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Novel aspects of vitamin A metabolism in the dog: distribution of lipoprotein retinyl esters in vitamin A-deprived and cholesterol-fed animals.

Retinyl ester concentrations in plasma from fasting humans, rabbits and rats are usually negligible. In contrast, plasma from fasting dogs contains appreciable amounts of retinyl esters, associated almost entirely with the low-density lipoproteins. This study was undertaken to gather additional information about the nature and origin of canine retinyl ester-containing lipoproteins. We examined the metabolism of endogenous lipoprotein retinyl esters in adult mongrel dogs with moderate vitamin A deficiency. Four animals were fed a diet of oatmeal and tuna fish that provided only 4% of the vitamin A contained in their control rations (15 vs. 367% of the canine recommended daily intake). There was an initial rapid decline in plasma retinyl esters. However, measurable concentrations persisted in plasma for up to 1 year of restricted vitamin A intake. Total plasma retinyl ester concentrations after 6 months of vitamin A deprivation, extrapolated from best-fit monoexponential decay curves for each animal, ranged from 11 to 89% of control, suggesting that there was sustained secretion of retinyl esters from endogenous stores. Density gradient ultracentrifugation of plasma from fasting vitamin A-deprived dogs showed retinyl esters in the very-low- and low-density lipoproteins. After fat and vitamin A feeding retinyl esters appeared among the very-low-, intermediate- and low-density lipoproteins, consistent with the suggestion that chylomicron retinyl esters are first taken up by the liver, and then resecreted as density less than 1.006-1.063 g/ml lipoproteins. Maximal incorporation of dietary retinyl esters into low-density lipoproteins was not reached until 24-48 h. Intermediate-density and beta-migrating low-density lipoprotein retinyl esters were increased markedly in fasting animals maintained on cholesterol- and saturated fat-enriched diets. These observations provide further evidence for the proposal that the canine liver secretes retinyl ester-containing particles, in amounts governed by dietary composition and vitamin A content. What selective advantage this unusual transport pathway might provide is not apparent.

Animals↗

Preparation of vitamin B-12-free serum for the use in vitamin B-12 radioassays.

In radioassays for serum vitamin B-12, the separation of free and bound vitamin is usually made with charcoal absorption. The specificity of this separation depends on the amount of charcoal and the protein content and constitution of the medium. The large difference in protein concentration between the samples for the dilution curve and the serum samples introduces an uncontrolled variable in the test. In order to equalize the experimental circumstances, the standard dilutions were made in serum freed from vitamin B-12 after boiling the serum for 20 min in a 4-fold dilution with glutamic acid buffer at pH 3.3 and subsequent passage over a CH-Sepharose 4-B column complexed with hog intrinsic factor (IF). The vitamin B-12-binding capacity of such an affinity column prepared from 1 g CH-Sepharose and 20 mg IF, suffices for the absorption of vitamin B-12 in 3000 ml serum from which 300 series of vitamin B-12 standard solutions can be made. Our first results with this method confirm that the charcoal absorption radioassay has become more accurate by the use of vitamin B-12-free serum in the standard dilutions.

Charcoal↗

Effect of vitamin D3 administration on serum 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and osteocalcin in vitamin D-deficient elderly people.

In elderly institutionalized people, confined to bedroom and receiving no vitamin D supplementation, the frequency of vitamin D deficiency is found very high. Systematic administration of vitamin D has, therefore, been proposed to correct vitamin D deficiency. Within this context, we studied 40 elderly institutionalized subjects (mean age 80.5 + 7.2 yr) with low 25(OH)D3 concentrations (4.4 + 1.8 micrograms/l). Sixteen of them (Group I) had low serum calcium concentrations (less than 2.3 mmol/l) and 24 (Group II) had normal serum calcium concentrations (from 2.3 to 2.6 mmol/l). As hypocalcemia has been shown to regulate 1,25(OH)D3 production independent of PTH in animals and in humans, we compared their respective responses to the administration of vitamin D3. Subjects received a total dose of 15 mg (600,000 IU) of vitamin D3 divided into 3 i.m. injections at one month intervals and were explored before therapy and one and 6 months after the last dose of vitamin D3. The treatment induced a similar marked rise in 25(OH)D3 levels (from 4.1 + 1.7 to 24.4 + 8.7 micrograms/l for group I and from 5.1 + 1.8 to 27.2 + 8.0 micrograms/l for group II) in both groups but increased the 1,25(OH)2D3 concentrations only in group I (from 22.9 + 6.9 to 32.6 + 11.3 ng/l). Meanwhile serum calcium concentrations rose in group I (to low normal range i.e. 2.31 + 0.07 mmol/l) and were unaffected in group II. These results suggest that hypocalcemia is a potent stimulator of renal 1-hydroxylase in elderly people. Furthermore, a transient significant (P less than 0.01) increase in serum osteocalcin (from 10.6 + 4.1 to 14.1 + 5.9 micrograms/l) could be observed in group I which demonstrates for the first time that the osteocalcin response of osteoblasts to stimulation by 1,25(OH)2D3 is retained in very old people.

