Glutathione depletion

The effect of cellular GSH depletion on /wa/K has also been studied using this model. Guinea-pig ventricular myocytes prepared from DEM-treated animals have been used to determine the effect of glutathione depletion on /xa/K- Myocytes prepared from DEM-treated animals showed a similar profile of glutathione content modification to that previously described in experiments using sarcolemmal homogenates. GSH levels in DEM-treated were reduced from a control value of 0.2 0.04 to 0.02 0.01 nmol/1 X10 cells. Jni/k at 0 mV was reduced from a control value of 1.1 0.12 to... 

Comporti, M. (1987). Glutathione depleting agents and lipid peroxidation. Chem. Phys. Lipids 45, 143-169. 

Speisky, H., Bunou, D., Orrego, H. and Israel, Y. (1985). Lack of changes in diene conjugate levels following ethanol-induced glutathione depletion or hepatic necrosis. Res. Commun. Chem. Pathol. Pharmacol. 48, 77-90. 

Jackson, M.J., Kaiser, K., Brooke, M.H. and Edwards, RH.T. (1991). Glutathione depletion during experimental damage to skeletal muscle and its relevance to Duchenne muscular dystrophy. Clin. Sci. 80, 559-564. 

Pilon D, Roberts AE, Rickert DE. 1988b. Effect of glutathione depletion on the uptake of acrylonitrile vapors and on its irreversible association with tissue macromolecules. Toxicol Appl Pharmacol 95 265-278. 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

Isolated liver segments from starved rats exposed to 100 mg KCN/L Oxygen consumption reduced 80%, and evidence of hepatotoxicity as judged by enzyme release, glutathione depletion, and calcium accumulation in liver. Hepatotoxicity prevented by feeding rats fructose 39... 

Boulares, A.H., et al., Roles of oxidative stress and glutathione depletion in JP-8 jet fuel-induced apoptosis in rat lung epithelial cells, Toxicol. Appl. Pharmacol., 180, 92, 2002. 

Davis, D.C., Potter, W.Z., Jollow, D.J. and Mitchell, J.R. (1974). Species differences in hepatic glutathione depletion, covalent hinding and hepatic necrosis after acetaminophen. Life Sci. 14 2099-2109. 

Numan IT, Hassan MQ, Stohs SJ. 1990b. Protective effects of antioxidants against endrin-induced lipid peroxidation, glutathione depletion, and lethality in rats. Arch Environ Contam Toxicol 19 302-306. 

Capranico, G., Babudri, N., and Casciarii, G., 1986, Lack of effect of glutathione depletion on cytotoxicity, mutagenicity and DNA damage produced by doxorubicin in cultured cells. Chem.-Biol. Interact. 57 189-201... 

Chellman, G.J., White, R.D., Norton, R.M., and Bus, J.S. Inhibition of the acute toxicity of methyl chloride in male B6C3F1 mice by glutathione depletion, Toxicol Appl. Pharmacol, 86(1) 93-104, 1986. 

Indeed, TCA (42) at a concentration of 10 Xg/mL, has been shown to elevate levels of ROS, as measured by flow cytometry. Consistent with earlier observations regarding structure-activity relationships, Me-TCA (44) showed 3-fold induction of ROS while dihydro-TCA (43) had no effect on the cellular levels of ROS.It is noteworthy that parthenolide (45), a sesquiterpene natural product structurally related to TCA, has previously been shown to increase the levels of ROS by glutathione depletion in hepatocellular carcinoma cell lines. In a separate study, parthenolide was able to inhibit DNA synthesis, cause cell cycle arrest, and induce apoptosis which are important mechanisms for controlling tumor growth. 

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

I. Mechanistic assays on ROS, glutathione depletion and calcein uptake. Toxicology In Vitro An International Journal Published in Association with BIBRA, 19, 505—516. 

Alvarez C, Blade C, Cartana J. 1993. 2"Adrenergic blockade prevents hyperglycemia and hepatic glutathione depletion in nickel-injected rats. Toxicol Appl Pharm 121 112-117. 

Drew R Miners JO (1984) The effects of buthionine sulphoximine (BSO) on glutathione depletion and xenobiotic biotransformation. Biochem Pharmacol. 33 2989-2994. 

Potter WZ, Thorgeirsson SS, JoIIow DJ, et al. Acetaminophen-induced hepatic necrosis. V. Correlation of hepatic necrosis, covalent binding and glutathione depletion in hamsters. Pharmacology 1974 12 (3) 129-143. 

Acrylonitrile is toxic at high dose in several organs, which is possibly related to its glutathione-depleting activity. This toxicity might lead to tmnour formation by an indirect mechanism, although no data to support this are evident from the available toxicity data, such as increased cell turnover or DNA labelling. 

Both acrylonitrile and cyanoethylene oxide can conjugate with glutathione, leading to detoxification of these reactive compounds. At high doses of acrylonitrile, as used in animal studies, glutathione in certain tissues may be depleted. Such glutathione depletion will probably not occur at low-level human exposure. 

Saillenfait, A.-M., Payan, J.-P, Langonnc, I., Bey don, D., Grandclaude, M.-C., Sabate, J.-P. de Ceaurriz, J. (1993b) Modulation of acrylonitrile-indueed embryotoxicity in vitro by glutathione depletion. Arch. Toxicol.. 61, 164-172... 

Csanady, G.A., Kreuzer, P.E., Baur, C. Filser, J.G. (1996) A physiological toxicokinetic model for 1,3-butadiene in rodents and man blood concentrations of 1,3-butadiene, its metabolically formed epoxides, and of haemoglobin adducts—relevance of glutathione depletion. Toxicology, 113, 300-305... 

Stenius, U., Warholm, M., Raimug, A., Walles, S., Lundberg, 1. Hogberg, J. (1989) The role of glutathione depletion and toxicity in hydroquinone-induced development of enzyme-altered foci. Carcinogenesis, 10, 593-599... 

Positive if glutathione depleted with diethyl maleate... 

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