Glutathione monoethyl ester protects against glutathione deficiencies due to aging and acetaminophen in mice.
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 monoethyl ester (GSH-OEt) can correct these deficiencies. Mice of different ages (3-31 months) through the life span were sacrificed 2 h after i.p. injection of GSH-OEt (10 mmol/kg). In separate experiments, old mice (30-31 months) 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 GSH synthesis. Liver and kidney samples were analyzed for GSH and Cys by HPLC. The hepatic GSH and renal cortical GSH and Cys concentrations were about 30% lower in old mice (30-31 months) compared to mature mice (12 months). GSH-OEt corrected these aging-related decreases. APAP decreased both hepatic 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 APAP-induced decreases in old mice.
Chen
T S
TS
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. tschen01@gwise.louisville.edu
Richie
J P
JP
Nagasawa
H T
HT
Lang
C A
CA
D000082:Acetaminophen / Q000633:toxicity*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D019328:Buthionine Sulfoximine / Q000633:toxicity; D003545:Cysteine / Q000172:deficiency / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000082:Acetaminophen; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D005978:Glutathione; D003545:Cysteine