Autor: |
Jun-Jie Guo, Lei-Lei Ma, Hong-Tao Shi, Jian-Bing Zhu, Jian Wu, Zhi-Wen Ding, Yi An, Yun-Zeng Zou, Jun-Bo Ge |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
|
Zdroj: |
Marine Drugs, Vol 14, Iss 12, p 231 (2016) |
Druh dokumentu: |
article |
ISSN: |
1660-3397 |
DOI: |
10.3390/md14120231 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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