Shikama H, Ohta A, Iwai A, Koutoku H, Umeda M, Noguchi K, Takeda M, Ohhata I
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Res Commun Mol Pathol Pharmacol. 1995 Jun;88(3):349-57.
The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.
通过静脉注射谷胱甘肽（GSH）或谷胱甘肽异丙酯（300mg/kg）30分钟后，测定大鼠脑脊液（CSF）中GSH或谷胱甘肽异丙酯及其代谢产物的水平，来评估GSH或谷胱甘肽异丙酯向脑脊液的转运情况。尽管脑脊液对谷胱甘肽异丙酯的摄取量几乎与GSH相等，脑脊液中非蛋白巯基含量增加约两倍可证明这一点，但与生理盐水处理的对照组相比，谷胱甘肽异丙酯处理后脑脊液中谷胱甘肽异丙酯和GSH浓度之和增加了32%。另一方面，用GSH处理后，脑脊液中GSH水平没有显著增加，但增加了其代谢产物水平，如半胱氨酰甘氨酸和半胱氨酸。谷胱甘肽异丙酯的代谢比GSH少。谷胱甘肽异丙酯对纯化的γ-谷氨酰转肽酶（脉络丛中GSH代谢的关键酶）亲和力低，这支持了谷胱甘肽异丙酯在脑脊液中比GSH更稳定的发现。这些结果与我们之前的报告（Yamamoto等人，1993年）一致，该报告表明谷胱甘肽异丙酯对大鼠脑缺血的保护作用大于GSH。谷胱甘肽异丙酯可能是一种有用的药物，通过提高脑脊液中的GSH水平来保护大脑免受与氧相关毒性相关的损伤。
