Ts. Chen et al., Glutathione monoethyl ester protects against glutathione deficiencies due to aging and acetaminophen in mice, MECH AGE D, 120(1-3), 2000, pp. 127-139
Our previous results indicated that glutathione (GSH) and/or cysteine (Cys)
deficiency occurs in many aging tissues and also after acetaminophen (APAP
) administration. The aim of this study was to investigate whether GSH mono
ethyl ester (GSH-OEt) can correct these deficiencies. Mice of different age
s (3-31 months) through the life span were sacrificed 2 h after i.p. inject
ion of GSH-OEt (10 mmol/kg). In separate experiments, old mice (30-31 month
s) received the same dose of ester 30 min before the administration of APAP
(375 mg/kg) or buthionine sulfoximine (BSO, 4 mmol/kg), an inhibitor of GS
H biosynthesis. Liver and kidney samples were analyzed for GSH and Cys by H
PLC. The hepatic GSH and renal cortical GSH and Cys concentrations were abo
ut 30% lower in old mice (30-31 months) compared to mature mice (12 months)
. GSH-OEt corrected these aging-related decreases. APAP decreased both hepa
tic and renal cortical GSH and Cys concentrations in old mice, but GSH-OEt
prevented these decreases. GSH-OEt also prevented the BSO-induced decreases
in hepatic and renal GSH concentrations. The results demonstrated that GSH
-OEt protected against GSH deficiency due to biological aging as well as AP
AP-induced decreases in old mice. (C) 2000 Published by Elsevier Science Ir
eland Ltd.