Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity.

Authors:
Michela Pecoraro
Michela Pecoraro
School of Pharmacy
Lawrence | United States
Stefania Marzocco
Stefania Marzocco
University of Salerno
Italy
Rosalinda Sorrentino
Rosalinda Sorrentino
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

Toxicol Appl Pharmacol 2016 Feb 11;293:44-52. Epub 2016 Jan 11.

Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. Electronic address:

Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24h after a single injection of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy.

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Source
http://dx.doi.org/10.1016/j.taap.2016.01.006DOI Listing
February 2016
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14 Citations
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