The effect of vitamin A deficiency and dietary alpha-tocopherol on the stability of rat-liver lysosomes.
Ontology highlight
ABSTRACT:
SUBMITTER: Roels OA
PROVIDER: S-EPMC1264647 | biostudies-other | 1965 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:An adequate alpha-tocopherol status is important for females at reproductive age. We studied the dietary intake and sources of alpha-tocopherol and alpha- and gamma-tocopherol status indicators in 14-19-year-old girls in Central Mozambique. We also explored factors associated with alpha- and gamma-tocopherol status. The participants (n 508) were from the cross-sectional ZANE Study that was conducted in 2010. We recruited two separate samples, one in January-February and the other in May-June. We collected venous blood samples and conducted 24 h dietary recall interviews. At the time of blood sampling, 11 % of participants were pregnant and 10 % were lactating. In the total sample, both seasons combined, the median intake of alpha-tocopherol was 6⋅7 mg/d, the mean plasma alpha- and gamma-tocopherol concentrations were 13⋅5 and 0⋅75 μmol/l, respectively, and the prevalence of vitamin E inadequacy (alpha-tocopherol <12 μmol/l) was 36⋅7 % (95 % CI: 31⋅9-42⋅0 %). Season and lactation status were significant predictors of alpha-tocopherol status regardless of which the three indicators (plasma concentration, alpha-tocopherol:total cholesterol ratio, gamma-tocopherol:alpha-tocopherol ratio) were used. Being a lactating mother was negatively associated and having a blood sample taken in January-February, when the main sources of alpha-tocopherol were mango and dark green leafy vegetables, was positively associated with alpha-tocopherol status. In conclusion, vitamin E inadequacy was common in Central Mozambique, and the status may fluctuate due to seasonal changes in the diet. We suggest that lactating mothers are specifically at risk of poor alpha-tocopherol status in resource-poor settings.
| S-EPMC10753459 | biostudies-literature
Project description:The role of vitamin E and selenium as protective agents against oxidative stress was evaluated by measuring liver chemiluminescence in situ. Weanling rats fed a vitamin E- and selenium-deficient diet showed liver chemiluminescence that was increased 60 and 100% over control values at 16 and 18 days respectively after weaning. At day 21, the double deficiency led to hepatic necrosis, as observed by optical and electron microscopy, and increased serum levels of lactate dehydrogenase and alanine aminotransferase. Single deficiencies, in either vitamin E or selenium, did not produce liver necrosis but increased liver chemiluminescence. Vitamin E deficiency led to a 23 and 50% increase in liver emission at days 18 and 20 respectively; selenium deficiency produced a 64% increase at day 16. The activity of liver selenium-glutathione peroxidase diminished to 13% of the control value in the rats fed doubly deficient and selenium-deficient diets. Activities of superoxide dismutase, catalase and non-selenium-glutathione peroxidase were not modified by the different diets. These results suggest that oxy-radical generation may play a major role in hepatic necrosis in vitamin E- and selenium-deficiency.
| S-EPMC1147716 | biostudies-other
Project description:Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central role in vitamin E homeostasis, preventing degradation of alpha-T by routing this lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding ATTP have been shown to cause a severe deficiency in alpha-T, which results in a progressive neurodegenerative spinocerebellar ataxia, known as ataxia with vitamin E deficiency (AVED). We have determined the high-resolution crystal structure of human ATTP with (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is sequestered deep in the hydrophobic core of the protein, implicating a large structural rearrangement for the entry and release of alpha-T. A comparison to the structure of a related protein, Sec14p, crystallized without a bona fide ligand, shows a possibly relevant open conformation for this family of proteins. Furthermore, of the known mutations that cause AVED, one mutation, L183P, is located directly in the binding pocket. Finally, three mutations associated with AVED involve arginine residues that are grouped together on the surface of ATTP. We propose that this positively charged surface may serve to orient an interacting protein, which might function to regulate the release of alpha-T through an induced change in conformation of ATTP.
| S-EPMC299775 | biostudies-literature
Project description:Non-alcoholic fatty liver disease is the most common liver disorder in developed countries, and its incidence is increasing in all population groups. As an antioxidant, vitamin E is effective in the treatment of non-alcoholic fatty liver disease, although the mechanism is still unclear. Methionine-choline deficient Wistar rats (n = 5) used as an experimental model of non-alcoholic fatty liver disease were fed a vitamin E-enriched diet (500 mg/kg) for 4 weeks. The effects were assessed by measuring lipid peroxidation, α-tocopherol levels, and the expression of α-tocopherol-related proteins in the liver. In vitamin E-treated methionine-choline deficient rats, lipid peroxidation was reduced, but liver histopathological changes were not improved. Hepatic α-tocopherol levels in these rats were significantly elevated compared to normal rats treated with vitamin E. Expression of liver α-tocopherol transfer protein in vitamin E-treated methionine-choline deficient rats was significantly repressed compared to methionine-choline deficient rats. The expression of liver cytochrome P450 4F2 and ATP-binding cassette transporter protein 1, involved in metabolism and transport of α-tocopherol, respectively, was significantly repressed in vitamin E-treated methionine-choline deficient rats. In methionine-choline deficient rats, vitamin E treatment altered the hepatic α-tocopherol-related protein expression, which may affect α-tocopherol status in the liver, leading to reduced lipid peroxidation.
