Endogenous Metabolite

活细胞中最常见的非蛋白质硫醇之一是 L-还原型谷胱甘肽。生物体中重要的生物过程包括蛋白质和DNA的合成、酶活性、新陈代谢和细胞保护，所有这些都依赖于L-还原型谷胱甘肽。 L-还原型谷胱甘肽已被发现是氧化应激的标志，具有清除氧自由基的能力[1]。

GSH处理后ROS降低，肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6、基质金属蛋白酶（MMP）-1、MMP-3的mRNA水平也受到显著抑制。然而，IL-10水平增强，GSH增加PTEN的表达。GSH抑制磷酸化（p）-PI3K和p-AKT的活化。补充BSO恢复了PI3K/AKT通路的激活，产生了高活性氧。当添加BSO时，TNF-α、IL-1β和IL-6的水平也升高。[2]
结论：GSH可通过下调MH7A细胞PTEN/PI3K/AKT通路而发挥炎症抑制作用。这些数据表明GSH具有改善RA SF炎症的新功能，并可能有助于缓解RA的病理过程。[2]

已知用吸附的钴酞菁涂覆的改性电极对碱性水溶液中几种硫醇的电氧化显示出显著的电催化活性。在这种情况下，我们在本研究中探索了吸附在普通热解石墨电极上的酞菁钴（CoPc）在生理pH下对还原型L-谷胱甘肽GSH的氧化及其二硫化物GSSG的电催化活性。为此，进行了循环和旋转圆盘伏安法，电流测量结果表明，可以容易地获得具有良好再现性和灵敏度（符合生物介质中预期的GSH浓度）的稳定电化学传感材料。这为设计能够在生物相关实验条件下（就pH而言）检测这两种分析物的电化学传感器开辟了道路[1]。

MH7A细胞和小鼠SF用指定浓度的GSH（100μg/mL）加或不加大肠杆菌脂多糖（LPS）（100 ng/mL）处理，对照组用等量的磷酸盐缓冲盐水（PBS）在37°C下处理24小时。上清液通过酶联免疫吸附试验（ELISA）检测细胞因子的蛋白质水平。这些细胞用于通过逆转录定量聚合酶链式反应（RT-qPCR）检测细胞因子的信使核糖核酸（mRNA）表达水平，并用于通过蛋白质印迹测量PTEN、磷酸化（p）-PI3K和p-AKT的蛋白质表达水平[2]
根据制造商的说明，使用ROS测定试剂盒测定ROS的水平。根据制造商的说明，使用2´，7´-二氯荧光素二乙酸酯（DCFDA）测定试剂盒测量细胞ROS的产生。DCFDA是一种可渗透细胞的荧光染料，可测量细胞内的羟基、过氧基和ROS活性。简言之，用无血清培养基以1:1000的比例稀释DCFH-DA，最终浓度为10μmoL/L。取出细胞培养基，在24孔板中加入500µL稀释的DCFH-DA。在37°C的潮湿环境（5%CO2）中培养20分钟。用无血清细胞培养基冲洗细胞三次，以完全去除多余的DCFH-DA。最后，用激光共聚焦显微镜拍摄图像[2]
使用TRIzol®试剂从MH7A细胞和小鼠SF中分离RNA，并使用PrimeScript™RT Master混合物进行RT。然后，使用SYBR®Premix Ex Taq™和基因特异性引物扩增互补脱氧核糖核酸（cDNA）。RT-qPCR分析是在LightCycler®480 II检测系统中，在以下热循环条件下进行的：使用表1和表2中列出的引物，在95°C下初始变性5分钟，然后在95°C.下45次循环15秒，在60°C.下15秒，和在72°C下15秒。所有实验一式三份进行，并将比较循环阈值（Ct值）标准化为内源性参考（GAPDH）。使用2-ΔCq方法计算mRNA表达水平[2]。

A total of 30 DBA/1J female mice were used in this study. The release of ROS in MH7A cells was examined using a ROS assay kit. The effects of GSH on the messenger ribonucleic acid (mRNA) expression and protein levels of inflammatory cytokines were determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) in mouse SFs and MH7A cells, respectively. The PTEN/PI3K/AKT pathway was investigated via Western blotting. The effects of buthionine-sulfoximine (BSO), as an inhibitor of GSH, on these molecules were examined.[2]

Absorption, Distribution and Excretion
Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body.

Toxicity Summary
Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is known as a cofactor in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.

