Vitamin E analogs limit in vitro oxidant damage to bovine mammary endothelial cells

M J Kuhn, L M Sordillo

J Dairy Sci . 2021 Mar 24;S0022-0302(21)00448-3. doi: 10.3168/jds.2020-19675. Online ahead of print.

Abstract

Diseases that occur during the transition period are exacerbated when cows are unable to cope with an increased pro-oxidant load that results in oxidative stress. Dairy cattle are routinely supplemented with the vitamin E analog α-tocopherol to mitigate the severity of oxidative stress. Nonetheless, oxidative stress remains a disease predisposing condition for many dairy cattle. A better method of optimizing the antioxidant functions of vitamin E is needed. α-Tocopherol is only 1 of 8 analogs of vitamin E, all of which have varying antioxidant properties in other mammals, albeit a shorter physiological half-life compared with α-tocopherol. A primary bovine mammary endothelial cell oxidant challenge model was used to determine functions of certain vitamin E analogs. The aim of this study was to determine if other analogs, namely γ-tocopherol or γ-tocotrienol, have antioxidative functions in bovine cells and if these functions may protect cellular viability and endothelial function from oxidant damage. Physiological (10 μM) and supraphysiological (50 μM) concentrations of γ-tocopherol and γ-tocotrienol had a greater capacity to reduce accumulated reactive oxygen species derived from a nitric oxide donating pro-oxidant antagonist, when compared with α-tocopherol, after 30 min to 6 h of treatment. Further, γ-tocotrienol (10 μM) decreased cell cytotoxicity to a greater amount than other analogs at like concentrations, whereas γ-tocopherol (10 μM) reduced lipid peroxidation and apoptosis more effectively than other analogs. Last, α-tocopherol (5 and 10 μM) and γ-tocopherol (5 and 10 μM) significantly slowed pro-oxidant induced loss of endothelial cell barrier integrity over a 48-h period using an electrical cell-substrate impedance sensing system. Concerningly, γ-tocotrienol drastically reduced the endothelial barrier integrity at only 5 μM despite no apparent effect on cellular viability at like concentrations. γ-Tocotrienol, however, was also the only analog to show significant cytotoxicity and reductions in viability at supraphysiological doses (25 and 50 μM). Our results suggest that γ-tocopherol has antioxidant activities that reduces cellular damage and loss of function due to oxidant challenge as effectively as α-tocopherol. These data set the foundation for further investigation into the antioxidant properties of vitamin E analogs in other bovine cells types or whole animal models.

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Production of tocotrienols in seeds of cotton (Gossypium hirsutum L.) enhances oxidative stability and offers nutraceutical potential

Shanmukh S Salimath, Trevor B Romsdahl, Anji Reddy Konda, Wei Zhang, Edgar B Cahoon, Michael K Dowd, Thomas C Wedegaertner, Kater D Hake, Kent D Chapman

Plant Biotechnol J . 2021 Jan 25. doi: 10.1111/pbi.13557. Online ahead of print.

Abstract

Upland cotton (Gossypium hirsutum L.) is an economically important multi-purpose crop cultivated globally for fibre, seed oil and protein. Cottonseed oil also is naturally rich in vitamin E components (collectively known as tocochromanols), with α- and γ-tocopherols comprising nearly all of the vitamin E components. By contrast, cottonseeds have little or no tocotrienols, tocochromanols with a wide range of health benefits. Here, we generated transgenic cotton lines expressing the barley (Hordeum vulgare) homogentisate geranylgeranyl transferase coding sequence under the control of the Brassica napus seed-specific promoter, napin. Transgenic cottonseeds had ~twofold to threefold increases in the accumulation of total vitamin E (tocopherols + tocotrienols), with more than 60% γ-tocotrienol. Matrix assisted laser desorption ionization-mass spectrometry imaging showed that γ-tocotrienol was localized throughout the transgenic embryos. In contrast, the native tocopherols were distributed unequally in both transgenic and non-transgenic embryos. α- Tocopherol was restricted mostly to cotyledon tissues and γ-tocopherol was more enriched in the embryonic axis tissues. Production of tocotrienols in cotton embryos had no negative impact on plant performance or yield of other important seed constituents including fibre, oil and protein. Advanced generations of two transgenic events were field grown, and extracts of transgenic seeds showed increased antioxidant activity relative to extracts from non-transgenic seeds. Furthermore, refined cottonseed oil from the two transgenic events showed 30% improvement in oxidative stability relative to the non-transgenic cottonseed oil. Taken together, these materials may provide new opportunities for cottonseed co-products with enhanced vitamin E profile for improved shelf life and nutrition.

