Evidence map›Paper›PMID 29775411›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2018

Humanin analog enhances the protective effect of dexrazoxane against doxorubicin-induced cardiotoxicity.

Yanhe Lue, Chen Gao, Ronald Swerdloff, James Hoang, Rozeta Avetisyan, Yue Jia, Meng Rao, Shuxun Ren, Vince Atienza, Junyi Yu and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 50 citations in OpenAlex.

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  10. Pharmaceutical biology · 2022
    Article
  11. Emerging mitochondrial signaling mechanisms in cardio-oncology: beyond oxidative stress.American journal of physiology. Heart and circulatory physiology · 2022
    Review
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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

15 authors at 6 institutions in 2 countries.

Yanhe LueDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
Chen GaoDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Ronald SwerdloffDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
James HoangDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
Rozeta AvetisyanDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Yue JiaDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
Meng RaoDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
Shuxun RenDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Vince AtienzaDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
Junyi YuDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Ye ZhangDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Mengping ChenDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Yang SongDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Yibin WangDivision of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Los Angeles, California.
Christina WangDivision of Endocrinology, Department of Medicine, Los Angeles Biomedical Research Institute and Harbor-UCLA Medical Center, University of California-Los Angeles, Torrance, California.
University of California, Los Angeles · USHarbor–UCLA Medical Center · USArmy Medical University · CNShanghai Jiao Tong University · CNThe Lundquist Institute · USUCLA Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
NCATS NIH HHS UL1 TR000124
6 · The paper itself

Abstract

The chemotherapeutic effect of doxorubicin (Dox) is limited by cumulative dose-dependent cardiotoxicity in cancer survivors. Dexrazoxane (DRZ) is approved to prevent Dox-induced cardiotoxicity. Humanin and its synthetic analog HNG have a cytoprotective effect on the heart. To investigate the cardioprotective efficacy of HNG alone or in combination with DRZ against Dox-induced cardiotoxicity, 80 adult male mice were randomly divided into 8 groups to receive the following treatments via intraperitoneal injection: saline dailym HNG (5 mg/kg) daily, DRZ (60 mg/kg) weekly, Dox (3 mg/kg) weekly, DRZ + HNG, Dox + HNG, Dox + DRZ, and Dox + HNG + DRZ. Echocardiograms were performed before and at 4, 8, and 9.5 wk after the beginning of treatment. All mice were euthanized at 10 wk. In the absence of Dox, HNG, DRZ, or DRZ + HNG had no adverse effect on the heart. Dox treatment caused decreases in ejection fraction and cardiac mass and increases in cardiomyocyte apoptosis and intracardiac fibrosis. HNG or DRZ alone blunted the Dox-induced decrease in left ventricle posterior wall thickness and modestly ameliorated the Dox-induced decrease in ejection fraction. HNG + DRZ significantly ameliorated Dox-induced decreases in ejection function, cardiac fibrosis, and cardiac mass. Using a targeted analysis for the mitochondrial gene array and protein expression in heart tissues, we demonstrated that HNG + DRZ reversed DOX-induced altered transcripts that were biomarkers of cardiac damage and uncoupling protein-2. We conclude that HNG enhances the cardiac protective effect of DRZ against Dox-induced cardiotoxicity. HNG + DRZ protects mitochondria from Dox-induced cardiac damage and blunts the onset of cardiac dysfunction. Thus, HNG may be an adjuvant to DRZ in preventing Dox-induced cardiotoxicity. NEW & NOTEWORTHY Doxorubicin (Dox) is commonly used for treating a wide range of human cancers. However, cumulative dosage-dependent carditoxicity often limits its clinical applications. We demonstrated in this study that treating young adult male mice with synthetic humanin analog enhanced the cardiac protective effect of dexrazoxane against chemotherapeutic agent Dox-induced cardiac dysfunction. Thus, humanin analog can potentially serve as an adjuvant to dexrazoxane in more effectively preventing Dox-induced cardiac dysfunction and cardiomyopathy.

Indexed as

AnimalsCardiotonic AgentsCardiotoxicityDexrazoxaneDoxorubicinDrug SynergismIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMyocytes, CardiacCardiotonic AgentsDexrazoxaneDoxorubicinhumaninIntracellular Signaling Peptides and Proteinscardiotoxicitydexrazoxanedoxorubicinhumanin

Identifiers

PMID29775411
PMCPMC6734085
OpenAlexW2803375047

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.