scholarly journals Vitamin E and hepatotoxic agents

1969 ◽  
Vol 23 (2) ◽  
pp. 297-307 ◽  
Author(s):  
J. Green ◽  
J. Bunyan ◽  
M. A. Cawthorne ◽  
A. T. Diplock
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Rat Liver ◽  
Protective Action ◽  
Lipid Peroxides ◽  
Ultraviolet Region ◽  
Intraperitoneal Dose ◽  
And Control

1. It has been suggested that carbon tetrachloride damages rat liver by accelerating processes of lipid peroxidation at subcellular sites and that the protective action of vitamin E is due to its functioning as an antioxidant in vivo. Direct evidence for these mechanisms in vivo has been sought and is critically examined.2. The increased production of malondialdehyde by rat liver microsomal fractions during incubation with CCl4 was shown to be a function of the vitamin E status of the rat and of an in vitro reaction, which could not be correlated with the hepatotoxic action of CCI4.3. Evidence for the production of lipid peroxides by CCl4 in the livers of vitamin E-deficient and vitamin E-supplemented rats was sought (I) by measurement of ultraviolet spectral changes ('diene' formation) and (2) by direct micro-iodimetric determination of the peroxide. No differences in peroxide content were found between CC14-treated and control rats, nor were the spectrophotometric changes in the ultraviolet region related to the presence of vitamin E.4. The effect of CCI4 (2.0 ml/kg orally) on ATP levels in rat liver was studied at intervals from 3 to 68 h. The primary lesion leading to necrosis and fat accumulation after CCl4 treatment occurred many hours before the eventual slight decline in ATP. Although the levels of ATP were somewhat higher in vitamin E-deficient rats, vitamin E did not prevent the slight decline in ATP that took place. Since ATP is known to be highly sensitive to peroxidation, the results suggest that lipid peroxidation is not the primary event in CCl4 poisoning.5. The effect of CC14on the metabolism of [14C]D-α-tocopherol in the rat was studied. A single intraperitoneal dose of CCl4 (2.0 m/kg) did not increase the destruction of α-tocopherol in the liver or carcass after 24 h. Three smaller daily doses of CC14 (0.25 ml/kg) also did not increase α-tocopherol catabolism; on the contrary, significantly more α-tocopherol was found in the livers of rats treated with CCI4. These results suggest that CCl4 does not increase lipid peroxidation in vivo.

DNA stability and lipid peroxidation in vitamin E–deficient rats in vivo and colon cells in vitro

2004 ◽  
Vol 44 (4) ◽  
pp. 195-203 ◽  
Author(s):  
S. J. Duthie ◽  
P. T. Gardner ◽  
P. C. Morrice ◽  
S. G. Wood ◽  
L. Pirie ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Dna Stability ◽  
Colon Cells

scholarly journals Brain Lipid Peroxidation Induced by Postischemic Reoxygenation in vitro: Effect of Vitamin E

1984 ◽  
Vol 4 (3) ◽  
pp. 466-469 ◽  
Author(s):  
Shinichi Yoshida ◽  
Raul Busto ◽  
Mercedes Santiso ◽  
Myron D. Ginsberg
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Lipid Peroxides ◽  
Aerobic Incubation ◽  
Ischemic Hypoxia ◽  
Brain Lipid Peroxidation ◽  
Vitro Effect ◽  
The Brain ◽  
Slow Propagation

The aerobic incubation of brain afer a period of ischemia induced lipid peroxidation. The effect was greatest in vitamin E—deficient rats, intermediate in vitamin E—normal rats, and least in animals supplemented with vitamin E. In contrast, nitrogen incubation following ischemia produced a small effect only in the vitamin E—deficient animals. It appears that reoxygenation is required for lipid peroxides to accumulate in the brain. However, a trace of oxygen remaining during extreme ischemic hypoxia may be sufficient to cause slow propagation of free radical reactions when the vitamin E level is low.

scholarly journals Vitamin E and stress

1967 ◽  
Vol 21 (3) ◽  
pp. 671-679 ◽  
Author(s):  
M. A. Cawthorne ◽  
A. T. Diplock ◽  
I. R. Muthy ◽  
J. Bunyan ◽  
Elspeth A. Murrell ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Vitamin E ◽  
Lipid Peroxide ◽  
Toxic Effects ◽  
Peroxide Content ◽  
In Vitro Techniques ◽  
Sulphydryl Compounds

