The effect of vitamin E on the oxidation state of selenium in rat liver

1. (75)Se as Na(2) (75)SeO(3) was administered orally to rats under different nutritional conditions. 2. The selenium found in the liver subcellular organelle fractions was present in at least three oxidation states: acid-volatile selenium, assumed to be selenide, zinc-hydrochloric acid-reducible selenium, assumed to be selenite, and higher oxidation states of selenium and organic derivatives, called selenate for convenience. 3. The proportion of the total selenium present as selenide present as selenide is susceptible to oxidation in vitro, which can be prevented by the addition of antioxidants in vitro. 4. The proportion of selenide is also directly related to the vitamin E status of the rats, and treatment of vitamin E-deficient rats with vitamin E results in an increase in the proportion of selenide. 5. Freezing the liver in situ before preparation of the organelle fractions did not alter the susceptibility of the selenide proportion to dietary vitamin E, indicating that the observed effects occur in vivo and not as a result of oxidation post mortem. 6. Intravenous administration of Na(2) (75)SeO(3), to rats whose alimentary tract was partially sterilized by neomycin treatment, gave a similar result to that in paragraph 4, indicating that the reduction of selenite to selenide probably occurs in vivo, and that intestinal micro-organisms are not responsible. 7. Treatment of vitamin E-deficient rats with silver produced a fall in the total (75)Se content of the liver, an effect only partially reversed by vitamin E administration. The proportion of the total selenium present as selenide was also lowered by the treatments with silver, and vitamin E significantly reversed this trend in most cases. 8. These results are consistent with the hypothesis that the active form of Se may be selenide and that the selenide may form part of the active centre of an uncharacterized class of catalytically active non-haem-iron proteins that are protected from oxidation in vivo by vitamin E.     

Effect of dietary beta-carotene on the accumulation of beta-carotene and vitamin A in plasma and tissues of gilts

The absorption of beta-carotene in pigs is limited. Nevertheless beta-carotene might positively affect reproduction. In this study the absorption and tissue distribution of beta-carotene as well as its function as precursor of vitamin A was investigated in gilts that were fed according to one of three dietary treatments: VA (4000 IU vitamin A), VA + VA (4000 IU + 8300 IU) and VA + BC (4000 IU + 100 mg beta-carotene per kg diet) for 14 weeks. Only in the VA + BC group was beta-carotene detected in plasma (1-8 ng x mL(-1)), liver, adrenals and corpora lutea, indicating that pigs absorb intact beta-carotene at low rates. Liver levels of vitamin A were higher (P < 0.01) at comparable levels in the VA + VA and VA + BC group than in the VA group, indicating a conversion rate of beta-carotene to vitamin A of 40 to 1 on the basis of weight for beta-carotene at this level (100 mg x kg(-1)) in the diet. Higher levels of vitamin A in the uterus of the VA + BC group (P < 0.01) as well as the accumulation of beta-carotene in adrenals and corpora lutea might reflect some influence of beta-carotene on local vitamin A metabolism which might be of importance for reproductive performance in gilts.     

The effect of vitamin E on the intracellular distribution of the different oxidation states of selenium in rat liver