Aged↗

Radioprotection by vitamin E: injectable vitamin E administered alone or with WR-3689 enhances survival of irradiated mice.

Radioprotection by injectable vitamin E (alpha-tocopherol) was investigated in mice exposed to 60Co radiation (0.2 Gy/min). Vitamin E injected subcutaneously either 1 hr before or within 15 min after irradiation significantly increased 30-day postirradiation survival in CD2F1 male mice. A dose reduction factor (DRF) of 1.11 (95% confidence interval [1.08, 1.14]) was observed for vitamin E at a dose of 100 IU/kg body weight administered within 15 min after irradiation. Combination studies with the phosphorothioate WR-3689 (S-2([3-methylaminopropyl]amino)ethylphosphorothioic acid) were undertaken to determine whether radioprotection by WR-3689 could be enhanced by vitamin E. Mice were given WR-3689 (150-225 mg/kg, intraperitoneally) 30 min before irradiation and were given vitamin E (100 IU/kg) either 1 hr before or within 15 min after irradiation. Survival was significantly increased in mice given vitamin E and WR-3689 before irradiation as compared to mice given WR-3689 alone: the DRF for WR-3689 (150 mg) was 1.35 [1.32, 1.38]; for WR-3689 combined with vitamin E (100 IU), the DRF was 1.49 [1.45, 1.53].

Amifostine↗

Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator function in postmenopausal women with established coronary artery disease: a substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial.

We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.

Aged↗

The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor.

INTRODUCTION: Few studies have considered the dietary influence of vitamin D intake on bone mineral density (BMD). Numerous studies have examined the association between VDR polymorphism and BMD, but no previous study has examined the joint influence of dietary vitamin D intake and VDR polymorphism on BMD. METHODS: We therefore conducted a study in 230 men aged 41-76 years of age. BMD was measured with DXA. A second bone scan was performed on average 2.7 years after the first investigation. Dietary habits were assessed by 14 dietary 24-h recall interviews. The polyadenosine (A) VDR genotypes were determined. RESULTS: Dietary vitamin D intake was associated with BMD at all sites, also after multivariate adjustment. Those in the highest quintile of intake had 9% higher femoral neck BMD (p = 0.004), 6% higher BMD at the lumbar spine (p = 0.06) and 5% higher total body BMD (p = 0.003) compared to men in the lowest quintile of dietary vitamin D intake. However, the positive association between vitamin D intake and BMD was especially apparent among those with the L/L polyadenosine (A) VDR genotype explaining between 10 and 15% of the variability in BMD depending on site (p < 0.004). There was furthermore a trend, in the lumbar spine, of less reduction in BMD with increasing vitamin D intake (p = 0.07) but not at the other sites. Calcium intake conferred no association with BMD. CONCLUSIONS: Our results indicate that the extent of positive association between dietary vitamin D intake and BMD in men is dependent on VDR polymorphism, a novel conceivable important gene-environmental interaction.

Adenosine↗

Effect of a nutritional supplement containing vitamin E, selenium, vitamin c and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate: a randomised placebo-controlled study.

OBJECTIVE: To assess the effect of a nutritional supplement containing vitamin E, selenium, vitamin C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated carcinoma of the prostate and rising serum PSA levels. METHODS: Eighty patients were randomised to receive a daily supplement with either vitamin E, selenium, vitamin C, coenzyme Q10 (intervention group) or placebo over 21 weeks. Serum levels of PSA were assessed at baseline (-2, -1, 0 weeks) and after 6, 13, 19, 20 and 21 weeks. Mean changes in log serum level of PSA, testosterone, dihydrotestosterone, luteinizing hormone and sex hormone binding globulin over 21 weeks between the verum and the placebo group were compared by analysis of covariance. RESULTS: Seventy patients completed the study (36 verum; 34 placebo). Compliance was >90% in all patients. In the intervention group, plasma levels of vitamin E, selenium and coenzyme Q10 increased significantly over the 21 weeks study period. No significant differences in serum levels of PSA, testosterone, dihydrotestosterone, luteinizing hormone or sex hormone binding globulin (p>0.2) were observed between the intervention and control group. CONCLUSION: Our results indicate that supplementation of a combination of vitamin E, selenium, vitamin C and coenzyme-Q10 does not affect serum level of PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate.