1. Vitamin E-deficient rats were found to be more susceptible than vitamin E-supplemented controls to the toxic effects of hyperbaric oxygen (60 lb/in.2 for 20 min). This agrees with the findings of other workers.2. Hyperbaric O2 treatment did not increase the metabolic destruction of a small amount (46.65 μg) of [14C-5-Me]D-α-tocopherol given to adult vitamin E-deficient rats 24 h previously. The O2 treatment also did not affect the soluble sulphydryl compounds and ascorbic acid of rat liver, nor the percentag haemolysis in vivo of rat blood.3. Hyperbaric O2 treatment did not increase the true lipid peroxide content of rat brain, compared to control rats treated with hyperbaric air, which has no toxic effects. Increases in ‘lipid peroxidation’ reported by previous workers are considered to have been due to the use of inadequate controls (untreated rats) and of in vitro techniques that are open to criticism.4. The toxic effects of hyperbaric O2 in the vitamin E-deficient rat cannot be attributed to peroxidation in vivo.5. Vitamin E was not found to protect rats against the effects of reduced O2 tension (anoxic anoxia). This finding contrasts with some reports by earlier workers. Reduced O2 tension had no effect on the metabolism of radioactive tocopherol, on blood haemolysis in vivo, or on the soluble sulphydryl compounds and ascorbic acid of liver.

Inhibition by saccharin of glucose-6-phosphatase: effects of alloxan in vivo and deoxycholate in vitro

1976 ◽  
Vol 54 (6) ◽  
pp. 587-590 ◽  
Author(s):  
David G. Lygre
Keyword(s):  
Kinetic Parameters ◽  
Rat Liver ◽  
Control Groups ◽  
Major Significance ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
And Control

Inhibition by saccharin of rat liver glucose-6-phosphatase (EC 3.1.3.9) generally decreased as the pH increased in the range pH 4–8. This pattern was exhibited by homogenates from control and alloxan-treated animals assayed each in the absence and presence of 0.2% (w/v) deoxycholate. Saccharin inhibited in competitive fashion with respect to glucose-6-phosphate (glucose-6-P). There was a small increase in Km (glucose-6-P) but not Ki (saccharin) values in alloxan-treated rats when assays were conducted in the absence of deoxycholate. In the presence of this detergent there was no significant difference in these kinetic parameters between the alloxan-treated and control groups. Deoxycholate decreased Km (glucose-6-P) and increased Ki (saccharin) values. Calculations using these kinetic parameters indicate that, under usual hepatic glucose-6-P concentrations and relatively high levels of saccharin in liver, the inhibition by saccharin of glucose-6-phosphatase is unlikely to be of major significance in vivo.

Metallothionein response to stress in rats: role in free radical scavenging

1988 ◽  
Vol 255 (4) ◽  
pp. E518-E524 ◽  
Author(s):  
J. Hidalgo ◽  
L. Campmany ◽  
M. Borras ◽  
J. S. Garvey ◽  
A. Armario
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Liver Lipid ◽  
Radical Scavenging ◽  
Antioxidant Vitamin ◽  
Response To Stress ◽  
Liver Lipid Peroxidation

The possibility that liver metallothionein (MT) can function as an antioxidant in vivo has been studied in the rat. It was found that the stress of food and water deprivation with or without physical immobilization consistently increased liver lipid peroxidation (LLP), suggesting that liver MT induction by stress might be related to the stress-induced LLP. This was supported by results with the lipid peroxidation promoter dimethyl sulfoxide (DMSO) and the natural antioxidant vitamin E. Whereas DMSO administration increased LLP levels in basal and stress situations, vitamin E decreased them. Liver MT levels were increased by DMSO in basal and stress situations, whereas they were decreased by vitamin E during stress. These in vivo results are consistent with an antioxidant role of liver MT suggested by previous in vitro results. However, liver MT preinduction by Zn treatment did not result in a lower MT response to stress. Instead a positive synergistic effect between Zn and stress appeared to be present. This result indicates that the mechanism of action of MT as antioxidant remains unclear.

Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and α-lipoic acid

2000 ◽  
Vol 279 (6) ◽  
pp. R2149-R2155 ◽  
Author(s):  
Jeff S. Coombes ◽  
Scott K. Powers ◽  
Karyn L. Hamilton ◽  
Haydar A. Demirel ◽  
R. Andrew Shanely ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Myocardial Ischemia ◽  
Lipoic Acid ◽  
Ischemia Reperfusion ◽  
Control Diet ◽  
Cardiac Performance ◽  
Aged Rats

