Department of Drug Sciences, School of Pharmacy, G. d'Annunzio University, Via dei Vestini 31, 66100 Chieti, Italy.
Molecules. 2010 Mar 3;15(3):1242-64. doi: 10.3390/molecules15031242.
Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF), as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis.
还原型谷胱甘肽（GSH）是哺乳动物细胞中含量最丰富的非蛋白巯基化合物，也是几种外源物质代谢和抗氧化防御酶的首选底物。它在许多细胞过程中发挥着重要作用，如细胞分化、增殖和凋亡。在衰老和广泛的病理状态下，包括神经退行性疾病和囊性纤维化（CF），以及几种病毒感染中，都观察到 GSH 缺乏。由于其不利的生化和药代动力学特性，GSH 作为治疗剂的应用受到限制。一些报告提供了使用 GSH 前药的证据，这些前药能够补充细胞内 GSH 水平。这篇综述讨论了通过提供能够比 GSH 更容易穿过细胞膜并为 GSH 合成提供硫醇源的可逆生物缀合物来增加 GSH 水平的不同策略。
