Monthly Archives: May 2020

Opinion: Vaping and Vitamin E: What Went Wrong?

Many people struggle to quit smoking cigarettes to prevent and slow lung diseases, such as chronic obstructive pulmonary disorder.
Nicotine is such an addictive substance that in a desperate attempt to get healthy many people turned to e-cigarettes, which delivered the nicotine in a vapor instead of smoke. But instead of getting healthier, these former smokers got worse. In addition, healthy, young people started experimenting with recreational vaping, and despite their health and youth, they, too, developed serious lung problems.

Why did this happen? What went wrong?

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Nodular Panniculitis in a Cat With High Alpha Tocopherol Concentration in Serum

Martin Steffl, Nadine Nautscher, Alexander Kröpfl, Michael Granvogl

Vet Med Sci . 2020 May 18. doi: 10.1002/vms3.286. Online ahead of print.

Abstract

A 5-year-old male neutered domestic shorthair cat suffered from recurrent solitary nodules in different subcutaneous body regions. Nodules were surgically removed and each time histopathological diagnosis was fat necrosis and fibrosing to pyogranulomatous panniculitis. After the second surgery the alpha (α)-tocopherol concentration in serum of the cat was examined and the result (21 mg/L) exceeded the upper limit of the reference interval (3-11 mg/L). Vitamin E amount in diet fed solely in the past was checked as studies have shown that vitamin E amounts in food significantly influence vitamin E concentrations in serum. For comparative purposes, α-tocopherol concentrations were determined in sera of healthy control cats. Additionally, vitamin E amount in wet food from different manufacturers was analysed using gas chromatography coupled to mass spectrometry (GC-MS). The results showed that the diet did not have higher vitamin E amounts compared to other diets. All control cats had similar high serum α-tocopherol concentrations. We conclude that panniculitis can occur despite high serum α-tocopherol concentrations in cats. Further studies are needed to redefine reference values of α-tocopherol in serum of cats.

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Improving tumor hypoxia and radiotherapy resistance via in situ nitric oxide release strategy

Tu J, Tu K, Xu H, Wang L, Yuan X, Qin X, Kong L, Chu Q, Zhang Z

Eur J Pharm Biopharm. 2020 May;150:96-107. doi: 10.1016/j.ejpb.2020.03.003. Epub 2020 Mar 6.

Abstract

Radiation therapy remains one of the main treatments for cancer. However, conventional radiotherapy not only manifests a low radiation accumulation in the tumor site, but also displays numerous negative effects. The most serious clinical problem is the radiotherapy resistance leading to cancer deterioration. As an important gaseous signal molecule, nitric oxide (NO) has been widely studied for its role in regulating angiogenesis, improving hypoxia, and inhibiting tumor growth. However, due to the unstable characteristic, the application of NO in cancer therapy is still limited. Here, we designed a micellar system formed by a NO donor, D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-NO, for enabling sustained NO release to efficiently deliver NO into the tumor area. TPGS-NO could accumulate in the tumor site for extended circulation, thereby releasing NO to exert antitumor effects and enhance radiotherapy effects under low-oxygen conditions. It demonstrated the increased sensitivity of radiotherapy through enhancing tumor angiogenesis appropriately reducing tumor area hypoxia, which significantly induced tumor cell apoptosis and inhibited its repair during radiation. This work may show great potential in synergistic radiotherapy against cancer by facile NO donor administration.

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The simultaneous quantification of phytosterols and tocopherols in liposomal formulations using validated atmospheric pressure chemical ionization- liquid chromatography -tandem mass spectrometry

Poudel A, Gachumi G, Badea I, Bashi ZD, El-Aneed A

J Pharm Biomed Anal. 2020 May 10;183:113104. doi: 10.1016/j.jpba.2020.113104. Epub 2020 Jan 9.

