ascorbic-acid and phorone
ascorbic-acid has been researched along with phorone* in 7 studies
Other Studies
7 other study(ies) available for ascorbic-acid and phorone
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The biosynthesis of ascorbate protects isolated rat hepatocytes from cumene hydroperoxide-mediated oxidative stress.
Most animals synthesize ascorbate. It is an essential enzymatic cofactor for the synthesis of a variety of biological molecules and also a powerful antioxidant. There is, however, little direct evidence supporting an antioxidant role for endogenously produced ascorbate. Recently, we demonstrated that incubation of rat hepatocytes with 1-bromoheptane or phorone simultaneously depleted glutathione (GSH) and triggered rapid ascorbate synthesis. The present study investigates the hypothesis that endogenous ascorbate synthesis can confer protection against oxidative stress. Rat and guinea pig hepatocytes were depleted of GSH with 1-bromoheptane and subsequently treated with the oxidative stressor cumene hydroperoxide (CHP) in the presence or absence of the ascorbate synthesis inhibitor sorbinil. In rat hepatocytes, ascorbate content increased linearly (from 15.1 to 35.8 nmol/10(6) cells) over a 105-min incubation. Prior depletion of GSH increased CHP-induced cellular reactive oxygen species (ROS) production, lipid peroxidation, and cell death in rat and guinea pig hepatocytes. Inhibiting ascorbate synthesis, however, further elevated ROS production (2-fold), lipid peroxidation (1.5-fold), and cell death (2-fold) in rat hepatocytes only. This is the first time that endogenous ascorbate synthesis has been shown to decrease cellular susceptibility to oxidative stress. Protection by endogenously produced ascorbate may therefore need to be addressed when extrapolating data to humans from experiments using rodents capable of synthesizing ascorbate. Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Glutathione; Guinea Pigs; Hepatocytes; Imidazolidines; Ketones; Lipid Peroxidation; Oxidative Stress; Rats; Reactive Oxygen Species | 2005 |
Glycogenolysis is directed towards ascorbate synthesis by glutathione conjugation.
Using isolated rat hepatocytes we have shown that glutathione (GSH) depletion by glutathione-S-transferase (GST)-catalyzed conjugation with 1-bromoheptane or phorone was accompanied by a significant elevation in ascorbate synthesis. Glycogenolysis was also stimulated without a significant rise in glucose synthesis. Furthermore, when glycogenolysis was stimulated in control hepatocytes by increasing intracellular cAMP levels (with glucagon or dibutyryl cAMP), cellular glucose levels, but not ascorbate levels, increased. These data suggest that GSH depletion can stimulate ascorbate synthesis independently of glucose synthesis and that hepatocytes can direct glycogenolysis towards ascorbate synthesis during GSH conjugation. Topics: Animals; Ascorbic Acid; Bucladesine; Cyclic AMP; Diamide; Dithiothreitol; Fructose; Glutathione; Glutathione Disulfide; Glycogen; Hepatocytes; Heptanes; Imidazoles; Imidazolidines; Ketones; Male; Rats; Rats, Sprague-Dawley; Uridine Diphosphate Glucose | 2004 |
Cerebral antioxidant status and free radical generation following glutathione depletion and subsequent recovery.