| S-EPMC4042150 | biostudies-literature
Project description:Alpha-tocopherol (alpha-T) may affect biological processes by modulating mRNA concentrations. This study screened the responses of approximately 15,000 lung mRNAs to dietary alpha-T in mice. The lung was chosen as the target organ because it is subjected to cyclical variations in oxidant and inflammatory stressors and alpha-T has been implicated in their modulations. The analysis identified approximately 400 mRNAs sensitive to alpha-T status of lungs determined by dietary alpha-T. The female lung transcriptome appears to be more sensitive to the alpha-T status than that of the male lungs. Here, we focus on the induction of 13 cytoskeleton genes by dietary alpha-T because they were similarly induced in the male and the female lungs. Their inductions were confirmed by quantitative-real-time-polymerase chain reaction (qRT-PCR). Immunohistochemical analyses of three of the encoded proteins suggest that they are expressed in lung vasculature and alveolar regions. The data suggest that the lung alpha-T status may modulate cytoarchitecture of lungs.
| S-EPMC2782686 | biostudies-literature
Project description:The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction.
| S-EPMC4546625 | biostudies-literature
Project description:This review describes the pathogenesis, clinical presentation and biochemical perturbations found in privational (nutritional) rickets and pseudo-vitamin D deficiency rickets (PDDR), an autosomal recessive condition with loss of function mutations in CYP27B1. It may seem strange to combine a discussion on privational rickets and PDDR as a single topic, but privational rickets and PDDR present with similar clinical signs and symptoms and with similar perturbations in bone and mineral metabolism. Of interest is the characteristic lack of features of rickets at birth in infants with PDDR, a finding which has also been reported in infants born to vitamin D-deficient mothers. This highlights the independence of the fetus and neonate from the need for vitamin D to maintain calcium homeostasis during this period. The variable roles of vitamin D deficiency and dietary calcium deficiency in the pathogenesis of privational rickets are discussed and the associated alterations in vitamin D metabolism highlighted. Although PDDR is a rare autosomal recessive disorder, results of long-term follow-up are now available on the effect of treatment with calcitriol, and these are discussed. Areas of uncertainty, such as should affected mothers breastfeed their infants, are emphasized.
| S-EPMC4015456 | biostudies-other
Project description:Little is known about the distribution and determinants of circulating vitamin E levels in a German population. In this cross-sectional study we assessed the distribution of both α- and γ-tocopherol levels, identified their clinical and biochemical correlates, and assessed their relationships with a priori and a posteriori derived dietary patterns. Plasma α- and γ-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) with fluorescence detection in 641 individuals (mean-age: 61 years; 40.6% women). Correlates of both markers were determined using linear regression with backward selection. Using a validated food-frequency questionnaire (FFQ), an a priori defined vitamin E-rich dietary pattern was constructed, and three a posteriori derived dietary patterns were identified by principal component analysis. Each pattern was related to α- and γ-tocopherol levels using linear regression. Median concentrations of α- and γ-tocopherol were 31.54 μmol/L and 1.35 µmol/L, respectively. 57.6% of participants had α-tocopherol levels >30 µmol/L. Triglycerides, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, and vitamin E supplementation were identified as correlates of vitamin E levels. After excluding supplement users, a dietary pattern rich in meat, bread, fats, potatoes, and sugar/confectionery was inversely related to α-tocopherol levels (β, -0.032, SE = 0.016; p = 0.047). Prospective studies are warranted to evaluate the actual impact of the reported findings in terms of nutrition and health outcomes.
| S-EPMC5793231 | biostudies-literature
Project description:Vitamin E isoforms are essential nutrients that are widely used as dietary supplements and therapeutic agents for a variety of diseases. However, their pharmacokinetic (PK) properties remain poorly characterized, and high dosage animal studies may provide further information on their in vivo functions and pharmacological effects. In this study, alpha-tocopherol (α-toc) and delta-tocopherol (δ-toc) levels were measured in mouse plasma and tissues following their high dosage dietary supplementation. Average α-toc levels at 5, 10 and 20 g α-toc/kg diet increased over baseline levels 6-fold in plasma, 1.6-fold in brain, and 4.9-fold in liver. These elevated α-toc concentrations remained constant from 5 to 20 g α-toc/kg diet, rather than showing further increases across these dosages. No α-toc-related toxicity occurred at these high dosages, and strain-specific differences in liver and brain α-toc levels between Balb/cJ and C57Bl/6J mice were observed. Relatively high-dosage administration of dietary δ-toc for 1 or 4 weeks resulted in 6-30-fold increases in plasma and liver levels between dosages of 0.33 and 1.67 g δ-toc/kg diet. Co-administration of sesamin with δ-toc further increased δ-toc levels between 1.3- and 14-fold in plasma, liver, and brain. These results provide valuable PK information on high dosage α-toc and δ-toc in mouse and show that supplementation of sesamin with δ-toc further increases δ-toc levels over those seen with δ-toc supplementation alone.
| S-EPMC3397347 | biostudies-literature
Project description:Initiation of a vitamin A deficient diet in mid-gestation, maintained in the post-weaning diet is sufficient to cause liver and serum retinoid depletion. Wild type C57Bl/6J timed mated pregnant dams were administered either a defined vitamin A sufficient low fat (12 percent kcal from fat) diet or matched vitamin A deficient diet from embryonic day 10.5. Vitamin A sufficient offspring were weaned onto either a high fat diet (60 percent kcal from fat) or maintained on the low fat 12 percent kcal from fat diet for 11 weeks (14 weeks of age). Gestational vitamin A deficient offspring were maintained on the same vitamin A deficient diet until 14 weeks of age. The impact of the maternal diet on a post-weaning high fat diet was compared to a standard maternal breeder diet followed by the post-weaning high fat diet.
2016-10-12 | GSE87845 | GEO