Abstract

A novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously quantify phytosterols (brassicasterol, campesterol, stigmasterol and β-sitosterol) and tocopherols (alpha, beta, gamma and delta) entrapped in the lipid bilayer of a liposomal formulation. Apart from liposomes (a pharmaceutical product), the developed method was able to quantify target analytes in agricultural products, thus showing wide applications. Atmospheric pressure chemical ionization (APCI) was employed due to the enhanced ionization of phytosterols and tocopherols in comparison to electrospray ionization. Unlike published work, the chromatographic conditions were modified to simplify the analytical approach. For the first time, a simple isocratic elution (acetonitrile:methanol 99:1 v/v) was utilized for the separation of four phytosterols and four tocopherols in a single run. A substantially better baseline separation of phytosterols were obtained in comparison to reported methods by using poroshell C18 column. The method has a total run time of 7 min, which is the shortest run time among all reported quantitative methods for the simultaneous determination of four phytosterols and four tocopherols. Calibration curves for all phytosterols were linear in the range of 0.05-10 μg/mL. In the case of tocopherols, alpha tocopherol showed linear response in the range of 0.25-10 μg/mL. However, gamma and delta tocopherols exhibited quadratic relationship in the same concentration range (0.25-10 μg/mL). Validation parameters met the International Conference on Harmonization (ICH) guidelines in terms of selectivity, accuracy, precision, repeatability, sensitivity, matrix effects, dilution integrity and stability. The method was, for the first time, successfully applied for the quantifying phytosterols and tocopherols entrapped inside liposomes. An interesting chromatographic phenomenon was observed during sample analysis. Alpha tocopherol (entrapped in the liposomal lipid bilayer) was found to elute at two retention times, 2.53 min and 3.60 min. Such dual separation was not observed in calibration standards and quality controls. It was concluded that the chiral recognition ability of liposomes made up of phosphatidylcholine separated the enantiomers of alpha tocopherol, giving rise to two peaks at two different retention time. To sum, the reported novel LC-MS/MS method addresses three major analytical shortcomings, namely i)longer run time, ii)complex gradient elution and iii)poor baseline separation of phytosterols and tocopherols.

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Upregulation of pERK and c-JUN by γ-Tocotrienol and Not α-Tocopherol Are Essential to the Differential Effect on Apoptosis in Prostate Cancer Cells

Christine Moore, Victoria E Palau, Rashid Mahboob, Janet Lightner, William Stone, Koyamangalath Krishnan

BMC Cancer . 2020 May 15;20(1):428. doi: 10.1186/s12885-020-06947-6.

Abstract

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3.

Methods: The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control.

Results: The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT.

Conclusions: c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.

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Effects of Fatty Acids and Vitamin E in Larval Diets on Development and Performance of Queensland Fruit Fly

Tahereh Moadeli, Fleur Ponton, Phillip W Taylor

J Insect Physiol . 2020 May 15;104058. doi: 10.1016/j.jinsphys.2020.104058. Online ahead of print.

Abstract

Tephritid fruit flies are commonly reared on artificial larval diets for laboratory studies and for sterile insect technique pest management programs. While significant effort has been invested in developing artificial larval diets, surprisingly little is known about the specific nutritional requirements of tephritid flies. Recently developed gel larval diets have provided new opportunities for nutritional studie s in Queensland fruit fly, Bactrocera tryoni (‘Q-fly’). Wheat germ oil (WGO) is the main source of fatty acids and vitamin E in this diet, and is key for production of high-quality adults. To identify the importance of nutritional components of WGO for Q-fly productivity and quality, linoleic, linolenic, oleic and palmitic fatty acids as well as α-tocopherol (vitamin E) were included in the diet individually and in combination. Diets that included all of the tested fatty acids or just unsaturated fatty acids performed as well as diets containing WGO in most quality control parameters except fecundity, and addition of vitamin E reduced the pupal productivity. Considering individual fatty acids, larval diets containing only linolenic acid produced adults with higher percentage of fliers than did larval diets containing only palmitic acid or oleic acid. Compared with diets containing WGO, nutritional requirements for egg production in Q-fly were not entirely met by either grouped fatty acids or individual polyunsaturated, monounsaturated or saturated fatty acids, however, diets containing linoleic acid alone produced more eggs than any other fatty acid. The present study is a significant advance in understanding of the role of fatty acids as a component of WGO in larval diet in meeting the needs of developing Q-fly for somatic performance, but highlight also that other, untested, components of WGO appear to be important for reproduction.

