surgery & acute care open, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Umar F BhattiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Aaron M WilliamsDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Ranganath G KathawateDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Panpan ChangDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Jing ZhouDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Ben E BiesterveldDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Zhenyu WuDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Julia DahlDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Baoling LiuDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Yongqing LiDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Hasan B AlamDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.

Funding

Modulation of Acetylation in the Treatment of Lethal InjuriesR01GM084127 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALAM, HASAN B · 2009 to 2019
$2.6M
NIGMS NIH HHS R01 GM084127
6 · The paper itself

Abstract

backgroundIsoform-specific histone deacetylase inhibitors (HDACIs) MC1568 and ACY1083 are comparable to the non-selective HDACI valproic acid (VPA) in improving survival in rodents undergoing lethal hemorrhage. However, the organ-specific properties of isoform-specific HDACIs have not been fully evaluated. Also, whether they can act synergistically is not known. We hypothesized that isoform-specific HDACIs are superior to VPA in attenuating intestinal injury and act synergistically when coadministered.

methodsSprague Dawley rats were hemorrhaged (40% of total blood volume) and randomized to receive (n=4 per group) (1) MC1568 (5 mg/kg), (2) ACY1083 (30 mg/kg), (3) MC1568+ACY1083 (combination: 5 mg/kg + 30 mg/kg, respectively), (4) VPA (250 mg/kg), or (5) normal saline (NS; vehicle; 250 μL). Animals were observed for 3 hours, after which blood samples were collected and samples of the ileum were harvested. Expression of interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and cytokine-induced neutrophil chemoattractant 1 (CINC-1) was assessed in the tissues using enzyme-linked immunosorbent assay. Intestinal cleaved caspase 3 (c-caspase 3) levels were assessed as a marker of apoptosis, and histologic sections of the ileum were examined for signs of bowel injury. Levels of IL-1β and TNF-α were also measured in the serum as global markers of inflammation.

resultsTreatments with MC1568, ACY1083, MC1568+ACY1083, and VPA were associated with decreased IL-1β levels in the intestine and serum compared with NS. IL-1β and TNF-α levels were significantly lower in the ACY1083 group compared with the VPA group. CINC-1 levels were significantly lower in the isoform-specific HDACI groups compared with the NS; however, no significant differences were seen with VPA. All treatment groups had a lower expression of intestinal c-caspase 3 compared with NS. Furthermore, MC1568 and ACY1083 groups had lower apoptosis compared with the VPA group. Bowel injury scores were significantly lower in the isoform-specific HDACI groups compared with the NS group; however, the attenuation in the VPA-treated animals did not reach statistical significance. DISCUSSION: Isoform-specific HDACIs provide superior intestinal protection compared with VPA in a rodent model of hemorrhagic shock. LEVEL OF EVIDENCE: Preclinical study.

Indexed as

hemorrhagic shockhistone deacetylase inhibitorsinflammationintestine

Identifiers

PMID31692634
PMCPMC6804098

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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.