This study was aimed to evaluate the oxidative damage, production of reactive oxygen species and the status of antioxidative defenses following cerebral GSH depletion induced by two classical depletors, diethylmaleate (DEM, 3 mmol/kg, i.p.) and phorone (PHO, 4 mmol/kg, i.p.). The treatment decreased (40-43%) brain glutathione levels at 2 h, followed by a partial recovery at 24 h. Cerebral glutathione depletion by these agents increased the levels of superoxide anion and hydroxyl radical at both the time intervals; however, hydrogen peroxide was high at 24 h only. It also produced a dramatic increase in the protein carbonyls at 2 h but not at 24h, without any significant effect on lipid peroxidation and conjugated diene levels. These rats showed a significantly lowered superoxide dismutase activity both at 2 h and 24 h of exposure, as compared to controls. Glutathione depletion enhanced catalase activity markedly at 2 h, followed by some recovery at 24 h. While Se-independent glutathione peroxidase (GPx) and glutathione S-transferase activities were increased at both 2 and 24 h time intervals, Se-dependent GPx and glucose-6-phosphate dehydrogenase were induced at 2 h only. Glutathione depletion decreased ceruloplasmin and vitamin E levels significantly at 2 h. However, ascorbic acid remained unaffected. It may be concluded that an acute cerebral glutathione depletion generates higher levels of reactive oxygen species, which may be responsible for oxidative modification of proteins. Some of these changes appear to recover soon after an activation of a variety of cellular antioxidant defense mechanisms and glutathione restoration. It appears that central nervous system is highly vulnerable to oxidative damage following a moderate glutathione depletion that may result from certain diseases or xenobiotic exposures. Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Ceruloplasmin; Free Radicals; gamma-Glutamyltransferase; Glutathione; Hydrogen Peroxide; Hydroxides; In Vitro Techniques; Ketones; Male; Maleates; Rats; Rats, Inbred Strains; Reactive Oxygen Species; Superoxides; Thiobarbituric Acid Reactive Substances; Vitamin E | 2000 |
In vivo effects of ascorbate and glutathione on the uptake of chromium, formation of chromium(V), chromium-DNA binding and 8-hydroxy-2'-deoxyguanosine in liver and kidney of osteogenic disorder shionogi rats following treatment with chromium(VI).
Several previous in vitro studies have indicated that ascorbate and glutathione are the major reductants of Cr(VI) in cells. In order to evaluate the in vivo effects of ascorbate and glutathione on Cr(VI)-induced carcinogenesis, Cr uptake and the formation of Cr(V), Cr-DNA adducts and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured in the liver and kidney of Osteogenic Disorder Shionogi (ODS) rats that lack the ability to synthesize ascorbate. Despite a 10-fold difference in tissue ascorbate levels among different dietary ascorbate groups, the Cr(V) signal intensity, Cr uptake and total Cr-DNA binding were not affected in either organ. Treatment of ODS rats with Cr(VI) (10 mg/kg) had no substantial effect on the levels of ascorbate and glutathione in these tissues. The levels of Cr(V) and Cr-DNA binding were approximately 2-fold higher in the liver than in the kidney, although the levels of total Cr uptake were similar in both tissues. Cr uptake levels were significantly lower in the liver and kidney of ODS rats treated with high levels of ascorbate and a high dose of Cr(VI) (40 mg/kg), suggesting a detoxifying role played by plasma ascorbate. Similarly, modulation of glutathione levels by N-acetyl-L-cysteine, L-buthionine-S, R-sulfoximine or phorone in these animals by up to 2-fold had little or no consistent effect on Cr uptake, Cr-DNA binding, Cr(V) levels or 8-OH-dG formation in either organ. One possible explanation is that reduction of ascorbate and glutathione concentration to <10 and 50%, respectively, of normal in these two organs still provides threshold levels of these two reductants that are in excess of what is needed for significant reductive activation of Cr(VI). Alternatively, it is possible that ascorbate and glutathione do not play a major role in the formation of Cr(V), Cr-DNA binding or 8-OH-dG and that other cellular reductants, such as cysteine or other amino acids, might be more important reductants of Cr(VI) in vivo. Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Animals; Antimetabolites; Ascorbic Acid; Buthionine Sulfoximine; Chromium; Deoxyguanosine; DNA Adducts; Free Radical Scavengers; Glutathione; Ketones; Kidney; Liver; Oxidation-Reduction; Rats; Rats, Mutant Strains | 1999 |
Potential role of cerebral glutathione in the maintenance of blood-brain barrier integrity in rat.
