Clinical Application of Glutathione

Glutathione is the most common non-protein thiol in mammalian cells and the most abundant natural active peptide in eukaryotic cells. It is composed of glutamic acid, cysteine and glycine and has important physiological functions. Glutathione is widely distributed, with the highest concentration in liver cells; in plasma, it is at a low level due to its rapid catabolism; in cells, 80%~85% of glutathione is distributed in the cytoplasm, and 10%~15% is located in the mitochondria , a small part exists in the endoplasmic reticulum, nucleus and other organelles. Glutathione has two forms: reduced (GSH) and oxidized (GSSG). Under physiological conditions, the reduced form mainly exists, accounting for more than 98% of the total glutathione.

GSH has multiple functions in the human body. As an antioxidant and free radical scavenger, it maintains intracellular redox balance, defends against oxidative stress, and participates in various cell metabolisms. GSH maintains the integrity of the cell membrane by protecting the sulfhydryl group of the protein on the cell membrane in a reduced state; prevents hemoglobin from being oxidized to methemoglobin, and maintains the ability to transport oxygen normally. Regulate protein function and gene expression through thiol-disulfide exchange reaction; post-translational modification of protein through S-glutathionylation, and prevent irreversible damage to intracellular proteins due to oxidative stress. Storage of cysteine through the γ-glutamyl cycle; involved in the regulation of mitochondrial permeability transition pore opening and closing through its antioxidant properties. GSH also plays an important role in regulating cell cycle, cell proliferation, apoptosis and other cellular processes, and can regulate lymphocyte function and immune response.

Ovarian cancer is a malignant tumor that seriously threatens women's lives and health. Its incidence rate ranks third among malignant tumors of the female reproductive system. In 2020, there will be 313,959 new cases of ovarian cancer worldwide, and 207,252 deaths. head.

Chemotherapy resistance in ovarian cancer is associated with multiple mechanisms, including DNA repair, autophagy, metabolic reprogramming, multidrug resistance gene expression, epithelial-mesenchymal transition, etc. In recent years, a large number of studies have found that reduced glutathione is also involved in the drug resistance process of ovarian cancer chemotherapy. GSH has multiple roles in cells, acting as a scavenger of reactive oxygen species, an antidote for xenobiotics, and a cysteine storehouse. The biological role of GSH has two sides. On the one hand, it can maintain normal cell homeostasis; on the other hand, it can reduce the damage of chemotherapy drugs to tumor cells and promote chemotherapy resistance.

In recent years, the results of in vitro and in vivo experiments and clinical trials have shown that GSH metabolism-related targeted drugs combined with chemotherapy have initially shown the effect of improving chemotherapy resistance of ovarian cancer and reducing the recurrence rate of ovarian cancer, which has good clinical application value.

Tag: Glutathione GSH

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