Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment.

Authors:
Michela Pecoraro
Michela Pecoraro
School of Pharmacy
Lawrence | United States
Stefania Marzocco
Stefania Marzocco
University of Salerno
Italy
Michele Ciccarelli
Michele Ciccarelli
University of Salerno
Fisciano | Italy
Prof. Guido Iaccarino, MD, PhD
Prof. Guido Iaccarino, MD, PhD
Federico II University of Naples
Full Professor of Applied Medical Science and Technology
Cardiology
Napoli, Campania | Italy
Aldo Pinto
Aldo Pinto
University of Salerno
Italy
Ada Popolo
Ada Popolo
University of Salerno
Italy

Int J Mol Sci 2017 Oct 11;18(10). Epub 2017 Oct 11.

Department of Pharmacy, University of Salerno, Fisciano (SA) 84084, Italy.

The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca-ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.

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http://dx.doi.org/10.3390/ijms18102121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666803PMC

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October 2017
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References

(Supplied by CrossRef)
Pathogenesis and prevention of doxorubicin cardiomyopathy
Ferrans et al.
Tsitologiya 1997
Cardiotoxicity of 5 fluorouracil: Ischemia or myocardial toxicity?
Medrano et al.
Rev. Clin. Esp. 2001

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