Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

Wu D, Jiang Z, Gong B, Dou Y, Song M, Song X, Tian Y

Int Heart J. 2017 Oct 21;58(5):769-777. doi: 10.1536/ihj.16-279.

Abstract

In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 μg Vit E, or 1.5 mg/kg + 0.1 μg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 μmol/L FA, 25 μmol/L FA, 50 μmol/L FA, 10 mg/L Vit. E, and 50 μmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 μg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

Waniek S, di Giuseppe R, Plachta-Danielzik S, Ratjen I, Jacobs G, Koch M, Borggrefe J, Both M, Müller HP, Kassubek J, Nöthlings U, Esatbeyoglu T, Schlesinger S, Rimbach G, Lieb W

Nutrients. 2017 Oct 18;9(10). pii: E1143. doi: 10.3390/nu9101143.

Abstract

We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α- tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21-2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23-2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.

Wu H, Zhang C, Wang Y, Li Y

Paediatr Respir Rev. 2017 Oct 16. pii: S1526-0542(17)30093-3. doi: 10.1016/j.prrv.2017.08.002.

Abstract

Asthma is a heterogeneous disease with multiple phenotypes. Epidemiologic studies suggest a close relationship between vitamin E and the occurrence of asthma, wheezing and atopic conditions during childhood. Previous results on its effects have been conflicting. The aim of this meta-analysis was to critically examine the current evidence on the association of vitamin E with childhood asthma and wheezing. We searched electronic databases for observational studies in English-language journals published from 2000 to 2016. The initial search found 420 titles; nineteen studies were eligible according to the abstracts and details, which included reporting asthma or wheeze as an outcome. None of the articles included in this meta-analysis reported side effects of vitamin E supplementation during pregnancy. This meta-analysis found that vitamin E supplementation during pregnancy influenced the risk of asthma. To better understand the effectiveness and safety of vitamin E in children with asthma, large-scale, well-designed and randomized controlled trials are needed.

Paunović MG, Matić MM, Ognjanović BI, Saičić ZS

Toxicol Ind Health. 2017 Oct;33(10):746-756. doi: 10.1177/0748233717725480.

Abstract

Cadmium (Cd) is a major environmental pollutant, which exerts adverse effects mainly by inducing oxidative stress. Coenzyme Q₁₀ (CoQ₁₀) and vitamin E (VE), naturally occurring antioxidants, improve health condition by inactivating free radicals and enhancing antioxidative defence. The aim of our study was to investigate the protective role of CoQ₁₀ and/or VE pretreatment against Cd-induced haematotoxicity. Wistar albino rats were intramuscularly injected with CoQ₁₀ (20 mg/kg b.w.) and/or VE (20 IU/kg b.w.) or with saline (control group). After 24 h, Cd was injected intraperitoneally (0.4 mg/kg b.w.) and 1 day after, animals were sacrificed. Acute Cd intoxication caused significant changes in haematological and biochemical parameters and altered the glutathione cycle, leading to the formation of lipid peroxidation, while the concentrations and activities of antioxidants (vitamins C and E, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were decreased. CoQ₁₀ and/or VE significantly maintained these values to near-normal levels, afforded additional protection by reducing lipid peroxidation and improved the levels of antioxidants in the blood. Plasma CoQ₁₀ and VE levels negatively correlated with oxidative damage parameters while positively correlated with antioxidative defence parameters. Regarding their effects, CoQ₁₀ and VE were in synergistic interaction. The present study suggested that CoQ₁₀ and VE combination may be beneficial in protecting from Cd-induced haematotoxicity and may be used as a preventive against acute Cd intoxication of exposed people.

Osipiani B, Machavariani T, Gvamichava T, Gachechiladze I, Nikobadze E

Georgian Med News. 2017 Oct;(271):102-106.

Abstract

It is commonly known that in diabetes mellitus the risk of cardiovascular diseases and mortality increases. The purpose of this study was to determine the specific features of the morphological restructuring of the myocardium in the early stage of experimental diabetes and use the combined impact of powerful antioxidants (Vitamin C and Vitamin E) on the rat myocardium in conditions of alloxan-induced diabetes. The experimental animals were divided into three groups: 40 rats were the target, and 20 rats were the control. Target rats were divided into 2 groups: 1) group consisted of 20 rats with alloxan-induced diabetes; 2) group of 20 rats, which after confirmation of alloxan-induced diabetes, during 4 weeks were given intramuscularly vitamins C and E. The material was studied by histological and electron microscopic methods of investigation In the early stage of DM development, structural alterations in the cardiomyocytes and microcirculatory channels can be observed in the heart. Aggregation and agglutination of red blood cells and endothelial cell destruction were found in some vessels. In the study the result of combined therapy of Vitamin C and Vitamin E is a decrease in blood glucose levels, increases of endothelial proliferation, promoting the formation of new capillaries and further reduction of the structural changes of cardiomyocytes. Apperently through its antioxidative and anti-inflammatory activity Vitamins C and E stabilizes the metabolism processes in the vascular system and consequently, improvement of the organ function.

Koriem KMM, Arbid MS, Gomaa NE

Indian J Clin Biochem. 2017 Oct;32(4):446-452. doi: 10.1007/s12291-016-0623-4.