The purpose of these experiments was to examine the effects of dietary antioxidant supplementation with vitamin E (VE) and α-lipoic acid (α-LA) on biochemical and physiological responses to in vivo myocardial ischemia-reperfusion (I-R) in aged rats. Male Fischer-334 rats (18 mo old) were assigned to either 1) a control diet (CON) or 2) a VE and α-LA supplemented diet (ANTIOX). After a 14-wk feeding period, animals in each group underwent an in vivo I-R protocol (25 min of myocardial ischemia and 15 min of reperfusion). During reperfusion, peak arterial pressure was significantly higher ( P < 0.05) in ANTIOX animals compared with CON diet animals. I-R resulted in a significant increase ( P < 0.05) in myocardial lipid peroxidation in CON diet animals but not in ANTIOX animals. Compared with ANTIOX animals, heart homogenates from CON animals experienced significantly less ( P < 0.05) oxidative damage when exposed to five different in vitro radical producing systems. These data indicate that dietary supplementation with VE and α-LA protects the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species. Importantly, this protection is associated with improved cardiac performance during reperfusion.

scholarly journals The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used

1971 ◽  
Vol 123 (5) ◽  
pp. 805-814 ◽  
Author(s):  
T. F. Slater ◽  
B. C. Sawyer
Keyword(s):  
Lipid Peroxidation ◽  
Endoplasmic Reticulum ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Lipid Peroxides ◽  
Square Root ◽  
Microsomal Membranes ◽  
Stimulation Of ◽  
Homolytic Dissociation

1. The general features of the reaction by which carbon tetrachloride stimulates lipid peroxidation have been elucidated in rat liver microsomal suspensions and in mixtures of microsomes plus cell sap. The production of lipid peroxides has been correlated with malonaldehyde production in the systems used. 2. The stimulation of malonaldehyde production by carbon tetrachloride requires a source of reduced NADP+ and is dependent on the extent of the endogenous peroxidation of the microsomal membranes: if extensive endogenous peroxidation occurs during incubation then no stimulation by carbon tetrachloride is apparent. 3. The stimulation of malonaldehyde production by carbon tetrachloride has been shown to be proportional to the square root of the carbon tetrachloride concentration in the incubation mixture. It is concluded that the stimulation of malonaldehyde production by carbon tetrachloride results from an initiation process that is itself dependent on the homolytic dissociation of carbon tetrachloride to free-radical products. 4. The increased production of malonaldehyde due to carbon tetrachloride is accompanied by a decreased activity of glucose 6-phosphatase in rat liver microsomal suspensions. 5. The relative activities of bromotrichloromethane, fluorotrichloromethane and chloroform have been evaluated in comparison with the effects of carbon tetrachloride in increasing malonaldehyde production and in decreasing glucose 6-phosphatase activity. Bromotrichloromethane was more effective, and fluorotrichloromethane and chloroform were less effective, than carbon tetrachloride in producing these two effects. It is concluded that homolytic bond fission of the halogenomethanes is a requisite for the occurrence of the two effects observed in the endoplasmic reticulum.

scholarly journals The inhibitory effects in vitro of phenothiazines and other drugs on lipid-peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride

1968 ◽  
Vol 106 (1) ◽  
pp. 155-160 ◽  
Author(s):  
T F Slater
Keyword(s):  
Lipid Peroxidation ◽  
Carbon Tetrachloride ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Protective Agent ◽  
Liver Necrosis ◽  
Inhibitory Effects

1. The effects of several phenothiazine derivatives on lipid-peroxidation systems in rat liver microsomes were studied and the results are considered in relation to the hepatotoxic action of carbon tetrachloride. 2. The lipid-peroxidation system coupled to NADPH2 oxidation and stimulated by an ADP–Fe2+ mixture is strongly inhibited in vitro by promethazine (50% inhibition at 29μm). Chlorpromazine and Stelazine also inhibit the peroxidation system but are less effective than promethazine. 3. The effects of promethazine on three other systems involving oxygen uptake (sulphite oxidation, orcinol oxidation and mitochondrial succinate oxidation) were also studied. Promethazine does not inhibit these systems to the same extent as it does the NADPH2–ADP–Fe2+ lipid-peroxidation system. 4. Promethazine also produces an inhibition of the NADPH2–ADP–Fe2+ system in liver microsomes after administration in vivo. It is concluded that the inhibition involves the interaction of the drug (or a metabolite of it) with the microsomal electron-transport chain. 5. Several other compounds known to protect the rat against liver necrosis after the administration of carbon tetrachloride were tested for inhibitory action on the NADPH2–ADP–Fe2+ system. No clear correlation was observed between effectiveness in vivo as a protective agent and inhibitory effects on the NADPH2–ADP–Fe2+ system in vitro. 6. Promethazine was found to inhibit the stimulation of lipid peroxidation produced in rat liver microsomes by low concentrations of carbon tetrachloride. This effect occurs at a concentration similar to that observed in vivo after administration of a normal clinical dose.

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