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Role of Palm Oil Vitamin E in Preventing Pre-eclampsia: A Secondary Analysis of a Randomized Clinical Trial Following ISSHP Reclassification

Nurul Afzan Aminuddin, Rosnah Sutan, Zaleha Abdullah Mahdy

Front Med (Lausanne) . 2021 Jan 21;7:596405. doi: 10.3389/fmed.2020.596405. eCollection 2020.

Abstract

Background: Preeclampsia is a significant cause of maternal and perinatal mortality worldwide. Oxidative stress plays a key role in its pathophysiology, hence antioxidants such as tocotrienol may be preventive against preeclampsia. In 2018, the ISSHP revised the definition of preeclampsia. In accordance with the new definition, we report a secondary data analysis from a clinical trial comparing palm oil vitamin E in the form of tocotrienol-rich fraction (TRF) against placebo, in preventing preeclampsia. Method: A randomized double-blind controlled trial was conducted in 2002-2005 to assess the benefits of TRF in preeclampsia prevention. A total of 299 primigravidae were recruited. The intervention group was supplemented with TRF 100 mg daily in super-olein capsules, whereas the placebo group was prescribed super-olein capsules without TRF, beginning from 12 to 16 gestational weeks until delivery. The primary outcome measure was incidence of preeclampsia. Results: The total incidence of pregnancy induced hypertension (PIH) was 5%, whereas the incidence of preeclampsia was 2.3%. The odds of developing PIH (adjusted OR 0.254; 95% CI: 0.07-0.93; p-value 0.038) and preeclampsia (adjusted OR 0.030; 95% CI: 0.001-0.65; p-value 0.025) were significantly lower in the TRF arm compared to the placebo arm. Conclusion: Antenatal supplementation with palm oil vitamin E in the form of TRF is associated with significant reductions in the incidence of preeclampsia and PIH in a single urban tertiary hospital. Palm oil vitamin E deserves further scrutiny as a potential public health preventive measure against preeclampsia and PIH.

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Synthesis of [ 18 F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Peter Roselt, Carleen Cullinane, Wayne Noonan, Hassan Elsaidi, Peter Eu, Leonard I Wiebe

Molecules . 2020 Dec 3;25(23):5700. doi: 10.3390/molecules25235700.

Abstract

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.

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Epidermal Growth Factor and Tocotrienol-Rich Fraction Cream Formulation Accelerates Burn Healing Process Based on Its Gene Expression Pattern in Deep Partial-Thickness Burn Wound Model

Hui-Fang Guo, Razana Mohd Ali, Roslida Abd Hamid, Sui Kiat Chang, Mohammed Habibur Rahman, Zaida Zainal, Huzwah Khaza'ai

Int J Low Extrem Wounds . 2020 Nov 26;1534734620971066. doi: 10.1177/1534734620971066. Online ahead of print.

Abstract

Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of IL-6 (interluekin-6), TNF-α (tumor necrosis factor-α) and iNOS (inducible nitric oxide synthase) throughout the whole healing process. TGF-β1 (transforming growth factor-β) and VEGF-A (vascular endothelial growth factor-A) were reduced on day 14 postburn. On the contrary, increased expression of Collagen-1 in the early stage of wound healing was observed with no effects on epidemal growth factor receptor (EGFR). The results showed beneficial application of EGF + TRF cream in the treatment of burn wound since it accelerated wound healing by relieving oxidative stress, decreasing inflammation, and promoting proper tissue modelling in the burn wound.

