Mar. Drugs 2016, 14(12), 231; doi:10.3390/md14120231
Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis
Jun-Jie Guo 1,2,†, Lei-Lei Ma 1,†, Hong-Tao Shi 1,†, Jian-Bing Zhu 1,†, Jian Wu 1
, Zhi-Wen Ding 1, Yi An 2, Yun-Zeng Zou 1,3,*
and Jun-Bo Ge 1,3,*
, Zhi-Wen Ding 1, Yi An 2, Yun-Zeng Zou 1,3,*
and Jun-Bo Ge 1,3,*
1
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China
2
Department of Cardiology, The Affiliated Hospital of Qingdao University, 16 Jiang Su Road, Qingdao 266003, China
3
Institute of Biomedical Science, Fudan University, Shanghai 200032, China
â€
The first four authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Received: 11 September 2016 / Revised: 7 December 2016 / Accepted: 9 December 2016 / Published: 20 December 2016
Abstract
Doxorubicin (DOX) is a highly potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. DOX-induced cardiotoxicity involves increased oxidative stress and activated endoplasmic reticulum-mediated apoptosis. Alginate oligosaccharide (AOS) is a non-immunogenic, non-toxic and biodegradable polymer, with anti-oxidative, anti-inflammatory and anti-endoplasmic reticulum stress properties. The present study examined whether AOS pretreatment could protect against acute DOX cardiotoxicity, and the underlying mechanisms focused on oxidative stress and endoplasmic reticulum-mediated apoptosis. We found that AOS pretreatment markedly increased the survival rate of mice insulted with DOX, improved DOX-induced cardiac dysfunction and attenuated DOX-induced myocardial apoptosis. AOS pretreatment mitigated DOX-induced cardiac oxidative stress, as shown by the decreased expressions of gp91 (phox) and 4-hydroxynonenal (4-HNE). Moreover, AOS pretreatment significantly decreased the expression of Caspase-12, C/EBP homologous protein (CHOP) (markers for endoplasmic reticulum-mediated apoptosis) and Bax (a downstream molecule of CHOP), while up-regulating the expression of anti-apoptotic protein Bcl-2. Taken together, these findings identify AOS as a potent compound that prevents acute DOX cardiotoxicity, at least in part, by suppression of oxidative stress and endoplasmic reticulum-mediated apoptosis. View Full-TextKeywords:
alginate oligosaccharide; doxorubicin cardiotoxicity; oxidative stress; endoplasmic reticulum; apoptosis
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Guo, J.-J.; Ma, L.-L.; Shi, H.-T.; Zhu, J.-B.; Wu, J.; Ding, Z.-W.; An, Y.; Zou, Y.-Z.; Ge, J.-B. Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis. Mar. Drugs 2016, 14, 231.
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