Chen T S, Richie J P, Nagasawa H T, Lang C A
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
Mech Ageing Dev. 2000 Dec 1;120(1-3):127-39. doi: 10.1016/s0047-6374(00)00214-1.
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.
我们之前的研究结果表明，许多衰老组织以及对乙酰氨基酚（APAP）给药后都会出现谷胱甘肽（GSH）和/或半胱氨酸（Cys）缺乏的情况。本研究的目的是探究谷胱甘肽单乙酯（GSH-OEt）是否能够纠正这些缺乏情况。对不同年龄（3至31个月）贯穿其寿命期的小鼠腹腔注射GSH-OEt（10 mmol/kg）2小时后将其处死。在单独的实验中，老年小鼠（30至31个月）在给予APAP（375 mg/kg）或谷胱甘肽合成抑制剂丁硫氨酸亚砜胺（BSO，4 mmol/kg）前30分钟接受相同剂量的酯。通过高效液相色谱法分析肝脏和肾脏样本中的GSH和Cys。与成年小鼠（12个月）相比，老年小鼠（30至31个月）肝脏中的GSH、肾皮质中的GSH和Cys浓度大约低30%。GSH-OEt纠正了这些与衰老相关的降低情况。APAP降低了老年小鼠肝脏和肾皮质中的GSH和Cys浓度，但GSH-OEt阻止了这些降低。GSH-OEt还阻止了BSO诱导的肝脏和肾脏中GSH浓度的降低。结果表明，GSH-OEt可预防老年小鼠因生物衰老以及APAP诱导而导致的GSH缺乏。
