Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis.
Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis.
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DOI：
10.3390/md14120231
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发表时间：
2016-12-20
期刊：
影响因子：
5.4
通讯作者：
Ge JB
中科院分区：
文献类型：
--
作者：
Guo JJ;Ma LL;Shi HT;Zhu JB;Wu J;Ding ZW;An Y;Zou YZ;Ge JB
阿霉素（DOX）是一种高效的化疗药物，但其使用受到剂量依赖性心脏毒性的限制。DOX诱导的心脏毒性涉及增加的氧化应激和激活的内质网介导的细胞凋亡。藻酸寡糖（AOS）是一种无免疫原性、无毒、可生物降解的高分子，具有抗氧化、抗炎和抗内质网应激等特性。本研究探讨了AOS预处理是否可以保护急性DOX心脏毒性，其机制主要集中在氧化应激和内质网介导的细胞凋亡。结果表明，AOS预处理能显著提高DOX损伤小鼠的存活率，改善DOX所致的心功能不全，减轻DOX所致的心肌细胞凋亡。AOS预处理减轻了DOX诱导的心脏氧化应激，表现为gp 91（phox）和4-羟基壬烯醛（4-HNE）的表达降低。此外，AOS预处理显著降低Caspase-12、C/EBP同源蛋白（CHOP）（内质网介导的凋亡的标志物）和Bax（CHOP的下游分子）的表达，而上调抗凋亡蛋白Bcl-2的表达。总之，这些发现确定AOS作为一种有效的化合物，防止急性DOX心脏毒性，至少部分，通过抑制氧化应激和内质网介导的细胞凋亡。
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.
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影响因子：
4.3
作者：
Csordas, Gyoergy;Hajnoczky, Gyoergy
通讯作者：
Hajnoczky, Gyoergy
影响因子：
--
作者：
Alshabanah OA;Hafez MM;Al-Harbi MM;Hassan ZK;Al Rejaie SS;Asiri YA;Sayed-Ahmed MM
通讯作者：
Sayed-Ahmed MM
影响因子：
3.5
作者：
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通讯作者：
Barton, Elisabeth R.
影响因子：
37.8
作者：
Li DL;Wang ZV;Ding G;Tan W;Luo X;Criollo A;Xie M;Jiang N;May H;Kyrychenko V;Schneider JW;Gillette TG;Hill JA
通讯作者：
Hill JA
影响因子：
20.1
作者：
Ky B;Vejpongsa P;Yeh ET;Force T;Moslehi JJ
通讯作者：
Moslehi JJ