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June 15, 2018Biology of Sex DifferencesOpen Access

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

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Key result

Exogenous 17β-estradiol suppressed doxorubicin-induced cardiotoxicity in ovariectomized rats, and treatment during proestrus worsened cardiac damage compared to estrus and diestrus.

Why the study?

Does estrous-staged treatment and exogenous 17β-estradiol suppress doxorubicin-induced cardiotoxicity in female tumor-bearing spontaneously hypertensive rats?

Population

Female SST-2 tumor-bearing spontaneously hypertensive rats (SHRs) and ovariectomized SHRs (ovaSHRs)

Comparison

Estrous-staged doxorubicin treatment and… vs Saline, doxorubicin alone, dexrazoxane alone, or…

Design

Preclinical

Follow-up

13 days

Authors

KPKaytee PokrzywinskiNOAA National Centers for Coastal Ocean ScienceTBThomas BielCenter for Drug Evaluation and ResearchERElliot T. RosenUnited States Food and Drug Administration

Discussion

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Implication

May inform preclinical doxorubicin timing by cycle stage; leaves open translation to human cardiotoxicity prevention.

Structured PICO

Does estrous-staged treatment and exogenous 17β-estradiol suppress doxorubicin-induced cardiotoxicity in female tumor-bearing spontaneously hypertensive rats?

P
Population
Female SST-2 tumor-bearing spontaneously hypertensive rats and ovariectomized rats evaluated for doxorubicin-induced cardiotoxicity.
I
Intervention
Estrous-staged doxorubicin treatment (in SHRs) and exogenous 17β-estradiol (E2) and/or progesterone (P4) via time-releasing pellets prior to doxorubicin (in ovaSHRs)
C
Comparator
Saline, doxorubicin alone, dexrazoxane alone, or carrier matrix control
O
Outcome
Cardiac damage and function assessed by cardiac troponin I (cTnI), echocardiography, and histopathologysurrogate

Estrous-staged treatments and exogenous 17β-estradiol can suppress doxorubicin-induced cardiotoxicity in female tumor-bearing spontaneously hypertensive rats, suggesting a cardioprotective role for endogenous reproductive hormones.

Cite This Study

Pokrzywinski et al. (2018) studied Doxorubicin-induced cardiotoxicity. Estrous-staged doxorubicin treatment and exogenous 17β-estradiol vs. Control (saline, carrier matrix, or other estrous stages) was evaluated on Cardiac damage and function (cardiac output and cTnI). Exogenous 17β-estradiol suppressed doxorubicin-induced cardiotoxicity in ovariectomized rats, and treatment during proestrus worsened cardiac damage compared to estrus and diestrus.

synapsesocial.com/papers/6a218ec05c0c8498e2582297https://doi.org/10.1186/s13293-018-0183-9
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Also Consider

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  1. 1Estrogen Attenuates Left Ventricular and Cardiomyocyte Hypertrophy by an Estrogen Receptor–Dependent Pathway That Increases Calcineurin Degradation2008 · 150 citations
  2. 2Doxorubicin, Cardiac Risk Factors, and Cardiac Toxicity in Elderly Patients With Diffuse B-Cell Non-Hodgkin's Lymphoma2008 · 390 citations
  3. 3Potential Therapeutic Strategies for Hypertension‐Exacerbated Cardiotoxicity of Anticancer Drugs2016 · 38 citations
  4. 4Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.1996 · 165 citations
  5. 5Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats2009 · 252 citations