TRANSPORT AND METABOLISM OF GLUTATHIONE ISOPROPYL ESTER IN CEREBROSPINAL-FLUID

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimat ed by levels Of GSH or GSH isopropyl ester and their metabolites in CS F 30 min after the intravenous administration of GSH or GSH isopropyl eater (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 cont rols. On the other hand, treatment with GSH had no significant increas e in GSH levels in CSF but increased its metabolite levels, such as cy steinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glut amyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stabl e than GSH in CSF. These results are compatible with our previous repo rt (Yamamoto et al. (1993) showing that the protective action of GSH i sopropyl 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 inc reasing GSH levels in the CSF.