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γ- and δ-Tocotrienols interfere with senescence leading to decreased viability of cells

Maria Janubova, Jozef Hatok, Katarina Konarikova, Ingrid Zitnanova

Mol Cell Biochem . 2020 Oct 30. doi: 10.1007/s11010-020-03954-w. Online ahead of print.

Abstract

Senescence is an irreversible permanent cell cycle arrest accompanied by changes in cell morphology and physiology. Bioactive compounds including tocotrienols (vitamin E) can affect important biological functions. The aim of this study was to investigate how γ- and δ-tocotrienols can affect stress-induced premature senescence. We established two different models of premature stress senescence by induction of senescence with either hydrogen peroxide or etoposide in human lung fibroblasts MRC-5 (ECACC, England). We observed increased percentage of cells with increased SA-β-galactosidase activity, decreased cell viability/proliferation and increased level of p21 in both models. In addition, γ-tocotrienol or δ-tocotrienol (both at concentrations of 150, 200 and 300 μM) were added to the cells along with the inductor of senescence (cotreatment). We have found that this cotreatment led to the decrease of cell viability/proliferation in both models of premature stress senescence, but did not change the percentage of senescent cells. Moreover, we detected no expression of caspase-3 or apoptotic DNA fragmentation in any models of premature stress senescence after the cotreatment with γ- as well as δ-tocotrienols. However, an increased level of autophagic protein LC-3 II was detected in cells with hydrogen peroxide-induced senescence after the cotreatment with γ-tocotrienol as well as δ-tocotrienol. In case of etoposide-induced senescence only δ-tocotrienol cotreatment led to an increased level of LC-3 II protein in cells. According to our work δ-tocotrienol is more effective compound than γ-tocotrienol.

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Achiote (Bixa orellana) Lipophilic Extract, Bixin, and δ-tocotrienol Effects on Lifespan and Stress Resistance in Caenorhabditis elegans

Darío R Gómez-Linton, Silvestre Alavez, Arturo Navarro-Ocaña, Angélica Román-Guerrero, Luis Pinzón-López, Laura J Pérez-Flores

Planta Med . 2020 Oct 29. doi: 10.1055/a-1266-6674. Online ahead of print.

Abstract

The onset of many degenerative diseases related to aging has been associated with a decrease in the activity of antistress systems, and pharmacological interventions increasing stress resistance could be effective to prevent the development of such diseases. Achiote is a valuable source of carotenoid and tocotrienols, which have antioxidant activity. In this work, we explore the capacity of an achiote seed extract and its main compounds to modulate the lifespan and antistress responses on Caenorhabditis elegans, as well as the mechanisms involved in these effects. Achiote lipophilic extract, bixin, and δ-tocotrienol were applied on nematodes to carry out lifespan, stress resistance, and fertility assays. The achiote seed extract increased the median and maximum lifespan up to 35% and 27% and increased resistance against oxidative and thermal stresses without adverse effects on fertility. The beneficial effects were mimicked by a bixin+δ-tocotrienol mixture. All the effects on lifespan and stress resistance were independent of caloric restriction but dependent on the insulin/insulin growth factor-1 pathway. This study could provide insights for further research on a new beneficial use of this important crop in health and nutraceutical applications beyond its use as a source of natural pigments.

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Possible modulation of nervous tension-induced oxidative stress by vitamin E

Noorah Saleh Al-Sowayan

Saudi J Biol Sci . 2020 Oct;27(10):2563-2566. doi: 10.1016/j.sjbs.2020.05.018. Epub 2020 May 15.

Abstract

Stress is an unavoidable part of human life that affects a majority of people: In 2018, 55% of Americans reported experiencing stress (Gallup Global Emotions, 2019). Various factors contribute to the emergence of nervous stress among individuals, including environmental, physical, and psychological stimuli. Physical and psychological issues arise as a result of stress, which is the subject of our research study, giving it significant practical value. Here, we have tested the possible correlation between increase in oxidation species and severe psychological issues at a community level. To understand any possible connections between these two parameters, tests were conducted on 200 rats that were divided into three general groups based on the duration of stress exposure. Each group was further divided into five smaller groups with 10-20 rats. Treatments were setup with or without vitamin E with periods of stress immobilization. Samples were then collected to conduct necessary analyses from control, experimental, and treatment groups. Immobilization stress types, i.e., acute and chronic stress, caused noticeably different physiological changes, especially with respect to nature and severity of response. Chronic stress induced different responses depending on the exposure period as well. Furthermore, vitamin E appeared to have a protective role due to its antioxidant nature, which highlights the need for investigations on oxidative stress-related disease treatment and prevention.