1. The liver intracellular distribution of (75)Se, (75)Se(2-) and (75)SeO(3) (2-) formed from orally administered Na(2) (75)SeO(3) was studied in rats given four different dietary treatments. 2. Subcellular fractionation was done by using sucrose density gradients in a B XIV zonal centrifuge rotor, and conditions were established so that separation of lysosomal, mitochondrial, smooth- and rough-surfaced endoplasmic reticulum, and soluble fractions was achieved. 3. Marker enzymes acid phosphatase, succinate-2 - p - iodophenyl - 3 - p -nitrophenyl - 5 - phenyltetrazolium reductase and glucose 6-phosphatase were used, together with electron microscopy, to establish the identity of the fractions. 4. The dietary treatments investigated were: (a) vitamin E-deficient diet for 3 months, re-fed with vitamin E during the terminal 5 days; (b) vitamin E-deficient diet; (c) adequate diet; (d) vitamin E- and selenium-deficient diet, re-fed with vitamin E during the terminal 5 days. 5. In adequately fed rats, selenide was particularly associated with the mitochondrial fractions; in vitamin E-deficient rats, little selenide was found and the buoyant density of the mitochondria was increased, whereas re-feeding with vitamin E showed a restoration of the normal pattern. In vitamin E- and selenium-deficient rats, re-fed with vitamin E, there was no tendency for selenide to be localized in the mitochondria. 6. In the microsomal regions of the gradients, adequately fed rats showed a concentration of selenide, particularly in the smooth endoplasmic reticulum fractions, and to a lesser extent in the rough endoplasmic reticulum fractions. This was not observed in vitamin E-deficient rats, and the normal pattern was restored on re-feeding with vitamin E, both in rats given the vitamin E-deficient diet and the vitamin E- and selenium-deficient diet. 7. Some selenide was also found in the soluble fractions, when vitamin E was present, and a substantial proportion of this selenide was found to pass through a dialysis membrane. 8. These results are taken to support our hypothesis that the active form of selenium may be selenide located in non-haem iron-containing proteins, and that the function of vitamin E may be to protect the selenide from oxidation.     

Effects of vitamin E and beta-carotene on sperm competitiveness

Sperm are particularly prone to oxidative damage because they generate reactive oxygen species (ROS), have a high polyunsaturated fat content and a reduced capacity to repair DNA damage. The dietary compounds vitamin E and beta-carotene are argued to have antioxidant properties that help to counter the damaging effects of excess ROS. Here in, we tested the post-copulatory consequences for male crickets (Teleogryllus oceanicus) of dietary intake of these two candidate antioxidants. During competitive fertilisation trials, vitamin E, but not beta-carotene, singularly enhanced sperm competitiveness. However, the diet combining a high vitamin E dose and beta-carotene produced males with the most competitive ejaculates, possibly due to the known ability of beta-carotene to recycle vitamin E. Our results provide support for the idea that these two common dietary compounds have interactive antioxidant properties in vivo, by affecting the outcomes of male reproductive success under competitive conditions.     

The influence of dietary selenium and vitamin E on glutathione peroxidase and glutathione in the rat

The effect of dietary selenium (Se) and vitamin E supplementation on tissue reduced glutathione (GSH) and glutathione peroxidase activity has been studied in the rat. Increasing Se intake by 0.4 ppm gave significantly higher enzyme levels in all tissues studied, an effect not influenced by vitamin E intake. Further increasing Se to 4 ppm gave higher enzyme levels in red blood cells only, while in liver was there was a significant decrease in enzyme activity probably reflecting Se hepatotoxicity. In the absence of Se supplements increasing dietary vitamin E to 100 mg/kg diet significantly increased enzyme activity but this effect was modified by simultaneous Se supplementation.Se intake had no effect on GSH levels. Rats on high vitamin E intake 500 mg/kg had a significantly higher tissue GSH level. Dietary Se had a sparing effect on vitamin E, rats supplemented with Se having significantly raised plasma vitamin E levels.These results confirm the role of selenium in glutathione peroxidase and also show that vitamin E influences the activity of the enzyme.     

The effect of vitamin E on lipid peroxidation in the copper-deficient rat

The present study was designed to determine whether the supplementation of vitamin E in the copper-deficient diet would ameliorate the severity of copper deficiency in fructose-fed rats. Lipid peroxidation was measured in the livers and hearts of rats fed a copper-deficient diet (0.6 microg Cu/g) containing 62% fructose with adequate vitamin E (0.1 g/kg diet) or supplemented with vitamin E (1.0 g/kg diet). Hepatic lipid peroxidation was significantly reduced by vitamin E supplementation compared with the unsupplemented adequate rats. In contrast, myocardial lipid peroxidation was unaffected by the level of vitamin E. Regardless of vitamin E supplementation, all copper-deficient rats exhibited severe signs of copper deficiency, and some of the vitamin E-supplemented rats died of this deficiency. These findings suggest that although vitamin E provided protection against peroxidation in the liver, it did not protect the animals against the severity of copper deficiency induced by fructose consumption.     

