Evidence map›Paper›PMID 29907135›Full record

ArticleBiology of sex differences2018

Doxorubicin-induced cardiotoxicity is suppressed by estrous-staged treatment and exogenous 17β-estradiol in female tumor-bearing spontaneously hypertensive rats.

Kaytee L Pokrzywinski, Thomas G Biel, Elliot T Rosen, Julia L Bonanno, Baikuntha Aryal, Francesca Mascia, Delaram Moshkelani, Steven Mog, V Ashutosh Rao

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In one paragraph

Article in Biology of sex differences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Review
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  5. Review
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  9. Review
  10. Article
  11. p38δ genetic ablation protects female mice from anthracycline cardiotoxicity.American journal of physiology. Heart and circulatory physiology · 2020
    Article
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  13. Review
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

9 authors.

Kaytee L PokrzywinskiLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Thomas G BielLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Elliot T RosenLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Julia L BonannoLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Baikuntha AryalLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Francesca MasciaLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA.
Delaram MoshkelaniDivision of Process Assessment III, Office of Process and Facilities, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Steven MogCenter for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD, USA.
V Ashutosh RaoLaboratory of Applied Biochemistry, Division of Biotechnology Review and Research III, Office of Biotechnology Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg., Silver Spring, MD, 20993, USA. ashutosh.rao@fda.hhs.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDoxorubicin (DOX), an anthracycline therapeutic, is widely used to treat a variety of cancer types and known to induce cardiomyopathy in a time and dose-dependent manner. Postmenopausal and hypertensive females are two high-risk groups for developing adverse effects following DOX treatment. This may suggest that endogenous reproductive hormones can in part suppress DOX-induced cardiotoxicity. Here, we investigated if the endogenous fluctuations in 17β-estradiol (E2) and progesterone (P4) can in part suppress DOX-induced cardiomyopathy in SST-2 tumor-bearing spontaneously hypersensitive rats (SHRs) and evaluate if exogenous administration of E2 and P4 can suppress DOX-induced cardiotoxicity in tumor-bearing ovariectomized SHRs (ovaSHRs).

methodsVaginal cytology was performed on all animals to identify the stage of the estrous cycle. Estrous-staged SHRs received a single injection of saline, DOX, dexrazoxane (DRZ), or DOX combined with DRZ. OvaSHRs were implanted with time-releasing pellets that contained a carrier matrix (control), E2, P4, Tamoxifen (Tam), and combinations of E2 with P4 and Tam. Hormone pellet-implanted ovaSHRs received a single injection of saline or DOX. Cardiac troponin I (cTnI), E2, and P4 serum concentrations were measured before and after treatment in all animals. Cardiac damage and function were further assessed by echocardiography and histopathology. Weight, tumor size, and uterine width were measured for all animals.

resultsIn SHRs, estrous-staged DOX treatment altered acute estrous cycling that ultimately resulted in prolonged diestrus. Twelve days after DOX administration, all SHRs had comparable endogenous circulating E2. Thirteen days after DOX treatment, SHRs treated during proestrus had decreased cardiac output and increased cTnI as compared to animals treated during estrus and diestrus. DOX-induced tumor reduction was not affected by estrous-staged treatments. In ovaSHRs, exogenous administration of E2 suppressed DOX-induced cardiotoxicity, while P4-implanted ovaSHRs were partly resistant. However, ovaSHRs treated with E2 and P4 did not have cardioprotection against DOX-induced damage.

conclusionsThis study demonstrates that estrous-staged treatments can alter the extent of cardiac damage caused by DOX in female SHRs. The study also supports that exogenous E2 can suppress DOX-induced myocardial damage in ovaSHRs.

Indexed as

AnimalsAntibiotics, AntineoplasticCardiotoxicityCardiotoxinsCell Line, TumorDoxorubicinDrug ChronotherapyEstradiolEstrogensEstrusFemaleHumansMyocardiumNeoplasmsOvariectomyProgesteroneAntibiotics, AntineoplasticCardiotoxinsDoxorubicinEstradiolEstrogensProgesteroneTroponin IAdriamycinCardiomyopathyCardioprotectionDoxorubicinEstradiolProgesterone

Identifiers

PMID29907135
PMCPMC6003183

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Registered trials

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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.