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A serum containing vitamins C & E and a matrix-repair tripeptide reduces facial signs of aging as evidenced by Primos® analysis and frequently repeated auto-perception

Karl Lintner, Francine Gerstein, Nowell Solish

J Cosmet Dermatol . 2020 Oct 26. doi: 10.1111/jocd.13770. Online ahead of print.

Abstract

Background: Allegations on the benefits of incorporating vitamin C, vitamin E, and combinations thereof in topical skincare formulations are mostly based on in vitro and ex vivo experiments and/or limited protocols of specific stress conditions (pollution, UV exposure, laser irradiation,…).

Objective: To evaluate the instrumentally measurable effects and quantitative consumer perceptions of a protective and reparative serum on a panel of volunteers under normal nonstressed conditions of use, employing FOITS technology and innovative self-assessment methods.

Method: In an open-label study women of ≥40 years with visible signs of photoaging applied a serum comprising l-ascorbic acid USP (15% w/v), tocopheryl acetate USP, and 5 ppm palmitoyl tripeptide-38 to the face once daily for 56 days. Skin roughness and isotropy changes were evaluated on days 0, 28, and 56, visual instrumental evaluation of skin-tone parameters was assessed on days 0 and 56. Subjects completed self-assessment questionnaires every third day of the trial period for radiance, homogeneity, and wrinkle appearance.

Results: Skin-roughness parameters decreased significantly by 8%-9% (P < .05) and subjects experienced a significant increase in skin isotropy (P < .05). Photographic analysis revealed significant improvements in skin tone, with a 9% decrease in redness and 8% increase in homogeneity (P < .0001 for both), in excellent agreement with subjects’ perception of significant improvements of radiance, complexion, and wrinkles.

Conclusion: The study confirms statistically significant correlation between objectively measured and quantitative subjectively perceived benefits of the bespoke serum containing antioxidants and a matrix-restoring peptide.

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The Effect of Antioxidants on Photoreactivity and Phototoxic Potential of RPE Melanolipofuscin Granules from Human Donors of Different Age

Magdalena M Olchawa, Grzegorz M Szewczyk, Andrzej C Zadlo, Michal W Sarna, Dawid Wnuk, Tadeusz J Sarna

Antioxidants (Basel) . 2020 Oct 26;9(11):E1044. doi: 10.3390/antiox9111044.

Abstract

One of the most prominent age-related changes of retinal pigment epithelium (RPE) is the accumulation of melanolipofuscin granules, which could contribute to oxidative stress in the retina. The purpose of this study was to determine the ability of melanolipofuscin granules from younger and older donors to photogenerate reactive oxygen species, and to examine if natural antioxidants could modify the phototoxic potential of this age pigment. Electron paramagnetic resonance (EPR) oximetry, EPR-spin trapping, and time-resolved detection of near-infrared phosphorescence were employed for measuring photogeneration of superoxide anion and singlet oxygen by melanolipofuscin isolated from younger and older human donors. Phototoxicity mediated by internalized melanolipofuscin granules with and without supplementation with zeaxanthin and α-tocopherol was analyzed in ARPE-19 cells by determining cell survival, oxidation of cellular proteins, organization of the cell cytoskeleton, and the cell specific phagocytic activity. Supplementation with antioxidants reduced aerobic photoreactivity and phototoxicity of melanolipofuscin granules. The effect was particularly noticeable for melanolipofuscin mediated inhibition of the cell phagocytic activity. Antioxidants decreased the extent of melanolipofuscin-dependent oxidation of cellular proteins and disruption of the cell cytoskeleton. Although melanolipofuscin might be involved in chronic phototoxicity of the aging RPE, natural antioxidants could partially ameliorate these harmful effects.

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