Lipophilic Vitamin E Diffusion through Bicontinuous Microemulsions

Dai Kato, Johtaro Yamamoto, Yoshio Suzuki, Tomoyuki Kamata, Hinako Hashimoto, Masashi Kunitake

Anal Chem . 2021 Oct 13. doi: 10.1021/acs.analchem.1c03174. Online ahead of print.

Abstract

We studied the diffusion properties of lipophilic vitamin E (VE) through bicontinuous microemulsions (BME) using both electrochemical and fluorescence correlation spectroscopy (FCS) measurements. We investigated the effect of different composition ratios of micro-water and micro-oil phases in BMEs (W/O_BME). When we employed the BME with a lower W/O_BME value of 40/60 (oil-rich BME) as an electrolyte solution, we obtained a larger current response from VE at a fluorinated nanocarbon film electrode. Further voltammetric studies revealed that a higher VE diffusion coefficient was observed in the oil-rich BME. The FCS results also exhibited faster diffusion through the oil-rich BME, which played a significant role in accelerating the VE diffusion probably due to the widening of the micro-oil phase pathway in the BME. Moreover, the effect of increasing the VE diffusion was pronounced at the interface between the electrode surface and the BME solution. These results indicate that controlling the conditions of the BME as the measurement electrolyte is very effective for achieving superior electrochemical measurements in a BME.

Atsuki Suzuki, Yasuomi Urano, Tomohisa Ishida, Noriko Noguchi

Free Radic Biol Med . 2021 Oct 12;176:356-365. doi: 10.1016/j.freeradbiomed.2021.10.008. Online ahead of print.

Abstract

24(S)-Hydroxycholesterol (24S-OHC) and 25-hydroxycholesterol (25-OHC) are produced by cholesterol 24-hydroxylase and cholesterol 25-hydroxylase, respectively. The purpose of the present study was to determine the type of cell death induced by these oxysterols in neuronal cells, hepatic cells, and keratinocytes, and to elucidate the inhibitory effect of vitamin E homologues on various types of cell death. In human neuronal cells (SH-SY5Y cells), 24S-OHC and 25-OHC caused a cell death that was independent of caspase activation. We reported previously that the esterification of 24S-OHC by acyl-CoA:cholesterol acyltransferase 1 (ACAT1) and the resulting formation of a lipid droplet (LD)-like structure are responsible for the 24S-OHC-induced neuronal cell death. Here, we found that 25-OHC also induced ACAT1-mediated 25-OHC esterification and LD formation in neuronal cells. 25-OHC-induced cell death was inhibited by α-tocopherol (α-Toc) but not by α-tocotrienol (α-Toc3), as observed for 24S-OHC-induced cell death in SH-SY5Y cells. In human hepatic cells (HepG2 cells), these oxysterols caused a cell death that was caspase- and oxysterol-esterification-independent. This cell death was suppressed by both α-Toc and α-Toc3, suggesting the involvement of free-radical-mediated lipid peroxidation in the cell death induced by these oxysterols in hepatic cells. In human keratinocytes (HaCaT cells), these oxysterols caused a caspase-dependent but oxysterol-esterification-independent cell death that was inhibited by α-Toc but not by α-Toc3. These results suggest that α-Toc and α-Toc3 act as radical-scavenging antioxidants against oxysterol-induced cell death in the same way in hepatic cells, whereas their behavior is different in inhibition of cell death in neuronal cells and keratinocytes. Collectively, these results demonstrated that 24S-OHC and 25-OHC induced the same type of cell death in each of the cell types examined, and that α-Toc and α-Toc3 exerted different effects, depending on the type of cell death.

Soudabeh Sabetian, Bahia Namavar Jahromi, Sina Vakili, Sedighe Forouhari, Shohreh Alipour

Biomed Res Int . 2021 Oct 11;2021:5588275. doi: 10.1155/2021/5588275. eCollection 2021.

Abstract

Background: Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate.

Methods: After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups.

Results: There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks.

Conclusion: Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two-arm, blinded, randomized, placebo-controlled clinical trial (IRCTID: IRCT2014020616506N1, 2014-03-18).

Ammu K Radhakrishnan, Jeya Seela Anandha Rao, Shonia Subramaniam, Premdass Ramdas

Curr Res Immunol . 2021 Oct 9;2:169-174. doi: 10.1016/j.crimmu.2021.10.001. eCollection 2021

Abstract

DNA methylation plays a crucial role in polarising naïve lymphocytes towards their various sub-populations to fight against many immune challenges including establishment of tumour. Gamma-tocotrienol (γT3) is a natural form of vitamin E, reported to possess anticancer and immunomodulatory effects. This study reports the anticancer effects of γT3 through modulation of DNA methylation in several genes in CD4⁺ T-lymphocytes using a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with γT3 or vehicle (soy oil) for two-weeks via oral gavage before they were inoculated with 4T1 mouse mammary cancer cells. Supplementation continued until the mice were sacrificed. At autopsy, blood was collected via cardiac puncture and CD4⁺ T-cells were isolated for DNA extraction. The DNA was analysed using the EpiTech Methyl II mouse T-helper cell differentiation PCR array. γT3 supplementation reduced tumour growth in the tumour-induced animals and modulated host immune system by inducing changes in DNA methylation patterns of the HOXA10, IRF4 and RORα genes, which are involved in differentiation and clonal expansion of CD4⁺ T-cells. Results suggest that γT3 may enhance cell-mediated immune response in mice with breast cancer by inducing changes in DNA methylation pattern.

