Rutin Protects against Pirarubicin-Induced Cardiotoxicity through TGF-β1-p38 MAPK Signaling PathwayReportar como inadecuado




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Evidence-Based Complementary and Alternative Medicine - Volume 2017 2017, Article ID 1759385, 10 pages - https:-doi.org-10.1155-2017-1759385

Research Article

Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China

The Third Hospital Affiliated to The Jinzhou Medical University, No. 5-2 Heping Road, Jinzhou, Liaoning 120001, China

Correspondence should be addressed to Liqun Ren

Received 18 October 2016; Revised 20 December 2016; Accepted 4 January 2017; Published 6 March 2017

Academic Editor: Darren R. Williams

Copyright © 2017 Yadi Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We investigated the potential protective effect of rutinum RUT against pirarubicin- THP- induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane DZR prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase MAPK inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30–70 μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 μM. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway.





Autor: Yadi Wang, Yang Zhang, Bo Sun, Qing Tong, and Liqun Ren

Fuente: https://www.hindawi.com/



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