Strategies to prevent dopamine oxidation and related cytotoxicity using various antioxidants and nitrogenation
Strategies to prevent dopamine oxidation and related cytotoxicity using various antioxidants and nitrogenation
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DOI：
10.1007/s42247-019-00037-5
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发表时间：
2019-06-01
影响因子：
3.8
通讯作者：
Bencherif, Sidi A.
中科院分区：
文献类型：
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作者：
Rana, Devyesh;Colombani, Thibault;Bencherif, Sidi A.
多巴胺 (DA) 在大脑和身体中发挥着多种重要作用，最近已被用作医疗应用的生物粘附前体。然而，DA 在暴露于氧气时立即氧化并迅速聚合成聚多巴胺 (PDA)，导致氧化应激、细胞毒性和 DA 功能丧失。因此，防止 DA 快速氧化至关重要，但仍然是一个重大挑战。在这里，我们报告了几种阻止相关水溶液（即水、PBS 和细胞培养基）中 DA 氧化的策略。一种策略是使用还原剂或抗氧化剂，例如还原型谷胱甘肽 (GSH) 和四硼酸钠（通常称为硼砂）。另一种策略是基于氮化，这是一种通过创造无氧环境来保存还原形式的 DA 的方法。我们的数据表明，GSH 和硼砂的抗氧化特性可显着降低 DA 氧化，持续时间长达 2 个月。脱氮或脱氧可进一步防止 DA 氧化，从而延长其保质期。当用哺乳动物细胞进行测试时，用 GSH 防止 DA 氧化可显着提高 3T3 成纤维细胞和 T 细胞的活力。这些结果表明，单独使用抗氧化剂或与氮化结合使用，有助于防止 DA 氧化并提高其稳定性，适用于基于细胞的研究或生物材料的设计和开发。
Dopamine (DA) plays several important roles in the brain and body and has recently been used as a bioadhesive precursor for medical applications. However, DA oxidizes immediately when exposed to oxygen and rapidly polymerizes into polydopamine (PDA), leading to oxidative stress, cytotoxicity, and loss of DA functionalities. As a result, preventing rapid oxidation of DA is of paramount importance but still remains a major challenge. Here, we report several strategies to impede DA oxidation in relevant aqueous solutions (i.e., water, PBS, and cell culture media). One strategy is based on using reducing agents or antioxidants such as glutathione in its reduced state (GSH) and sodium tetraborate (commonly known as borax). Another strategy is based on nitrogenation, a method used to preserve DA in its reduced form by creating an oxygen-free environment. Our data suggest that the antioxidant properties of GSH and borax substantially decreased DA oxidation for up to 2 months. Nitrogenation or oxygen removal further prevented DA oxidation, enhancing its shelf life for longer periods of time. When tested with mammalian cells, preventing DA oxidation with GSH dramatically improved viability of 3T3 fibroblasts and T cells. These results demonstrate that the use of antioxidants, alone or in combination with nitrogenation, can help prevent DA oxidation and improve its stability for cell-based studies or for the design and development of biomaterials.