Yoji Nanba, Noriko Watanabe, Henrik Suzukia 
Abstract
Doxorubicin (Dox) is a widely used chemotherapy drug, but its application is associated with cardiotoxicity. It was reported that doxorubicin-induced cardiotoxicity is mediated through oxidative stress coupled with impaired NO bioavailability and NF-κB activation. We investigated the effect of sequence administration of Doxorubicin on the severity of cardiotoxicity. Sprague Dawley rats were divided into three groups (n = 8) and followed for a total of 12 weeks: a) control-PBS-treated, b) Doxorubicin treated, and c) Doxorubicin + Heparin treated. Doxorubicin was administered via intraperitoneal injection 3.0 mg/kg at weekly intervals from week 2 through week 7. Heparin was administered via intraperitoneal injection. Cardiac function was assessed by echocardiography. At the end of the experiment, the rats were killed. Cardiac enzyme indexes were measured in serum. Heart tissues were processed for determination of NF-κB protein expression, glutathione (GSH), lipid peroxide (TBARS) levels and superoxide production, troponin-T (TnT) in effluate from the isolated hearts, and MCP-1 in both myocarial tissue and serum. Dox-treated mice exhibited severe cardiac dysfunction, and the mortality was higher than that in PBS-treated mice. In Dox-treated mice, the NF-κB protein expression was higher and the fibrotic areas were larger than in PBS-treated mice. The cardiotoxic effects of Dox were ameliorated by treatment with heparin. Our concluded that heparin protects heart from Dox-induced cardiotoxicity by reduced NF-κB protein expression and inflammatory mediators.
Keywords: Doxorubicin; Heparin; Cardiotoxicity; NF-κB
Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.
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