OXIGLUTATIONE DISODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H28N6O12S2.2Na.2H
Molecular Weight	656.595
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H+].[H+].[Na+].[Na+].N[C@@H](CCC(=O)N[C@@H](CSSC[C@H](NC(=O)CC[C@H](N)C([O-])=O)C(=O)NCC([O-])=O)C(=O)NCC([O-])=O)C([O-])=O

InChI

InChIKey=DRFILBXQKYDTFW-JIWRMXRASA-L

InChI=1S/C20H32N6O12S2.2Na/c21-9(19(35)36)1-3-13(27)25-11(17(33)23-5-15(29)30)7-39-40-8-12(18(34)24-6-16(31)32)26-14(28)4-2-10(22)20(37)38;;/h9-12H,1-8,21-22H2,(H,23,33)(H,24,34)(H,25,27)(H,26,28)(H,29,30)(H,31,32)(H,35,36)(H,37,38);;/q;2*+1/p-2/t9-,10-,11-,12-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: https://pubchem.ncbi.nlm.nih.gov/compound/oxiglutatione
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/6137189

Oxiglutathione is the oxidized disulfide form of glutathione (GSH) with potential protective activity. Glutathione disulfide (GSSG) is reduced by glutathione reductase to GSH. GSSG and GSH together play important roles in numerous redox reactions, such as those involved in the detoxification of harmful substances and free radicals, and in reactions preventing oxidative damage in erythrocytes. Upon ocular administration in irrigation solution, glutathione disulfide may exert a beneficial effect on the intracellular redox state of glutathione, thereby protecting the integrity and barrier function of the corneal endothelial cells.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutathione reductase 11 Target ID: CHEMBL2755 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6137189	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21 Sources: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM248780.pdf	Preventing		Approved 8429	NAVSTEL Approved Use Navstel is a sterile intraocular irrigating solution for use during all surgical procedures, including those requiring a relatively long intraocular perfusion time (e.g. vitrectomy, extracapsular cataract extraction/lens aspiration, anterior segment reconstruction, etc.). Upon ocular administration in irrigation solution, oxiglutathione disulfide exerts a beneficial effect on the intracellular redox state of glutathione, thereby protecting the integrity and barrier function of the corneal endothelial cells. Launch Date 2008

C_max

Value	Dose	Co-administered	Analyte	Population
0.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1.18 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
13 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20359856/	250 mg/kg single, intraperitoneal dose: 250 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		OXIGLUTATIONE plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	Other AEs: Increased intraocular pressure, Headache... Other AEs: Increased intraocular pressure (12%) Headache (3%) Ocular discomfort (5%) Macular edema (4%) Conjunctival hyperemia (4%) Dry eye (3%) Iritis (3%) Retinal hemorrhage (3%) Vision blurred (2%) Posterior capsule opacification (2%) Cataract (11%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf

AEs

AE	Significance	Dose	Population
Cataract	11%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Increased intraocular pressure	12%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Posterior capsule opacification	2%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Vision blurred	2%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Dry eye	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Headache	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Iritis	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Retinal hemorrhage	3%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Conjunctival hyperemia	4%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Macular edema	4%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf
Ocular discomfort	5%	10 mL single, intraocular Dose: 10 mL Route: intraocular Route: single Dose: 10 mL Co-administed with:: hypromellose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) dextrose(10 mL or 20 mL of intraocular irrigating solution (each mL contains: calcium chloride, magnesium chloride, dextrose, gluthathione disulfide (oxidized glutathione))) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf	unhealthy Health Status: unhealthy Condition: surgical procedures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022193lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	103239243	https://chem.nlm.nih.gov/chemidplus/id/0103239243
PubChem	76967787	https://pubchem.ncbi.nlm.nih.gov/compound/76967787

