Glutathione (GSH) is the most abundant intracellular nonprotein thiol involved in many cellular functions, including redox homeostasis buffering.
Cellular radiosensitivity has been shown to be inversely correlated with endogenous glutathione levels. A number of trials have investigated the potential role of GSH as a protective agent against cellular damage induced by radiation or exogenous chemicals.
Therefore, as an antioxidant, GSH is also considered a radioprotectant.
Multiple functions of GSH in cells
1. Antioxidant function
The antioxidant function of GSH is expressed through direct interaction with reactive oxygen species or donating electrons to other redox systems, such as glutathione peroxidase (GPX) and glutaredoxin (GRX).
2. Detoxification function
In addition to antioxidant and electron supply, GSH is required to maintain homeostasis in animals, such as detoxification by forming conjugates with poisons and inhibiting apoptosis.
3. DNA repair function
DNA double-strand breaks caused by ionizing radiation are severe damage that, if left unrepaired or incorrectly repaired, can lead to chromosomal aberrations, cell death, and mutation and cellular transformation. Studies have shown that GSH may be an important determinant of cells' ability to repair DNA damage and resist cell death.
4. Anti-radiation function
Traditionally, GSH in the nucleus has been considered as a protector of DNA and DNA-binding proteins from oxidative stress and radiation-induced damage, and studies have shown that exogenous addition of GSH can effectively reduce radiation-induced micronuclei and chromosomal aberrations in different systems .
GSH plays an important role in preventing DNA damage caused by oxidants and ionizing radiation and in preserving nuclear proteins in a reducing environment for gene transcription during cell cycle progression.
Published reports indicate that DNA repair in cells is dependent on GSH. As a single agent, GSH has been found to affect DNA damage and repair, redox regulation, and multiple cellular signaling pathways. Thus, it appears that GSH acts not only as a radioprotectant against DNA damage, but also as a modulator of DNA repair activity.