Aged↗

Vitamin C and vitamin E supplementation reduce oxidative stress-induced embryo toxicity and improve the blastocyst development rate.

To evaluate the adverse effects of exogenously induced reactive oxygen species (ROS) on mouse embryo development by using the 12-phorbol 13-myristate acetate (PMA)-activated leukocyte model as a source of ROS, and to examine the protective effect of antioxidant supplementation (vitamin C and vitamin E). Prospective study. Research laboratory. Effects of ROS on the blastocyst development rate in the presence and absence of antioxidant supplementation. After incubation with the PMA-activated leukocyte supernatant, the median (25th, 75th percentile) rate of blastocyst development significantly decreased from 73% (60%, 80%) after 3 hours to 30% (20%, 40%) after 6 hours compared with control reactions (86% [80%, 100%]). Co-incubating the embryos with vitamin C (50 microM) and the PMA-activated supernatant significantly increased the blastocyst development rate from 73% (60%, 80%) to 90% (80%, 91%) at 3 hours and from 30% (20%, 40%) to 91% (89%, 91%) at 6 hours-a level similar to that of control reactions. The blastocyst development rate increased after vitamin E supplementation (400 microM) at 6 hours, but not significantly and not by as much as after vitamin C supplementation. Exposure of mouse embryos to ROS for extended periods results in embryotoxicity. Vitamin C is more effective than vitamin E in reversing ROS-induced mouse embryo toxicity.

Animals↗

Comparison of vitamin D and 25-hydroxy-vitamin-D in the therapy of primary biliary cirrhosis.

Skeletal demineralisation and low serum concentrations of 25-hydroxy-vitamin-D were observed in patients with primary biliary cirrhosis. Neither oral nor parenteral vitamin-D increased 25-hydroxy-vitamin-D in serum or prevented further skeletal demineralisation. In contrast, oral 25-hydroxy-vitamin-D increased serum-25-hydroxy-vitamin D concentrations in all patients, and bone mineral content either improved or stabilised in all but one, 25-hydroxy-vitamin-D may be the preferred form of vitamin-D therapy in primary biliary cirrhosis.

Administration, Oral↗

Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes.

Vitamin E, an antioxidant, improves insulin sensitivity through the suppression of conventional PKC in vascular smooth muscle cells. It has been reported that vitamin E reduces platelet aggregation through the suppression of PKC alpha and beta (Diabetes 47 (1998) 1494). On the other hand, 1 alpha,25-dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may subsequently cause insulin resistance. Against this background, we examined the effect of vitamin E and 1,25D3 on PKC beta and PKC zeta/lambda activities in vitro and 10 nM insulin-induced glucose uptake in rat adipocytes. In vitro PKC beta activity of adipocytes was slightly decreased by the addition of 1 microM vitamin E, but not PKC zeta/lambda activity. In contrast, a 10-1000 nM 1,25D3 dose responsively activated PKC beta activity of adipocytes (ED 50%, 10 nM), but not PKC zeta/lambda activity. Pretreatment with 1 microM vitamin E for 60 min did not improve the insulin-induced glucose uptake. On the other hand, pretreatment with a 10-1000 nM 1,25D3 dose responsively suppressed insulin-induced glucose uptake. Moreover, 1,25D3 increased membrane-associated PKC beta immunoreactivity for 60 min, but no additional increase in membrane-associated PKC beta immunoreactivity during treatment with insulin was observed. These results suggest that 1,25D3 reduces insulin-induced glucose uptake via activation of PKC beta, but not vitamin E in rat adipocytes.

Adipocytes↗

Skin tumor promotion by Vitamin E in mice: amplification by ionizing radiation and Vitamin C.

