The Natural Carotenoid Crocetin and the Synthetic Tellurium Compound AS101 Protect the Ovary against Cyclophosphamide by Modulating SIRT1 and Mitochondrial Markers.
The Natural Carotenoid Crocetin and the Synthetic Tellurium Compound AS101 Protect the Ovary against Cyclophosphamide by Modulating SIRT1 and Mitochondrial Markers.
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DOI：
10.1155/2017/8928604
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发表时间：
2017
影响因子：
--
通讯作者：
Tatone C
中科院分区：
文献类型：
--
作者：
Di Emidio G;Rossi G;Bonomo I;Alonso GL;Sferra R;Vetuschi A;Artini PG;Provenzani A;Falone S;Carta G;D'Alessandro AM;Amicarelli F;Tatone C
癌症治疗与生殖衰老加速导致的不孕不育风险增加有关。氧化应激(OS)是卵巢毒性最强的抗癌药物环磷酰胺(CPM)引起卵巢毒性的潜在机制。OS的一个重要感受器是SIRT1，它是一种依赖NAD+的脱乙酰酶，调节细胞防御和细胞命运。本研究探讨了天然类胡萝卜素西红花酸和合成化合物AS101是否通过调节SIRT1和线粒体标志物来保护卵巢免受CPM的影响。我们发现，与单独使用CPM相比，接受西红花素+CPM的雌性CD1小鼠的原始卵泡数量增加，与AS101相似，其保护作用是已知的。CPM小鼠卵巢中SIRT1表达增加，提示OS的发生。同样，线粒体SIRT3上升，而SOD2和线粒体生物发生激活因子Pgc1-α下降，表明线粒体发生了损伤。西红花酸和AS101预防SIRT1爆发，提示保留氧化还原平衡有助于卵巢对抗CPM对卵巢的损伤。在CPM前服用西红花素或AS101的小鼠，SIRT3降低，SOD2和Pgc1-α增加，这为线粒体保护提供了证据。目前的结果提高了人们对CPM对卵巢损害的认识，并可能有助于开发癌症患者保留生育能力的干预措施。
Cancer therapies are associated with increased infertility risk due to accelerated reproductive aging. Oxidative stress (OS) is a potential mechanism behind ovarian toxicity by cyclophosphamide (CPM), the most ovotoxic anticancer drug. An important sensor of OS is SIRT1, a NAD+-dependent deacetylase which regulates cellular defence and cell fate. This study investigated whether the natural carotenoid crocetin and the synthetic compound AS101 protect the ovary against CPM by modulating SIRT1 and mitochondrial markers. We found that the number of primordial follicles of female CD1 mice receiving crocetin plus CPM increased when compared with CPM alone and similar to AS101, whose protective effects are known. SIRT1 increased in CPM mouse ovaries revealing the occurrence of OS. Similarly, mitochondrial SIRT3 rose, whilst SOD2 and the mitochondrial biogenesis activator PGC1-α decreased, suggesting the occurrence of mitochondrial damage. Crocetin and AS101 administration prevented SIRT1 burst suggesting that preservation of redox balance can help the ovary to counteract ovarian damage by CPM. Decreased SIRT3 and increased SOD2 and PGC1-α in mice receiving crocetin or AS101 prior to CPM provide evidence for mitochondrial protection. Present results improve the knowledge of ovarian damage by CPM and may help to develop interventions for preserving fertility in cancer patients.
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影响因子：
5.8
作者：
Hayun, Michal;Naor, Yaniv;Sredni, Benjamin
通讯作者：
Sredni, Benjamin
DOI：
10.1080/01635581.2013.767368
发表时间：
2013-08-01
影响因子：
2.9
作者：
D'Alessandro, Anna M.;Mancini, Andrea;Festuccia, Claudio
通讯作者：
Festuccia, Claudio
影响因子：
3.8
作者：
Ganesan, Shanthi;Keating, Aileen F.
通讯作者：
Keating, Aileen F.
藏红花衍生的类胡萝卜素在前列腺癌细胞模型中的抗肿瘤作用。
影响因子：
--
作者：
Festuccia C;Mancini A;Gravina GL;Scarsella L;Llorens S;Alonso GL;Tatone C;Di Cesare E;Jannini EA;Lenzi A;D'Alessandro AM;Carmona M
通讯作者：
Carmona M
影响因子：
3.6
作者：
Cinco R;Digman MA;Gratton E;Luderer U
通讯作者：
Luderer U