Influence of dietary vitamin E on prostaglandin biosynthesis in rat blood

A vitamin E (-tocopherol) deficient diet stimulated prostaglandin biosynthesis in coagulating rat blood. Prostaglandins were extracted from serum, purified and bioassayed. The identity of prostaglandin E₂ was confirmed by gas chromatography-mass spectrometry. Withholding vitamin E from the diet caused a marked increase in PGE₂ and a lesser increase in PGF₂ production in serum. In rats maintained on diets containing different concentrations of vitamin E, serum concentrations of PGE₂ and PGF₂ were inversely related to serum concentrations of -tocopherol. These data suggest that in vivo -tocopherol inhibits the endogenous conversion of arachidonic acid into PGE₂ and PGF₂. The possibility that -tocopherol may inhibit the formation of endoperoxide intermediates of PGE₂ and PGF₂ biosynthesis and subsequent induction of platelet aggregation is discussed.     

Effect of dietary vitamin E and Santoquin on regenerating rat liver

The influence of dietary vitamin E and Santoquin on lipid peroxidation and liver regeneration in partially-hepatectomized rats was studied. Rats were fed either a basal 10% tocopherol-stripped corn oil diet, the basal diet plus 40 mg dl-alpha-tocopheryl acetate/kg, or the basal diet plus 2 g Santoquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline)/kg. After 6 weeks, rats fed the antioxidant-deficient diet produced more of the lipid peroxidation product, pentane, than did the rats fed antioxidants. Partial hepatectomy was performed after six and one-half weeks or ten weeks of feeding the diets. At 3 and 6 days after surgery, pentane production was significantly elevated over pre-surgery levels in rats fed the antioxidant-deficient or vitamin E-supplemented diets, but not in rats fed the Santoquin-supplemented diet. Six days after surgery, there were fewer thiobarbituric acid reactants in regenerating liver of Santoquin-fed rats than of vitamin-E fed rats or antioxidant-deficient rats. There was no increase in the 6-day level of thiobarbituric acid reactants over the 3-day level in livers of rats fed Santoquin, while there was an increase in livers of the antioxidant-deficient and vitamin E-supplemented rats. Liver sulfhydryl levels were higher at 3 and 6 days post surgery in the Santoquin-fed rats than in the antioxidant-deficient or vitamin E-supplemented rats. Plasma gamma-glutamyl-transpeptidase activity was not different among the groups of rats. Between the third and sixth day following surgery, liver regeneration was significantly stimulated in Santoquin-fed, but not vitamin E-fed rats. After 11 days, a stimulatory, but not statistically significant, effect of vitamin E was found. Although DNA content of liver was higher at 6 days than at 3 days post surgery, it was not different among the dietary groups, indicating that cell proliferation rather than hypertrophy had occurred. Partial hepatectomy could have altered the ability of the liver to metabolize pentane, thus explaining part of the increased production of pentane. However, the results obtained support the interpretation that elevated levels of dietary antioxidants can be beneficial in terms of reduced lipid peroxidation and increased rates of liver regeneration following liver surgery.     

Influence of dietary vitamin E on prostaglandin biosynthesis in rat blood.

