Williamson J M, Boettcher B, Meister A
Proc Natl Acad Sci U S A. 1982 Oct;79(20):6246-9. doi: 10.1073/pnas.79.20.6246.
Depletion of glutathione by inhibition of its synthesis by buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, leads to increased sensitivity to (i) irradiation and (ii) oxidative stress. In the present work, an intracellular cysteine delivery system was used to promote glutathione synthesis, and this was found to protect against toxicity. Thus, administration of L-2-oxothiazolidine-4-carboxylate protected against acetaminophen toxicity in mice; the thiazolidine, which is converted to L-cysteine by the enzyme 5-oxo-L-prolinase (present in many animal tissues and in plants) promotes the synthesis of glutathione, which is the actual protectant. The effect of this thiazolidine in increasing the level of glutathione is prevented by administration of buthionine sulfoximine. This thiazolidine may be useful in the treatment of other toxicities and in the treatment of certain diseases. It may also be valuable as a component of amino acid mixtures used in therapy and as a safener in agriculture.
通过丁硫氨酸亚砜亚胺抑制谷胱甘肽的合成（γ-谷氨酰半胱氨酸合成酶的不可逆抑制剂），会导致对（i）辐射和（ii）氧化应激的敏感性增加。在本研究中，一种细胞内半胱氨酸递送系统被用于促进谷胱甘肽的合成，并且发现这可以防止毒性。因此，给予L-2-氧代噻唑烷-4-羧酸盐可保护小鼠免受对乙酰氨基酚的毒性；该噻唑烷可被5-氧代-L-脯氨酸酶（存在于许多动物组织和植物中）转化为L-半胱氨酸，从而促进谷胱甘肽的合成，而谷胱甘肽才是真正的保护剂。给予丁硫氨酸亚砜亚胺可阻止这种噻唑烷增加谷胱甘肽水平的作用。这种噻唑烷可能在治疗其他毒性以及某些疾病方面有用。它作为治疗中使用的氨基酸混合物的成分以及农业中的安全剂也可能有价值。
