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Sodium Ferulate Protects Against Daunorubicin-induced Cardiotoxicity by Inhibition of Mitochondrial Apoptosis in Juvenile Rats

Wu, Zhi-Juan MD, PhD; Yu, Jing MD, PhD; Fang, Qiu-Juan MD, PhD; Lian, Jia-Bian MSc; Wang, Rui-Xing MD; He, Rui-Lan MD; Lin, Mo-Jun MD, PhD

Journal of Cardiovascular Pharmacology: April 2014 - Volume 63 - Issue 4 - p 360–368
doi: 10.1097/FJC.0000000000000056
Original Article

Abstract: Daunorubicin (DNR) is a widely used chemotherapeutic agent; however, its clinical use is limited because of its cardiotoxicity. This study was aimed to investigate the protective effect of sodium ferulate (SF), an effective component from traditional Chinese herbs, against DNR-induced cardiotoxicity in juvenile rats. DNR was administered intraperitoneally to rats at the dosage of 2.5 mg·kg−1·wk−1 for 5 consecutive weeks (cumulative dose of 12.5 mg/kg) or in combination with intraperitoneal injection of SF at 50 mg·kg−1·d−1 over a period of 30 days. The animals were killed 6 days after the last injection of DNR. SF significantly ameliorated the DNR-induced cardiac dysfunction, structural damage of the myocardium, and release of lactate dehydrogenase and creatine kinase. Treatment with SF also reversed DNR-induced oxidative stress as evidenced by a decrease in malondialdehyde levels with a concomitant increase in myocardical superoxide dismutase activities. Furthermore, SF afforded significant cardioprotection against DNR-induced apoptosis in vivo and effectively suppressed the complex mitochondrion-dependent apoptotic signaling triggered by DNR. This study indicates that SF may improve cardiac function by inhibition of oxidative stress and apoptosis, thus providing a beneficial effect on the prevention of DNR-induced cardiotoxicity.

Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou, China.

Reprints: Mo-Jun Lin, MD, PhD, Department of Physiology and Pathophysiology, Fujian Medical University, 1 Xueyuan Road, Fuzhou 350108, China (e-mail: mjlin@mail.fjmu.edu.cn).

Z.-J. Wu, J. Yu, and Q.-J. Fang contributed equally to this study.

Supported by grants from the Natural Scientific Foundation of Fujian Province (2011J0506) and Doctor Startup Foundation of Fujian Medical University (2010bs007) to Z.-J. Wu and by the National Natural Science Foundation of China (NSFC 31171104) and the Key Program of Scientific Research of Fujian Medical University (09ZD010) to M.-J. Lin.

The authors report no conflicts of interest.

Received November 04, 2013

Accepted November 25, 2013

© 2014 by Lippincott Williams & Wilkins.