We have shown previously that Vitamin E acts as a tumor promoter in 7,12-dimethylbenz(a)anthracene (DMBA) initiated mouse skin. We now show that high concentrations (80 micromol) of Vitamin E are required for promotion, and that 10-fold lower concentrations do not promote tumor formation. The same high concentration of the water-soluble anti-oxidant Vitamin C did not act as a tumor promoter, but did amplify the promoting effect of high, but not low, concentrations of Vitamin E. Oxidizing free radicals generated by beta-radiation exposure of the skin at the time of Vitamin E treatment also enhanced promotion by high (but not low) concentrations of Vitamin E. The results are consistent with a process whereby tumor promotion by the lipid-soluble Vitamin E occurs as a result of alpha-tocopherol acting as a free radical scavenger, with the formation and subsequent transfer of the alpha-tocopherol free radical center to the surrounding lipids, resulting in lipid oxidations.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women.

OBJECTIVES: To investigate the therapeutic effect of combined use of vitamin K(2) and D(3) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis. SUBJECTS AND METHODS: We enrolled 172 women with vertebral bone mineral density <0.98 g/cm(2) (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K(2) therapy group, vitamin D(3) therapy group, vitamin K(2) and D(3) combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen. RESULTS: Combined therapy with vitamin K(2) and D(3) for 24 months markedly increased bone mineral density (4.92 +/- 7.89%), while vitamin K(2) alone increased it only 0.135 +/- 5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis-coagulation system. CONCLUSIONS: Continuous combination therapy with vitamin K(2) and D(3) may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.

Absorptiometry, Photon↗

Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis.

We studied the effect of vitamin C, vitamin E, and beta carotene intake on the risk of Parkinson's disease (PD). We did a systematic review and meta-analysis of observational studies published between 1966 and March 2005 searching MEDLINE, EMBASE, and the Cochrane Library. Eight studies were identified (six case-control, one cohort, and one cross-sectional). We found that dietary intake of vitamin E protects against PD. This protective influence was seen with both moderate intake (relative risk 0.81, 95% CI 0.67-0.98) and high intake (0.78, 0.57-1.06) of vitamin E, although the possible benefit associated with high intake of vitamin E was not significant. The studies did not suggest any protective effects associated with vitamin C or beta carotene. We conclude that dietary vitamin E may have a neuroprotective effect attenuating the risk of PD. These results require confirmation in randomised controlled trials.

Ascorbic Acid↗

A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH). We conducted a pilot study for the following reasons: (1) to test the hypothesis that a combination of an antioxidant (vitamin E) and an insulin sensitizer (pioglitazone) would be superior to vitamin E alone for the treatment of NASH, and (2) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology. METHODS: A randomized prospective trial was performed to compare the efficacy and safety of vitamin E alone (400 IU/day) vs. vitamin E (400 IU/day) and pioglitazone (30 mg/day) in nondiabetic, noncirrhotic subjects with NASH. Metabolic functions were assessed by a 2-step, hyperinsulinemic (10 and 40 mU/m2/min) euglycemic clamp. RESULTS: A total of 10 patients were randomized to each arm. Two patients on combination therapy discontinued treatment; one because of pregnancy and the other because of hepatotoxicity. Treatment with vitamin E only produced a significant decrease in steatosis (mean grade, 2.2 vs. 1.4; P < .02). Compared with baseline, combination therapy produced a significant decrease in steatosis (mean, 2.3 vs. 1; P < .002), cytologic ballooning (1.3 vs. 0.2; P < .01), Mallory's hyaline (0.7 vs. 0.2; P < .04), and pericellular fibrosis (1.2 vs. 0.6; P < .03). Although vitamin E had no significant effects, combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid (FFA) and insulin. The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning. CONCLUSIONS: A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology. The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels.

3-Hydroxybutyric Acid↗

Induction of the differentiation of HL-60 promyelocytic leukemia cells by vitamin E and other antioxidants in combination with low levels of vitamin D3: possible relationship to NF-kappaB.

Epidemiological studies have provided evidence that diets rich in antioxidant nutrients may reduce the risk of cancer. To evaluate the possibility that dietary phytochemicals with antioxidant potential would create an environment capable of affecting the differentiation of HL-60 leukemia cells, we measured the effects of vitamin E and other dietary antioxidants on the differentiation produced by low levels of vitamin D3 and analogs thereof. Vitamin E succinate and other antioxidant compounds (ie butylated hydroxyanisole, beta-carotene and lipoic acid) used alone had no significant effect on the differentiation of HL-60 cells; however, these agents markedly increased the differentiation produced by vitamin D3. Previous studies from this laboratory have shown that a sequence-specific antisense phosphorothioate oligonucleotide to the Rel A subunit of NF-kappaB enhanced the differentiation of HL-60 cells produced by several inducing agents. Consistent with these observations, vitamin E succinate caused a marked reduction in the nuclear content of NF-kappaB both in the presence and absence of vitamin D3. These findings suggest that NF-kappaB may be a factor in regulating the differentiation of myeloid leukemia cells. The results also indicate that combinations of vitamin D3 and analogs thereof with dietary antioxidants may be useful in overcoming the differentiation block present in acute promyelocytic leukemia cells.

