减轻阿霉素所致肝毒性

Dorsaf Bengaied, A. Ribeiro, M. Amri, D. Scherman, P. Arnaud
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引用次数: 8

摘要

阿霉素(DOX)已被用于治疗多种癌症,但其给药受到剂量依赖性毒性的限制。其对恶性细胞的细胞毒性作用已显示出增加心脏毒性、肝毒性和肾保险的风险。抗氧剂的防癌作用和DOX毒性的化学调节作用已被广泛研究。白藜芦醇(Resveratrol, RSV)是一种多酚类成分,主要存在于葡萄和葡萄酒中,近年来人们对其抗癌潜力进行了广泛的研究,揭示了其在体内和体外对不同癌细胞系的抗增殖作用。RSV还通过多种信号通路对细胞凋亡、迁移和生长具有调节作用。虽然RSV具有很大的药用价值,但其作为治疗药物的应用有限。口服生物利用度低和水溶性差等问题使RSV成为治疗目的的不可靠候选者。此外,RSV的快速胃肠道消化也是其临床转化的主要障碍。因此,为了克服这些缺点,近年来人们开始考虑基于rsv的纳米递送系统。RSV的纳米递送系统在其被上皮系统吸收以及增强到靶部位的递送方面显示出有希望的结果。在此,我们试图从DNA损伤、自由基以及RSV是否可以作为DOX的化学调节者的角度,对DOX毒性的分子机制提出新的见解。
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Reduction of Hepatotoxicity Induced by Doxorubicin
Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance. Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DOx.
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