Abstract

The favism is a metabolic disease that characterized with an acute hemolytic anemia where α-tocopherol is a type of tocopherol accumulated inside the human body. The objective of such a study was established to evaluate the effect of α-tocopherol in favism disorders. A total of 75 human cases were divided into 5 groups as follow; group 1 normal cases without any treatment and group 2 normal cases orally administrated α-tocopherol (200 mg/kg) once a day over 30 days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism patients orally administrated 100 and 200 mg α-tocopherol/kg, respectively once a day over 30 days period. The results obtained revealed that oral administration of α-tocopherol into normal cases over 30 days period did not induce any biological change. In favism, hemoglobin, hematocrit, red and white blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein, albumin, globulin, aspartate and alanine aminotransferases, blood glutathione, superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous, sodium, potassium and chloride levels were significantly decreased. On the other hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper and iron, malondialdehyde levels showed significant increase in favism. Supplementation with α-tocopherol into favism restores all the above mentioned parameters to approach the normal levels. Also, α-tocopherol has anti-apoptotic effect in favism. In conclusion, α-tocopherol attenuates minerals disturbance, oxidative stress and apoptosis occurring in favism.

Tan DM, Fu JY, Wong FS, Er HM, Chen YS, Nesaretnam K

Nanomedicine (Lond). 2017 Oct;12(20):2487-2502. doi: 10.2217/nnm-2017-0182. Epub 2017 Sep 20.

Abstract

AIM:

To develop 6-O-palmitoyl-ascorbic acid-based niosomes targeted to transferrin receptor for intravenous administration of tocotrienols(T3) in breast cancer.

MATERIALS & METHODS:

Niosomes were prepared using film hydration and ultrasonication methods. Transferrin was coupled to the surface of niosomes via chemical linker. Nanovesicles were characterized for size, zeta potential, morphology, stability and biological efficacy.

RESULTS:

When evaluated in MDA-MB-231 cells, entrapment of T3 in niosomes caused 1.5-fold reduction in IC₅₀ value compared with nonformulated T3. In vivo, the average tumor volume of mice treated with tumor-targeted niosomes was 12-fold lower than that of untreated group, accompanied by marked downregulation of three genes involved in metastasis.

CONCLUSION:

Findings suggested that tumor-targeted niosomes served as promising delivery system for T3 in cancer therapy.

Miyashima Y, Shibata M, Honma Y, Matsuoka H, Hiura M, Abe S, Harada M

Intern Med. 2017 Oct 11. doi: 10.2169/internalmedicine.8767-16.

Abstract

A 49-year-old woman with a history of heavy alcohol drinking was admitted to our hospital due to jaundice and abdominal distention. A blood test showed leukophilia, mild hypoalbuminemia, hyperbilirubinemia, hepatobiliary injury and coagulopathy. Image studies showed an extremely enlarged fatty liver and splenomegaly. The Japan alcoholic hepatitis score and Maddrey’s discriminant function were 10 and 54 points, respectively. We diagnosed her with severe alcoholic hepatitis and treated her with corticosteroids, but her liver function did not improve. We therefore administered the vitamin E product tochopheryl acetate (150 mg/day) as an add-on therapy, after which her leukophilia, liver enzymes and coagulopathy improved immediately.

Shibata A, Kobayashi T, Asai A, Eitsuka T, Oikawa S, Miyazawa T, Nakagawa K

J Nutr Biochem. 2017 Oct;48:44-50. doi: 10.1016/j.jnutbio.2017.06.009. Epub 2017 Jun 24.

Abstract

Previous studies have demonstrated that tocotrienol (T3) has antiatherogenic effects. However, the T3 preparations used in those studies contained considerable amounts of tocopherol (Toc), which might affect the biological activity of T3. There is little information on the effect of highly purified T3 on atherosclerosis formation. This study investigated the effect of high-purity T3 on atherosclerotic lesion formation and the underlying mechanisms. Male apolipoprotein E knockout (apoE-KO) mice were fed a cholesterol-containing diet either alone or supplemented with T3 concentrate (Toc-free T3) or with α-Toc for 12 weeks. ApoE-KO mice fed the 0.2% T3-supplemented diet showed reduced atherosclerotic lesion formation in the aortic root. The 0.2% T3 diet induced Slc27a1 and Ldlr gene expression levels in the liver, whereas the α-Toc-supplemented diet did not affect those expression levels. T3 was predominantly deposited in fat tissue in the T3 diet-fed mice, whereas α-Toc was preferentially accumulated in liver in the α-Toc diet-fed mice. Considered together, these data demonstrate that dietary T3 exerts anti-atherosclerotic effect in apoE-KO mice. The characteristic tissue distribution and biological effects of T3, that are substantially different from those of Toc, may contribute to the antiatherogenic properties of T3.

Alawin OA, Ahmed RA, Dronamraju V, Briski KP, Sylvester PW

J Nutr Biochem. 2017 Oct;48:83-93. doi: 10.1016/j.jnutbio.2017.06.013. Epub 2017 Jul 10.

Abstract

Overexpression of heregulin, a potent ligand that activates HER3 and HER4 receptors, plays a significant role in the development of chemotherapy resistance in breast cancer patients. Exosomes released from cancer cells are small vesicles originating from the outward budding of lipid rafts that carry various mitogenic proteins that then act locally in an autocrine/paracrine manner to stimulate cancer cell growth. Since the anticancer activity of γ-tocotrienol has been shown to be mediated in part through the disruption of lipid rafts, studies were conducted to determine the effect of γ-tocotrienol on exosomes mitogenic biopotency. Exosomes isolated from the media of cultured T47D breast cancer cells were found to stimulate T47D cell growth in a dose-dependent manner. These growth stimulating effects were due to the high levels of heregulin contained in the exosomes that act to stimulate HER3 and HER4 activation, heterodimerization and mitogenic signaling. Exposure to 5 μM γ-tocotrienol resulted in the selective accumulation and disruption in the integrity of the lipid raft microdomain and a corresponding decrease in exosome heregulin content and mitogenic biopotency. These findings provide strong evidence indicating that the anticancer effects of γ-tocotrienol are mediated, at least in part, by directly disrupting HER dimerization and signaling within the lipid rafts and indirectly by reducing exosome heregulin content and subsequent autocrine/paracrine mitogenic stimulation.