Measurements of lipid peroxidation and α-tocopherol destruction in vitro and in vivo and their significance in connexion with the biological function of vitamin E

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.4.e518 ◽

1988 ◽

Vol 255 (4) ◽

pp. E518-E524 ◽

Cited By ~ 4

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.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.6.r2149 ◽

2000 ◽

Vol 279 (6) ◽

pp. R2149-R2155 ◽

Cited By ~ 40

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.

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Supplementation with vitamin E but not beta-carotene in vivo protects low density lipoprotein from lipid peroxidation in vitro. Effect of cigarette smoking.

Arteriosclerosis and Thrombosis A Journal of Vascular Biology ◽

10.1161/01.atv.12.5.554 ◽

1992 ◽

Vol 12 (5) ◽

pp. 554-562 ◽

Cited By ~ 231

Author(s):

H M Princen ◽

G van Poppel ◽

C Vogelezang ◽

R Buytenhek ◽

F J Kok

Keyword(s):

Lipid Peroxidation ◽

Vitamin E ◽

Cigarette Smoking ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Beta Carotene ◽

Low Density ◽

Vitro Effect

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Comparison of the effects of dietary vitamin E on in vivo and in vitro parameters of lipid peroxidation in the rabbit

Free Radical Biology and Medicine ◽

10.1016/0891-5849(95)00078-c ◽

1995 ◽

Vol 19 (5) ◽

pp. 617-626 ◽

Cited By ~ 17

Author(s):

Sheila A. Wiseman ◽

Marline A.P. Van Den Boom ◽

Nanneke J. De Fouw ◽

Marjolein Groot Wassink ◽

Jos A.F.Op Den Kamp ◽

...

Keyword(s):

Lipid Peroxidation ◽

Vitamin E ◽

Dietary Vitamin

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Vitamin E and hepatotoxic agents

British Journal Of Nutrition ◽

10.1079/bjn19690037 ◽

1969 ◽

Vol 23 (2) ◽

pp. 297-307 ◽

Cited By ~ 26

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.

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IN VITRO AND IN VIVO EFFECT OF VITAMIN E ON NORMAL HUMAN PLATELETS. AGGREGATION AND ARACHIDONIC ACID (AA) METABOLISM

10.1055/s-0038-1644624 ◽

1987 ◽

Author(s):

V Kockmann ◽

E Véricel ◽

M Croset ◽

M Lagarde

Keyword(s):

Lipid Peroxidation ◽

Fatty Acids ◽

Vitamin E ◽

Human Platelets ◽

Low Doses ◽

Normal Human ◽

Relative Deficiency ◽

Oxygenated Products

Oxygenated metabolism of AA through cyclooxygenase and lipoxygenase pathways involves peroxide species and vitamin E has been extensively studied as an agent that could reduce this lipid peroxidation. In the present study, effects of vitamin E has been investigated upon AA metabolism in normal human platelets with both in vivo and in vitro approaches. Using low doses of vitamin E either in vivo or in vitro, we have succeeded to almost double plasma and platelet a-tocopherol (determinated by HPLC). Despite such an enrichment platelet aggregation induced by agents involved in the AA cascade (collagen, arachidonate and U46619) was not affected. Similarly, the oxygenation of exogenous AA determined by HHT, HETE and TxB2 production was not modified. When the oxygenated products were measured after thrombin stimulation, some variations could be noted, although rarely significant. The tendency was a decrease after in vitro enrichment and an increase when enrichment occured in vivo. Basal oxygenated metabolism of AA in vivo was assessed by measuring 6-Keto-PGFla, 2,3-dinor-6-Keto-PGFla, TxB2 and 2,3-dinor-TxB2 in urine. All of them tended to increase after vitamin E intake, although not significantly. The oxygenation of eicosapentaenoic acid, which is markedly potentiated by AA through its hydroperoxide, 12 HPETE, was not altered after vitamin E treatment, confirming that vitamin E does not alter the specific peroxidation of polyunsaturated fatty acids in normal platelets. We conclude that vitamin E supplement does not affect the AA dependent aggregation neither the oxygenated metabolism of AA in normal human platelets. This does not exclude that it might be however useful in platelets that exhibit a relative deficiency in this vitamin (e.g. diabetes and aging) where it could slow down both AA peroxidation and aggregation.

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Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

Current Cancer Drug Targets ◽

10.2174/1568009617666170623104030 ◽

2018 ◽

Vol 18 (4) ◽

pp. 365-371 ◽

Cited By ~ 2

Author(s):

Denis V. Mishchenko ◽

Margarita E. Neganova ◽

Elena N. Klimanova ◽

Tatyana E. Sashenkova ◽

Sergey G. Klochkov ◽

...

Keyword(s):

Lipid Peroxidation ◽

Acute Toxicity ◽

Histone Deacetylases ◽

Hydroxamic Acids ◽

Water Soluble ◽

Male Rat ◽

Hybrid Male ◽

Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

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