Antioxidants↗

Effects of vitamin E and different energy sources on vitamin E status, milk quality and reproduction in transition cows.

We investigated whether vitamin E supplementation and supplemental energy sources (fat or starch) influenced plasma and milk levels of vitamin E, and reproductive and other parameters in 28 Italian Friesian multiparous dry cows. From 14 days before expected calving to 7 days after, the animals were assigned to either basal diet (containing 1000 IU/day of vitamin E) or an extra 1000 IU/day of vitamin E (total 2000 IU). In addition they received either 0.5 kg/day of corn or 0.2 kg/day of calcium soaps. Plasma samples were collected 4 days before expected calving and 4 days after calving and analysed for alpha-tocopherol and cholesterol. Milk yield as well as the composition, somatic cell count (SCC) and alpha-tocopherol of milk were determined 7 and 14 days after calving. Milk yield and composition were unaffected by treatments. SCC was significantly lower in (SCC Log 4.62 versus Log 5.1, P < 0.01) 2000 IU/day animals than in the 1000 IU/day group. Milk alpha-tocopherol was higher (P < 0.001) in animals receiving 2000 IU/day (1.11 vs. 0.65 microgram/ml, P < 0.01). Plasma alpha-tocopherol in animals receiving 2000 IU/day was also higher (P < 0.001) than in cows receiving 1000 IU/day (4.85 vs. 3.25 micrograms/ml), but was not affected by dietary energy source. Number of services and days to conception were lower (P < 0.01) in the 2000 IU vitamin E supplemented cows. To conclude, dietary vitamin E supplementation to periparturient dairy cows increased plasma and milk vitamin E, decreased SCC in milk, and improved fertility but different energy sources had no effect on any measured variable.

Animals↗

Vitamin D receptor: mechanisms for vitamin D resistance in renal failure.

1,25-dihydroxyvitamin D [1,25(OH)2D3], the hormonal form of vitamin D, controls serum levels of parathyroid hormone (PTH) and parathyroid hyperplasia. Both 1,25(OH)2D3 actions involve regulation of gene transcription by the 1,25(OH)2D3/vitamin D receptor (VDR) complex. In advanced renal failure, in addition to low serum 1,25(OH)2D3 and reduced parathyroid vitamin D receptor content, several mechanisms downstream from 1,25(OH)2D3/VDR complex formation contribute to the impairment of 1,25(OH)2D3 action, including reduced levels of the retinoid X receptor, RXR, with the consequent reduction in VDR/RXR heterodimer formation, and accumulation of uremic toxins and increases in nuclear levels of calreticulin, two processes that impair the binding of the VDR/RXR complex to vitamin D responsive elements in vitamin D-regulated genes. VDR/RXR-heterodimer formation and its binding to DNA is critical for 1,25(OH)2D3 regulation of gene transcription. Early interventions with 1,25(OH)2D3 could delay the onset of vitamin D resistance by preventing both 1,25(OH)2D3 deficiency and its critical consequence, reduction in VDR content. Once established, vitamin D resistance could be counteracted by vitamin D analogs. While their less calcemic properties make higher dosing safer, their specificity to recruit co-activator molecules to the transcriptional pre-initiation complex could compensate for reduced 1,25(OH)2D3/VDR by potentiating VDR-transactivation/transrepression of genes critical for normal PTH synthesis and parathyroid cell growth.

Animals↗

Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients.

Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin C infusion (500 mg, C) into the arterial blood line during dialysis on parameters of oxidative stress. In a short-term study, 24 patients were subjected to a single dialysis session with E, O, E with C, and O with C protocols. In a long-term study (12 weeks), 20 patients were randomized into groups with C and without C on each dialysis, and both groups had dialysis using O, E, and again O membrane for 4 weeks each. In the short-term study, thiobarbituric acid reacting substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no changes were observed in the other 3 protocols. In the long-term study, predialysis TBARS declined when using E both in the groups with C (p < 0.02) and without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline levels. The E membrane prevented an increase in lipid peroxidation during single dialysis, and long-term use of the E membrane also resulted in a decrease in the predialysis lipid peroxidation level. The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion. High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin E regeneration.

Adult↗