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Event: 130

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Depletion, GSH

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Depletion, GSH

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
eukaryotic cell

Organ term

Organ term
liver

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
abnormal glutathione level	glutathione	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Glutathione conjugation leading to reproductive dysfunction	KeyEvent	Leonardo Vieira (send email)	Under Development: Contributions and Comments Welcome

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Vertebrates	Vertebrates	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

GSH depletion is commonly observed in different types of organs and cells (Deneke and Fanburg 1989; Lushchak 2012; Aquilano, Baldelli, and Ciriolo 2014). One of the main roles of this antioxidant is to sequester free radicals in order to prevent cell damage. A decline in GSH levels has been thoroughly related to the increase of reactive oxygen species, as well as to lipid peroxides, culminating in tissue oxidative stress (Comporti et al. 1991; Martin and Teismann 2009; Lushchak 2012; Aquilano, Baldelli, and Ciriolo 2014).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Photocolorimetric assays (Rahman 2007; Massarsky, Kozal, and Di Giulio 2017),
HPLC (Afzal et al. 2002; J. Liu et al. 2010)
Through commercial kits purchased from specialized companies.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Plausible domain of applicability

Taxonomic applicability: The GSH depletion is known to occur in eukaryotic cells.

Life stage applicability: GSH depletion can be measured at any stage of life.

Sex applicability: GSH depletion can be measured in both male and female species.

References

List of the literature that was cited for this KE description. More help

Deneke, S. M., and B. L. Fanburg. 1989. “Regulation of Cellular Glutathione.” The American Journal of Physiology 257 (4 Pt 1): L163–73.

Lushchak, Volodymyr I. 2012. “Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions.” Journal of Amino Acids 2012 (February): 736837.

Aquilano, Katia, Sara Baldelli, and Maria R. Ciriolo. 2014. “Glutathione: New Roles in Redox Signaling for an Old Antioxidant.” Frontiers in Pharmacology 5 (August): 196.

Comporti, M., E. Maellaro, B. Del Bello, and A. F. Casini. 1991. “Glutathione Depletion: Its Effects on Other Antioxidant Systems and Hepatocellular Damage.” Xenobiotica; the Fate of Foreign Compounds in Biological Systems 21 (8): 1067–76.

Martin, Heather L., and Peter Teismann. 2009. “Glutathione--a Review on Its Role and Significance in Parkinson’s Disease.” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 23 (10): 3263–72.

Rahman, Khalid. 2007. “Studies on Free Radicals, Antioxidants, and Co-Factors.” Clinical Interventions in Aging 2 (2): 219–36.

Massarsky, Andrey, Jordan S. Kozal, and Richard T. Di Giulio. 2017. “Glutathione and Zebrafish: Old Assays to Address a Current Issue.” Chemosphere 168 (February): 707–15.

Afzal, Mohammed, Aqeela Afzal, Andrew Jones, and Donald Armstrong. 2002. “A Rapid Method for the Quantification of GSH and GSSG in Biological Samples.” Methods in Molecular Biology 186: 117–22.

Liu, Jiaofang, Chunyan Bao, Xinhua Zhong, Chunchang Zhao, and Linyong Zhu. 2010. “Highly Selective Detection of Glutathione Using a Quantum-Dot-Based OFF–ON Fluorescent Probe.” Chemical Communications 46 (17): 2971–73