Article

Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem

Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Biological Chemistry (Impact Factor: 3.27). 02/2009; 390(3):191-214. DOI: 10.1515/BC.2009.033
Source: PubMed

ABSTRACT

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.

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Available from: Shujie Shi, Jun 12, 2014
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    • "Under severe oxidative stress, this ratio can drastically shift. It has been established that decrease in GSH, increase in GSSG levels, and decrease in the GSH/GSSG ratio, are important contributing factors to some human diseases, including diabetes mellitus, cardiovascular diseases, neurodegenerative diseases, and cancer [6] [7] [8]. Furthermore, cellular GSH/GSSG redox state seems to represent an important component of malignant cell survival [9]. "
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    • "At previous studies reported that stimulation of antioxidant enzyme activities such as glutathione by ozone prepared the tissue against the effects of reactive oxygen species [21] [22]. GSH plays a particularly important role in the maintenance and regulation of the thiol-redox status of the cell [23]. Tissue GSH depletion is one of the primary factors permitting kidney tissue damage is associated with oxidative stress caused by Mtx in our study. "
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    ABSTRACT: Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.
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    • "Antioxidants are beneficial health substances because of their vital role against different diseases and disorders (Budhiyanti et al., 2011; Prasong, 2011; Saboo et al., 2011). Cellular concentration of glutathione may decreased in association with the processes of aging and pathogenesis of many diseases (Mahmoudabad et al., 2008) and on another hand, its level may affected by the growth, nutritional status and hormonal/stress levels (Ballatori et al., 2009). To our knowledge, there is no research conducted before to detect the oxidative stress on kidney tissue associated with osteoarthritis regulated with zerumbone administration. "
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