Using the model of glutathione (GSH) depletion, possible role of GSH in the maintenance of blood-brain barrier (BBB) integrity was evaluated in rats. Administration (i.p.) of GSH depletors, diethyl maleate (DEM, 1-4 mmol/kg), phorone (2-3 mmol/kg) and 2-cyclohexene-1-one (CHX, 1 mmol/kg), to male adults was found to deplete brain and liver GSH and increase the BBB permeability to micromolecular tracers (sodium fluorescein and [14C]sucrose) in a dose-dependent manner at 2h. However, BBB permeability to macromolecular tracers such as horseradish peroxidase and Evan's blue remained unaltered. It was also shown that observed BBB permeability dysfunction was associated with brain GSH depletion. A lower magnitude of BBB increase in rat neonates, as compared to adults, indicated a possible bigger role of GSH in the BBB function of mature brain. The treatment with N-acetylcysteine, methionine and GSH provided a partial to full protection against DEM-induced brain (microvessel) GSH depletion and BBB dysfunction; however, the treatment with alpha-tocopherol, ascorbic acid and turmeric were not effective. Our studies showed that cerebral GSH plays an important role in maintaining the functional BBB integrity. Topics: Acetaminophen; Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Blood-Brain Barrier; Brain; Curcuma; Glutathione; Ketones; Liver; Male; Maleates; Plant Extracts; Rats; Rats, Inbred Strains; Vitamin E | 1999 |
Enzyme-dependent ascorbate recycling in human erythrocytes: role of thioredoxin reductase.
Human erythrocytes efficiently reduce dehydroascorbic acid (DHA) to ascorbate, which helps to maintain the ascorbate content of blood. Whereas erythrocyte DHA reduction is thought to occur primarily through a direct chemical reaction with GSH, this work addresses the role of enzyme-mediated DHA reduction by these cells. The ability of intact erythrocytes to recycle DHA to ascorbate, estimated as DHA-dependent ferricyanide reduction, was decreased in parallel with GSH depletion by glutathione-S-transferase substrates. In contrast, the sulfhydryl reagent phenylarsine oxide inhibited DHA reduction to a much greater extent than it decreased GSH in intact cells. DHA reduction in excess of that due to a direct chemical reaction with GSH was also observed in freshly prepared hemolysates. Hemolysates likewise showed NADPH-dependent reduction of DHA that appeared due to thioredoxin reductase, because this activity was inhibited 68% by 10 microM aurothioglucose, doubled by 5 microM E. coli thioredoxin, and had an apparent Km for DHA (1.5 mM) similar to that of purified thioredoxin reductase. Additionally, aurothioglucose-sensitive, NADPH-dependent DHA reductase activity was decreased 80% in hemolysates prepared from phenylarsine oxide-treated cells. GSH-dependent DHA reduction in hemolysates was more than 10-fold that of NADPH-dependent reduction. Nonetheless, the ability of phenylarsine oxide to decrease DHA reduction in intact cells with little effect on GSH suggests that enzymes, such as thioredoxin reductase, may contribute more to this activity than previously considered. Topics: Arsenicals; Ascorbic Acid; Aurothioglucose; Cell Membrane; Cell-Free System; Dehydroascorbic Acid; Dinitrochlorobenzene; Dose-Response Relationship, Drug; Enzymes; Erythrocytes; Ferricyanides; Glutathione; Glutathione Transferase; Hemolysis; Humans; Ketones; NADP; Thioredoxin-Disulfide Reductase; Vitamin E | 1998 |
Mitochondrial lipid peroxides and antioxidant enzymes in the liver following phorone-induced glutathione depletion.
The levels of lipid peroxidation product (malondialdehyde = MDA) and vitamin C and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in the liver and its mitochondrial fraction, in the rats 2 and 18 hr after the injection of phorone, a glutathione (GSH) depleting agent. GSH levels decreased in liver homogenate and its mitochondrial fraction after 2 hr of phorone treatment, but these values returned to normal levels at 18 hr. In GSH depleted conditions, hepatic vitamin C levels increased, GSH-Px and SOD activities remained unchanged in mitochondrial and post-mitochondrial fractions. These results indicate that GSH depletion per se does not influence lipid peroxidation and GSH-Px and SOD activities in the liver and the mitochondrial fraction. Topics: Animals; Ascorbic Acid; Glutathione; Glutathione Peroxidase; Ketones; Lipid Peroxides; Male; Mitochondria, Liver; Rats; Rats, Wistar; Superoxide Dismutase | 1997 |