PubMed

Title	Date	PubMed
Time-dependent oxidative stress caused by benznidazole.	2001	11642718
Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats.	2001 Apr	11316323
Oxidative modification of H-ras: S-thiolation and S-nitrosylation of reactive cysteines.	2001 Apr 1	11256959
Effects of aging on the susceptibility to the toxic effects of cyclosporin A in rats. Changes in liver glutathione and antioxidant enzymes.	2001 Apr 15	11295526
Non-enzymatic antioxidative defence mechanisms against reactive oxygen species in bovine-retained and not-retained placenta: vitamin C and glutathione.	2001 Aug	11555370
An integrated electrochemical capillary liquid chromatography-dual microelectrode system for bromine based reaction detection.	2001 Aug	11534588
Short- and long-term effects of dehydroascorbate in Lupinus albus and Allium cepa roots.	2001 Aug	11522912
An ion exchange liquid chromatography/mass spectrometry method for the determination of reduced and oxidized glutathione and glutathione conjugates in hepatocytes.	2001 Aug	11451650
Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis.	2001 Feb	11181815
Glutathiolation of proteins by glutathione disulfide S-oxide derived from S-nitrosoglutathione. Modifications of rat brain neurogranin/RC3 and neuromodulin/GAP-43.	2001 Feb 2	11060308
Activation of heat shock factor 1 by pyrrolidine dithiocarbamate is mediated by its activities as pro-oxidant and thiol modulator.	2001 Feb 23	11181056
In vivo and in vitro influence of selenium on DNA/RNA synthesis in spleen and lymphocytes in culture--possible mediation of changes in GSH/GSSG ratio.	2001 Jan	11349521
Interchain disulfide bonds promote protein cross-linking during protein folding.	2001 Jan	11134973
Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase.	2001 Jan	11133496
Glutathione in induced sputum of healthy individuals and patients with asthma.	2001 Jan	11120898
Effects of iron overload and lindane intoxication in relation to oxidative stress, Kupffer cell function, and liver injury in the rat.	2001 Jan 1	11141352
Prevention of acetaminophen-induced liver toxicity by 2(R,S)-n-propylthiazolidine-4(R)-carboxylic acid in mice.	2001 Jan 15	11163339
Analysis of glutathione by capillary electrophoresis based on sample stacking.	2001 Jul	11504072
Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.	2001 Jul	11446713
Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone.	2001 Jul 27	11476958
Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase.	2001 Jun	11491650
A possible role of glutathione and glutathione disulfide in tracheary element differentiation in the cultured mesophyll cells of Zinnia elegans.	2001 Jun	11427688
Hydrogen peroxide removal and glutathione mixed disulfide formation during metabolic inhibition in mesencephalic cultures.	2001 Jun	11413233
Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin.	2001 Jun	11407976
Metabolism of S-nitrosoglutathione in intact mitochondria.	2001 Jun 1	11368766
Characterization of glutathione amide reductase from Chromatium gracile. Identification of a novel thiol peroxidase (Prx/Grx) fueled by glutathione amide redox cycling.	2001 Jun 15	11399772
Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death.	2001 Jun 21	11516525
Glutathione oxidation by hypochlorous acid in endothelial cells produces glutathione sulfonamide as a major product but not glutathione disulfide.	2001 Jun 22	11283008
Putative disulfide-forming pathway of porcine insulin precursor during its refolding in vitro.	2001 Mar 6	11258877
Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stress.	2001 May	11437734
Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury.	2001 May	11299211
Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses.	2001 May 15	11369497
Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats.	2001 Nov 28	11672700
Induction of mild intracellular redox imbalance inhibits proliferation of CaCo-2 cells.	2001 Oct	11641239
Glutathione stability in whole blood: effects of various deproteinizing acids.	2001 Oct	11591901
Redox regulation of endothelial barrier integrity.	2001 Oct	11557591
COPD as a muscle disease.	2001 Oct 1	11673186
Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects.	2001 Oct 15	11595381
Application of double-impedance system and cyclic voltammetry to study the adsorption of fullerols (C60(OH)n) on biological peptide-adsorbed gold electrode.	2001 Sep	11516084

Patents

Sample Use Guides

In Vivo Use Guide

NAVSTEL solution, should be used according to the standard technique employed by the operating surgeon. Do not use NAVSTEL until Part I is fully reconstituted with Part II. Reconstitute just prior to surgery. After reconstitution, use a single patient administration set with an air-inlet in the plastic spike since the bottle does not contain a separate airway tube. Follow the directions for the particular administration set to be used. Insert the spike aseptically into the bottle through the center target area of the rubber stopper. Allow the fluid to flow to remove air from the tubing before intraocular irrigation begins. If a second bottle is necessary to complete the surgical procedure, insure that the vacuum is vented from the second bottle BEFORE attachment to the administration set.

Route of Administration: Irrigation

In Vitro Use Guide

Kinetic studies were carried out at 25 °C in a volume of 1 mL. The assay mixtures contained 100 mM potassium phosphate buffer pH 7.0, 200 mM KCl, 100 uM NADPH, and 1 mM GSSG. Inhibitor stock solutions were prepared in 100% DMSO. One % final DMSO concentration was kept constant in the assay cuvette. The reaction was started with the addition of the enzyme (8 milliunits or 1.2 pmol of FAD-containing subunit in 5 uL aliquot), and initial rates were determined from NADPH oxidation measured at 340 nm. Km for GSSG reduction was found to be 12.5 uM.

Name

Type

Language

OXIGLUTATIONE DISODIUM

Common Name

English

GLYCINE, L-.GAMMA.-GLUTAMYL-L-CYSTEINYL-, BIMOL. (2->2')-DISULPHIDE, DISODIUM SALT

Common Name

English

GLUTHOXIM

Common Name

English

NOV-002

Code

English

Oxiglutatione disodium [WHO-DD]

Common Name

English

OXIGLUTATIONE DISODIUM SALT

Common Name

English

GLUTOXIM

Common Name

English

NSC-755883

Code

English

Code System Code Type Description

FDA UNII

GY131TX61G