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Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-β1/MMP-2 signaling pathway

Farias JS, Santos KM, Lima NKS, Cabral EV, Aires RS, Veras AC, Paixão AD, Vieira LD

Arch Biochem Biophys. 2020 May 15;684:108306. doi: 10.1016/j.abb.2020.108306. Epub 2020 Feb 17.

Abstract

Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

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Alterations of Serum Vitamin E and Vitamin A Concentrations of Ponies and Horses During Experimentally Induced Obesity

Carola Schedlbauer, Dominique Blaue, Jens Raila, Ingrid Vervuert

J Anim Physiol Anim Nutr (Berl) . 2020 May 14. doi: 10.1111/jpn.13385. Online ahead of print.

Abstract

Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum α-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (±SD) % BW gain achieved during two years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. Serum α-tocopherol increased significantly in ponies and horses during excess energy intake and circulating α-tocopherol levels correlated positively with α-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.

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Comparative Study of the Oxidation Stability of High Oleic Oils and Palm Oil During Thermal Treatment

Ziyang Xu, Zhan Ye, Youdong Li, Jinwei Li, Yuanfa Liu

J Oleo Sci . 2020 May 14. doi: 10.5650/jos.ess19307. Online ahead of print.

Abstract

For the controversy still existed about the oxidation stability of the high oleic oils compared with palm oil (PO), this study was aimed to explore the possible reason causing the controversies. Total polar compounds (TPC) was used to evaluate the oxidation stability of oils. Results showed there exist two kinds of lineal changes about the content of total polar compounds (TPC) in each oil, which were closely linked with the fatty acid composition and the tocochromanols content. The possible influence of the initial quality of oils also should be considered. The TPC of high oleic peanut oil (HOPO), high oleic sunflower oil (HOSO), high oleic rapeseed oil (HORO) and PO increased slowly at the initial period mainly owing to the antioxidation of tocochromanols, then sharply after 24, 48, 36 and 72 h respectively, when tocochromanols in each oil almost reduced below the detection limit. After that, the major factor would be fatty acids, particularly PUFA. It showed that the major tocochromanols in different oils (e.g. α, γ-tocotrienols in PO, α, γ-tocopherols in HORO and HOPO, and α-tocopherols in HOSO), could impose the main effects of inhibiting the TPC generation in the initial thermal treatment. The TPC in HORO significantly increased after 84 hours of heat process, which might be caused by the higher content of the polyunsaturated fatty acids (PUFA) (i.e. C18:2 and C18:3). However, the content of the saturated fatty acid (SFA) did not show statistically significant change during the thermal treatment.

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Vitamin E Promotes the Inverse Hexagonal Phase via a Novel Mechanism: Implications for Antioxidant Role

Paul E Harper, Andres T Cavazos, Jacob J Kinnun, Horia I Petrache, Stephen R Wassall

Langmuir . 2020 May 12;36(18):4908-4916. doi: 10.1021/acs.langmuir.0c00176. Epub 2020 Apr 30.

Abstract

Vitamin E (α-tocopherol) and a range of other biological compounds have long been known to promote the HII (inverted hexagonal) phase in lipids. Now, it has been well established that purely hydrophobic lipids such as dodecane promote the HII phase by relieving extensive packing stress. They do so by residing deep within the hydrocarbon core. However, we argue from X-ray diffraction data obtained with 1-palmitoyl-2-oleoylphosphatidylcholine (POPE) and 1,2-dioleoylphosphatidylcholine (DOPE) that α-tocopherol promotes the HII phase by a different mechanism. The OH group on the chromanol moiety of α-tocopherol anchors it near the aqueous interface. This restriction combined with the relatively short length of α-tocopherol (as compared to DOPE and POPE) means that α-tocopherol promotes the HII phase by relieving compressive packing stress. This observation offers new insight into the nature of packing stress and lipid biophysics. With the deeper understanding of packing stress offered by our results, we also explore the role that molecular structure plays in the primary function of vitamin E, which is to prevent the oxidation of polyunsaturated membrane lipids.

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