Glutathione monoethyl ester protects against glutathione deficiencies due to aging and acetaminophen in mice

Glutathione monoethyl ester protects against glutathione deficiencies due to aging and acetaminophen in mice
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DOI:
10.1016/s0047-6374(00)00214-1
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发表时间:
2000-12-01
影响因子:
5.3
通讯作者:
Lang, CA
Lang, CA
中科院分区:
医学3区
文献类型:
--
作者:
Chen, TS;Richie, JP;Lang, CA

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我们之前的结果表明,谷胱甘肽 (GSH) 和/或半胱氨酸 (Cys) 缺乏症发生在许多衰老组织中,并且在施用对乙酰氨基酚 (APAP) 后也会发生。本研究的目的是调查谷胱甘肽单乙酯 (GSH-OEt) 是否可以纠正这些缺陷。腹膜内注射后2小时处死整个生命周期中不同年龄(3-31个月)的小鼠。注射 GSH-OEt (10 mmol/kg)。在单独的实验中,老年小鼠(30-31 个月)在给予 APAP(375 mg/kg)或丁硫氨酸亚砜亚胺(BSO,4 mmol/kg)(一种 GSH 生物合成抑制剂)前 30 分钟接受相同剂量的酯。通过 HPLC 分析肝脏和肾脏样品中的 GSH 和 Cys。与成熟小鼠(12 个月)相比,老年小鼠(30-31 个月)的肝脏 GSH 和肾皮质 GSH 和 Cys 浓度大约低 30%。 GSH-OEt 纠正了这些与衰老相关的下降。 APAP 降低了老年小鼠的肝和肾皮质 GSH 和 Cys 浓度,但 GSH-OEt 阻止了这些降低。 GSH-OEt 还可以防止 BSO 引起的肝脏和肾脏 GSH 浓度降低。结果表明,GSH-OEt 可以防止由于生物衰老以及 APAP 引起的老年小鼠 GSH 缺乏而导致的 GSH 缺乏。 (C) 2000 年,爱思唯尔科学爱尔兰有限公司出版。
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 biosynthesis. 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. (C) 2000 Published by Elsevier Science Ireland Ltd.