Zhen-Qi Yu, Lan-Min Wang, Wan-Xi Yang

Gene . 2021 Oct 7;808:145998. doi: 10.1016/j.gene.2021.145998. Online ahead of print.

Abstract

In tumour cells, vitamin E and its derivatives play a critical role in the regulation of multiple signalling pathways through their oxidative and nonoxidative functions. To date, there are 8 known natural vitamin E forms and many kinds of derivatives, among which VES and α-TEA have excellent anticancer activities. The MAPK pathway consists of a complex cascade of proteins that control the proliferation, differentiation and apoptosis of tumour cells. The MAPK pathway includes four subfamilies, ERK1/2, JNK1/2, p38 MAPK, and ERK5. Most of the proteins in these subfamilies interact with each other in a complex manner. The anticancer function of vitamin E and its derivatives is closely related to the MAPK cascade. Studies have shown that in tumour cells, α-T/γ-T/γ-T3/δ-T3/VES/α-TEA regulated ERK1/2, prevent tumorigenesis, inhibit tumour cell growth and metastasis and induce cell differentiation, apoptosis, and cell cycle arrest; γ-T3/δ-T3/VES/α-TEA regulates JNK1/2, induce apoptosis, reduce ceramide synthesis and inhibit proliferation; and γ-T3/δ-T3/VES regulate p38 MAPK and induce apoptosis. This paper reviews the role of vitamin E and its derivatives in the MAPK cascade, and tumour cells are used as a model in an attempt to explore the mechanism of their interactions.

Lucía Castro-Vázquez, Virginia Rodríguez-Robledo, María Plaza-Oliver, Manuel J Santander-Ortega, M Victoria Lozano, Joaquín González, Noemí Villaseca, Pilar Marcos, M Mar Arroyo-Jiménez

J Food Sci Technol . 2021 Oct;58(10):4034-4044. doi: 10.1007/s13197-020-04866-9. Epub 2021 Jan 5.

Abstract

The objective of this study was to use accelerated-solvent-extraction to achieve antioxidant extracts from chia seeds oils, enriched in tocopherols and tocotrienols, namely tocochromanols. Nanotechnology applications have been also incorporated to develop an innovative formulation of chia seeds oil nanoemulsion that preserve its antioxidant potential after conditions of oxidative stress. Chia seeds oils proved to be a valuable source of tocochromanols, from 568.84 to 855.98 μg g^-1, depending on the geographical provenance. Quantitative data obtained by LC-DAD-ESI-MS/MS showed outstanding levels of γ-Tocopherol, over 83%, followed far behind by Tocopherols-(α, β, δ) and Tocotrienols-(α, β, δ, γ)-tocotrienols. The characteristic tocochromanols fingerprint of chia seeds oils was positively correlated with the FRAP and DPPH antioxidant activity of the extracts (between 18.81 and 138.48 mg Trolox/g). Formulation of the Chia seeds oils as nanoemulsions did not compromised the antioxidant properties of fresh extracts. Interestingly, nanoemulsions retained about the 80% of the initial antioxidant capacity after UV-induced stress, where the non-emulsified oils displayed a remarkable reduction (50-60%) on its antioxidant capacity under the same conditions. These antioxidant chia seeds formulations can constitute a promising strategy to vectorizing vitamin E isomers, in order to be used for food fortification, natural additives and to increase the self-life of food products during packing.

Daniela Rios , Ana Paula Boteon, Camilla Cristina Lira Di Leone, Tainara Tonon Castelluccio, Fernanda Lyrio Mendonça, Franciny Querobim Ionta, Marília Afonso Rabelo Buzalaf, Thiago Saads Carvalho

J Dent . 2021 Oct;113:103781. doi: 10.1016/j.jdent.2021.103781. Epub 2021 Aug 13.

Abstract

Objectives: This study evaluated the in vitro effect of different components of palm oil on enamel in a short-term erosive challenge.

Methods: The acquired enamel pellicle (AEP) was previously formed in situ for 2 h. Subsequently, the bovine enamel blocks were treated in vitro according to following solutions: G1-palm oil; G2-85% tocotrienol solution; G3-oily vitamin E; G4-oily vitamin A; G5-deionized water (negative control); G6-stannous-containing solution (Elmex® Erosion Protection Dental Rinse) (positive control). After application of the treatment solutions (500 µl, 30 s), the blocks were immersed in 0.5% citric acid (pH 2.4) during 30 s (initial erosion). The response variable was the percentage of surface hardness loss. Data were analyzed by one-way ANOVA and Fisher’s Test (p < 0.05).

