Oxidative stress glutathione

Oxidative stress Glutathione depletion (e.g., acetaminophen, bromoben-zene, chloroform, allyl alcohol) redox cyclers (see oxidative phosphorylation) reactive metabolites... 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

Okada et al. examined the effects of TBT on cellular content of glutathione (GSH) in rat thymocites using a flow cytometer and 5-chloromethylfluorescein diacetate, a fluorescent probe for monitoring the change in the cellular content of GSH. TBT at nanomolar concentrations reduced the cellular content of GSH. There is an important implication on the TBT-induced depletion of cellular GSH since GSH has an important role in protecting the cells against oxidative stress and chemical and metal intoxications. TBT-induced decrease in cellular content of GSH in thymocytes may increase the vulnerability of the immune system. ° ... 

Glutathione Protect Blood Cells From Oxidative Stress Damage... 

Hoffman DJ, Heinz GH. 1998. Effects of mercury and selenium on glutathione metabolism and oxidative stress in mallard ducks. Environ Toxicol Chem 17 161-166. 

Oxidant Stress-induced Alterations in Myocardial Glutathione Status... 

Although it is widely accepted that ischaemia/ reperfusion-induced oxidant stress is associated with a reduction of Na/K ATPase activity, it is difficult to determine which features of this process are responsible for this effect. A classical approach to this type of problem has been to determine the effect of the application of selected metabolites or agents on the activity of the enzyme of interest, an approach that has been exploited for the sarcolemmal Na/K ATPase and glutathione (Haddock et al., 1990). The application of GSH (O.l-l.OmM) induces a concentration-dependent increase in the activity of a bovine isolated ventricular Na/K ATPase preparation (determined by the ouabain-sensitive hydrolysis of ATP to release inorganic phosphate). In the presence of 1 mM GSH there was a 38% stimulation of activity compared to untreated control... 

Whilst experimentally it is relatively easy to investigate the eflFect of the exogenous application of GSH and GSSG on cardiac Na/K ATPase activity, one further approach that has been exploited in many aspects of oxidant-induced cell injury has been the depletion of cellular glutathione levels. The hypothesized importance of GSH in the cell s antioxidant armoury would be expected to be reflected in an increased susceptibility to oxidant stress-... 

Preliminary data, in which extracellular and intracellular glutathione status were altered in the absence of a ffee-radical-induced oxidant stress have demonstrated a similar effect on /Na/K- In these experiments the extracellular concentration of GSH was altered by varying the levels in the extracellular perfusate. In contrast, the intracellular GSH content was controlled by the inclusion of the required concentration of GSH in the patch pipette. After 5 min exposure to GSH there was an approximately 20% increase in /na/K at 0 mV. Conversely, in a separate group of cells, 5 min after the application of GSSG there was an approximately 15% decrease in /wa/K (Haddock, 1991). 

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

Jaeschke, H. (1990). Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo-, the protective effect of allopurinol. J. Pharmacol Exp. Ther. 255, 935-941. 

Neuschwander-Tetri, B.A. (1992). Hepatocyte glutathione preservation by dl-of-tocopherol during oxidant stress. Hepatology 16, 158A. 

Curello, S., Ceconi, C.. Cargnoni, A., Connacchian, A., Ferrari, R. and Albertini, A. (1987). Improved procedure for determining glutathione in plasma as an index of myocardial oxidative stress. Clin. Chem. 33, 1448-1449. 

Umemura, T., Sai, K., Takagi, A., Hasegawa, R. and Kurokawa, Y. (1991). The effects of exogenous glutathione and cysteine on oxidative stress induced by ferric nitrilo-triacetate. Cancer Lett. 58, 49-56. 

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