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

American Journal of Physiology. Heart and Circulatory Physiology
Yanhe LueChristina Wang

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, c...Continue Reading

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Citations

Aug 6, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Bérénice A Benayoun, Changhan Lee
Mar 28, 2020·Circulation Research·Kendall B WallacePaulo J Oliveira
Jun 8, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Andreas M BeyerJavid Moslehi
Sep 15, 2020·Journal of Cellular Biochemistry·Shishir UpadhyayMonisha Dhiman
Dec 16, 2019·Biochemical and Biophysical Research Communications·Xiaoxue YuTao Shen
Oct 29, 2020·Oxidative Medicine and Cellular Longevity·Li ZhangLingmei Qian
Oct 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Agata KodrońAgnieszka Chacińska
Aug 28, 2021·International Journal of Molecular Sciences·Siarhei A DabravolskiAlexander N Orekhov

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Methods Mentioned

BETA
PCR
Protein Assay

Key Resources (RRID) Mentioned

AB_261817
AB_2721818

Software Mentioned

Vevo2100
Systat
SigmaStat
Qiagen

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