Results: The positive control (G6), palm oil (G1) and oily vitamin E (G3) groups presented the lowest percentage of surface hardness loss, and were statistically different from the negative group (G5) (p < 0.05), and no differences were found between these three groups. The 85% tocotrienol solution (G2) and oily vitamin A groups (G4) were not different to the negative control group.

Conclusions: Stannous-containing positive control (Elmex® Erosion Protection), palm oil and oily Vitamin E were able to protect enamel against the erosive challenge performed in this in vitro study. In addition, vitamin E is probably the key ingredient of palm oil responsible for preventing enamel erosion.

Clinical significance: Vitamin E presented similar preventive effect to a commercial mouthwash stannous-containing solution (Elmex® Erosion Protection) against initial erosion and, it can be considered as a promising natural alternative for the formulations of solutions aiming to prevent erosive tooth wear.

Fereidoon Shahidi, Ana Clara C Pinaffi-Langley, Jocelyn Fuentes, Hernán Speisky, Adriano Costa de Camargo

Free Radic Biol Med . 2021 Oct 2;176:312-321. doi: 10.1016/j.freeradbiomed.2021.09.025. Online ahead of print.

Abstract

Vitamin E comprises a group of vitamers that includes tocopherols and tocotrienols. They occur in four homologues according to the number and position of methyl groups attached to the chromanol ring. Vitamin E, a liposoluble antioxidant, may participate as an adjuvant in the prevention and treatment of cardiovascular, neurological, and aging-related diseases. Furthermore, vitamin E has applications in the food industry as a natural additive. In this contribution, the most recent information on the dietary sources of vitamin E, including common, novel, and unexplored sources, is presented. Common edible oils, such as those of corn, olive, palm, rice bran, and peanut, represent the most prominent sources of vitamin E. However, specialty and underutilized oils such as those obtained from tree nuts, fruit seeds, and by-products, emerge as novel sources of this important micronutrient. Complementary studies should examine the tocotrienol content of vitamin E dietary sources to better understand the different biological functions of these vitamers.

Nurul Alimah Abdul Nasir, Muhammad Zulfiqah Sadikan, Renu Agarwal

Asia Pac J Clin Nutr . 2021 Sep;30(3):537-555. doi: 10.6133/apjcn.202109_30(3).0020.

Abstract

Tocotrienols have been reported to exert anticancer, anti-inflammatory, antioxidant, cardio-protective and boneprotective effects through modulation of NFκB signalling pathway. The objective of this systematic review is to evaluate available literature showing the effect of tocotrienols on NFκB signalling pathway and identify the potential mechanisms involved. A comprehensive search was conducted using PubMed and SCOPUS databases using the keywords “tocotrienol” and “NFκB” or “nuclear factor kappa b”. Main inclusion criteria were English language original articles showing the effect of tocotrienol on NFκB signalling pathway. Fifty-nine articles were selected from the total of 117 articles initially retrieved from the literature search. Modulation of regulatory proteins and genes such as inhibition of farnesyl prenyl transferase were found to be the mechanisms underlying the tocotrienol-induced suppression of NFκB activation.

Sookyoung Jeon, Qiyao Li, Katherine M Ranard, Stanislav S Rubakhin, Jonathan V Sweedler, Matthew J Kuchan, John W Erdman

Nutr Res . 2021 Sep;93:79-86. doi: 10.1016/j.nutres.2021.07.005. Epub 2021 Jul 25.

Abstract

Natural (RRR-) α-tocopherol (αT) is more bioactive than synthetic (all racemic, all rac-) αT, but not enough is known about the tissue kinetics of the 2 αT sources. We examined the time-course bioaccumulation of natural versus synthetic αT in tissues of young, marginally vitamin E-deficient mice using ¹³C-RRR-αT or ¹³C-all rac-αT tracers. In experiment 1, 3-week old male wild-type mice were fed a vitamin E-deficient diet for 0, 1, 2, or 3 weeks (n = 5/time point). Tissue αT levels were analyzed by HPLC-PDA. Feeding a vitamin E-deficient diet for up to 3 weeks decreased total αT concentrations in all analyzed tissues except the brain, which maintained its αT level. In experiment 2, a 2-week αT-depletion period was followed by administration of a single oral dose of 0.5 mg of ¹³C-RRR-αT or ¹³C-all rac-αT. At 12 hr, 1, 2, and 4 days post-dose, serum and multiple tissues were collected (n = 3/time point). αT was quantified by HPLC-PDA, and ¹³C-αT enrichment was determined by LC-MS. Both sources of ¹³C-αT reached maximum serum levels at 12 hr post-dose. ¹³C-RRR-αT levels were significantly higher than ¹³C-all rac-αT in serum at 1 d post-dose, and in heart, lungs, and kidney at 2d post-dose. In brain, ¹³C-RRR-αT concentrations were significantly higher than ¹³C-all rac-αT at 2 and 4 d post-dose. At 4 d post-dose, ¹³C-αT levels were similar between the 2 sources in examined tissues except for brain and adipose tissue where ¹³C-RRR-αT was higher. In conclusion, αT bioaccumulation over time varied substantially depending on αT source and tissue type.