Evidence map›Paper›PMID 23874823›Full record

ArticlePloS one2013

N-acetylcysteine and allopurinol confer synergy in attenuating myocardial ischemia injury via restoring HIF-1α/HO-1 signaling in diabetic rats.

Xiaowen Mao, Tingting Wang, Yanan Liu, Michael G Irwin, Jing-song Ou, Xiao-long Liao, Xia Gao, Yuan Xu, Kwok F J Ng, Paul M Vanhoutte and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

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.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 65 citations in OpenAlex.

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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 at 4 institutions in 2 countries.

Xiaowen MaoDepartment of Anaesthesiology, University of Hong Kong, Hong Kong, China.
Tingting Wang
Yanan Liu
Michael G Irwin
Jing-song Ou
Xiao-long Liao
Xia Gao
Yuan Xu
Kwok F J Ng
Paul M Vanhoutte
Zhengyuan Xia
University of Hong Kong · HKCapital Medical University · CNThe First Affiliated Hospital, Sun Yat-sen University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1α (HIF-1α)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium.

methodsControl or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicle or NAC, ALP or their combination for four weeks starting one week after STZ injection. The animals were then subjected to thirty minutes of coronary artery occlusion followed by two hours reperfusion in the absence or presence of the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1α inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1α and HO-1 achieved by gene knock-down with related siRNAs.

resultsMyocardial and plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were significantly increased in diabetic rats while cardiac HO-1 protein and activity were reduced; this was accompanied with reduced cardiac protein levels of HIF-1α, and increased post-ischemic myocardial infarct size and cellular injury. NAC and ALP given alone and in particular their combination normalized cardiac levels of HO-1 and HIF-1α protein expression and prevented the increase in 15-F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic cardiomyocyte death in vitro. However, all the above protective effects of NAC and ALP were cancelled either by inhibition of HO-1 or HIF-1α with SnPP-IX and 2ME2 in vivo or by HO-1 or HIF-1α gene knock-down in vitro.

conclusionNAC and ALP confer synergistic cardioprotection in diabetes via restoration of cardiac HIF-1α and HO-1 signaling.

Indexed as

2-MethoxyestradiolAcetylcysteineAllopurinolAnimalsAntioxidantsApoptosisCardiotonic AgentsDiabetes Mellitus, ExperimentalDinoprostDrug SynergismEchocardiographyEstradiolHeme Oxygenase (Decyclizing)Hypoxia-Inducible Factor 1, alpha SubunitIn Situ Nick-End LabelingIsoprostanes2-Methoxyestradiol8-epi-prostaglandin F2alphaAcetylcysteineAllopurinolAntioxidantsCardiotonic AgentsDinoprostEstradiolHeme Oxygenase (Decyclizing)Hif1a protein, ratHmox1 protein, ratHypoxia-Inducible Factor 1, alpha SubunitIsoprostanesMetalloporphyrinsProtoporphyrinsRNA, Small InterferingSuperoxide Dismutasetin protoporphyrin IX

Identifiers

PMID23874823
PMCPMC3715528
OpenAlexW2145397113

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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.