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Toxicity Data
ORL-MUS LD₅₀ 5000 mg/kg, IPR-MUS LD₅₀ 4020 mg/kg, SCU-MUS LD₅₀ 5000 mg/kg, IVN-RBT LD₅₀ > 2000 mg/kg, IMS-MUS LD₅₀ 4000 mg/kg

[1]. Electrocatalytic activity of cobalt phthalocyanine CoPc adsorbed on a graphite electrode for the oxidation of reduced L-glutathione (GSH) and the reduction of its disulfide (GSSG) at physiological pH. Bioelectrochemistry. 2007 Jan;70(1):147-54.

Glutathione is a tripeptide compound consisting of glutamic acid attached via its side chain to the N-terminus of cysteinylglycine. It has a role as a skin lightening agent, a human metabolite, an Escherichia coli metabolite, a mouse metabolite, a geroprotector, an antioxidant and a cofactor. It is a tripeptide, a thiol and a L-cysteine derivative. It is a conjugate acid of a glutathionate(1-).
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
Glutathione is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Glutathione has been reported in Zea mays, Drosophila melanogaster, and other organisms with data available.
Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) present in most mammalian tissue. Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. Glutathione is also important as a cofactor for the enzyme glutathione peroxidase, in the uptake of amino acids, and in the synthesis of leukotrienes. As a substrate for glutathione S-transferase, this agent reacts with a number of harmful chemical species, such as halides, epoxides and free radicals, to form harmless inactive products. In erythrocytes, these reactions prevent oxidative damage through the reduction of methemoglobin and peroxides. Glutathione is also involved in the formation and maintenance of disulfide bonds in proteins and in the transport of amino acids across cell membranes.
Glutathione is a compound synthesized from cysteine, perhaps the most important member of the body's toxic waste disposal team. Like cysteine, glutathione contains the crucial thiol (-SH) group that makes it an effective antioxidant. There are virtually no living organisms on this planet-animal or plant whose cells don't contain some glutathione. Scientists have speculated that glutathione was essential to the very development of life on earth. Glutathione has many roles; in none does it act alone. It is a coenzyme in various enzymatic reactions. The most important of these are redox reactions, in which the thiol grouping on the cysteine portion of cell membranes protects against peroxidation; and conjugation reactions, in which glutathione (especially in the liver) binds with toxic chemicals in order to detoxify them. Glutathione is also important in red and white blood cell formation and throughout the immune system. glutathione's clinical uses include the prevention of oxygen toxicity in hyperbaric oxygen therapy, treatment of lead and other heavy metal poisoning, lowering of the toxicity of chemotherapy and radiation in cancer treatments, and reversal of cataracts. Glutathione participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate. GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by acetaminophen, that becomes toxic when GSH is depleted by an overdose (of acetaminophen). Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein thiol groups which would otherwise be covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and renew the usable GSH pool. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
See also: Glutathione; nonapeptide-1 (component of) ... View More ...

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Drug Indication
For nutritional supplementation, also for treating dietary shortage or imbalance

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Mechanism of Action
Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It also plays a role in the hepatic biotransformation and detoxification process; it acts as a hydrophilic molecule that is added to other lipophilic toxins or wastes prior to entering biliary excretion. It participates in the detoxification of methylglyoxal, a toxic by-product of metabolism, mediated by glyoxalase enzymes. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is a cofactor of conjugation and reduction reactions that are catalyzed by glutathione S-transferase enzymes expressed in the cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.

C10H17N3O6S

307.32

307.083

C, 39.08; H, 5.58; N, 13.67; O, 31.24; S, 10.43

70-18-8

L-Glutathione reduced-13C2,15N;815610-65-2; 20167-21-9 (sodium); 34212-83-4 (disodium); 70-18-8 (free acid)

124886

Typically exists as white to off-white solids at room temperature

1.4±0.1 g/cm3

754.5±60.0 °C at 760 mmHg

182-192ºC

410.1±32.9 °C

0.0±5.5 mmHg at 25°C

1.572

-0.87

197.62

6

8

9

20

389

2

S([H])C([H])([H])[C@@]([H])(C(N([H])C([H])([H])C(=O)O[H])=O)N([H])C(C([H])([H])C([H])([H])[C@@]([H])(C(=O)O[H])N([H])[H])=O

RWSXRVCMGQZWBV-WDSKDSINSA-N

InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1

(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid

GSH; NSC-400639; NSC400639; Glutatiol; NSC 400639; L-Glutathione; Glutathione;glutathione; 70-18-8; L-Glutathione; Glutathion; L-Glutathione reduced; Isethion; Tathion; Glutathione-SH;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。  (3). 该产品在溶液状态不稳定，请现配现用。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~62.5 mg/mL (~203.37 mM)

配方 1 中的溶解度: 100 mg/mL (325.39 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。 (<60°C).

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。