A vitamin E (alpha-tocopherol) deficient diet stimulated prostaglandin biosynthesis in coagulating rat blood. Prostaglandins were extracted from serum, purified and bioassayed. The identity of prostaglandin E2 was confirmed by gas chromatography-mass spectrometry. Withholding vitamin E from the diet caused a marked increase in PGE2 and a lesser increase in PGF2alpha production in serum. In rats maintained on diets containing different concentrations of vitamin E, serum concentrations of PGE2 and PGF2alpha were inversely related to serum concentrations of alpha-tocopherol. These data suggest that in vitro alpha-tocopherol inhibits the endogenous conversion of arachidonic acid into PGE2 and PGF2alpha. The possibility that alpha-tocopherol may inhibit the formation of endoperoxide intermediates of PGE2 and PGF2alpha biosynthesis and subsequent induction of platelet aggregation is discussed.     

Analysis of the variable effect of dietary vitamin E supplements on experimental atherosclerosis

Vitamin E inhibits processes thought to be important in the development of atherosclerosis but clinical trials to determine its effect on cardiovascular disease have given variable results, the majority being negative. The reasons for this are unclear. Animal trials can be better controlled and use more rigorous measures of lesion progression than human trials. The present study reviewed trials using rabbits and mice to determine whether they also are variable and, if so, to uncover methodological differences that may account for the different outcomes. A large number of trials examining the effect of vitamin E supplements on experimental atherosclerosis were identified. Using rigorous selection criteria, a well-defined group was selected for further investigation. Almost all the mice trials showed a significant effect of vitamin E, but only around one-third of the rabbit trials did so. When the rabbit trials were divided into those that did and those that did not observe significant effects, no single factor was found that could account for the dichotomy. However, when the percentage reduction in disease was considered, rather than the within-trial significance level, there were clear dose-dependent effects of vitamin E on disease severity in heritable hyperlipidaemic rabbits, and in genetically normal rabbits made hyperlipidaemic with cholesterol alone; the dose dependence was different in the two groups, the heritable hyperlipidaemic rabbits showing a near ten-fold lower sensitivity. The high doses required to affect experimental atherosclerosis may, if applicable to other species, help explain the absence of effects in many human trials.     

The effect of selenium and vitamin E on microvascular permeability of rat organs

The effects of dietary sodium selenite and vitamin E on the microvascular permeability of rat organs such as heart, brain, kidney, liver and eye were investigated by using the Evans blue leakage method. Combined deficiency of selenium and vitamin E caused an increase in the permeability of the heart and eye with respect to their controls while it had no considerable effect on the permeability of other organs. On the other hand, toxic levels of selenium (4.2 mg/kg) in diet decreased the permeabilities in kidney, liver, and eye whereas this parameter of brain increased in the same animal group. These results suggested that low or high sodium selenite and vitamin E contents in diet could alter the microvascular permeability of different organs in different manners. It might be important to give reasonable explanations for the pathophysiology of some diseases that are characterized with organ damage and /or disfunction originated from selenium deficiency or toxicity.     

Dual effect of glucose on LDL oxidation: dependence on vitamin E

The aim of the present study was to determine the direct effect of glucose on LDL oxidation, a key step in the development of atherosclerosis. Purified human LDL were incubated with glucose (500 mg/dl) and LDL oxidation was started by adding CuCl(2) to the media. Glucose delayed the vitamin E consumption, but accelerated the formation of conjugated dienes and increased both the formation of thiobarbituric acid reacting substances (TBARS) and LDL electrophoretic mobility. When LDL were incubated with increasing concentrations of glucose and submitted to oxidation, the formation of conjugated dienes, TBARS, and the electrophoretic mobility increased in a concentration-dependent manner. When LDL was enriched with vitamin E, it showed a delay in the formation of conjugated dienes, even in the presence of glucose. To determine whether glucose had any effect on LDL oxidation, once the process was started and vitamin E consumed, LDL were submitted to oxidation and, at different times thereafter, glucose was added into the media. Under these conditions glucose also accelerated the LDL oxidation. In summary, present results show that in LDL submitted to oxidation, glucose delays the early phases of the oxidation, slowing the vitamin E consumption, but it accelerates the rate of LDL oxidation once LDL vitamin E has been consumed; the effect being concentration-dependent.