Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements

Tadokoro K, Ohta Y, Inufusa H, Loon AFN, Abe K

Int J Mol Sci. 2020 Mar 13;21(6). pii: E1974. doi: 10.3390/ijms21061974.

Abstract

Oxidative stress plays a crucial role in Alzheimer’s disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the Aβ cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.

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The effect of vitamin E and C on comet assay indices and apoptosis in power plant workers: A double blind randomized controlled clinical trial

Bagheri Hosseinabadi M, Khanjani N, Atashi A, Norouzi P, Mirbadie SR, Mirzaii M

Mutat Res. 2020 Feb - Mar;850-851:503150. doi: 10.1016/j.mrgentox.2020.503150. Epub 2020 Feb 4.

Abstract

Extremely low frequency electromagnetic fields have been classified as a possible human carcinogen by the International Agency for Research on Cancer and this has raised some concern about its health effects on employees extensively exposed to these fields at thermal power plants. In this study, the effect of using vitamin E and C supplements have been examined on employees working at a thermal power plant. In this randomized controlled, double-blind clinical trial, 81 employees from different parts of the thermal power plant were enrolled between July and November 2017, and divided into four groups: Group 1 received vitamin E (400 units/day), Group 2: vitamin C (1000 mg/day), Group 3: vitamin E + C and Group 4: no intervention. DNA damage was measured in peripheral blood lymphocytes using comet assay and apoptosis, using flow cytometry. Based on the results, tail intensity and tail length in the vitamin E group, and all comet assay indices in the vitamin E + C and vitamin C groups (except DNA damage index) significantly decreased after the intervention, while the comet assay indices did not change significantly in the control group. None of the flow cytometry indices including early apoptosis, late apoptosis and necrosis changed after intervention in either group. The use of antioxidant vitamins such as E and C, can increase the activity of the non-enzymatic antioxidant defense system, and protect DNA from damage caused by exposure to extremely low frequency magnetic fields. But, taking these vitamins has no effect on apoptosis. It seems that consumption of vitamin E affected all investigated comet assay indices and can be probably considered as the best intervention.

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Study of subcellular localization of Glycine max γ-tocopherol methyl transferase isoforms in N. benthamiana

Kumari K, Rai MP, Bansal N, Prashat GR, Kumari S, Srivathsa R, Dahuja A, Sachdev A, Praveen S, Vinutha T

3 Biotech. 2020 Mar;10(3):110. doi: 10.1007/s13205-020-2086-9. Epub 2020 Feb 11.

Abstract

Gamma-tocopherol methyltransferase (γ-TMT) converts γ-toc to α-toc-the rate limiting step in toc biosynthesis. Sequencing results revealed that the coding regions of γ-TMT1 and γ-TMT3 were strongly similar to each other (93% at amino acid level). Based on the differences in the N-terminal amino acids, Glycine maxγ-TMT proteins are categorized into three isoforms: γ-TMT1, 2 and 3. In silico structural analysis revealed the presence of chloroplast transit peptide (cTP) in γ-TMT1 and γ-TMT3 protein. However, other properties of transit peptide like presence of hydrophobic amino acids at the first three positions of N-terminal end and lower level of acidic amino acids were revealed only in γ-TMT3 protein. Subcellular localization of GFP fused γ-TMT1 and γ-TMT3 under 35S promoter was studied in Nicotiana benthamiana using confocal microscopy. Results showed that γ-TMT1 was found in the cytosol and γ-TMT3 was found to be localized both in cytosol and chloroplast. Further the presence γ-TMT3 in chloroplast was validated by quantifying α-tocopherol through UPLC. Thus the present study of cytosolic localization of the both γ-TMT1 and γ-TMT3 proteins and chloroplastic localization of γ-TMT3 will help to reveal the importance of γ-TMT encoded α-toc in protecting both chloroplastic and cell membrane from plant oxidative stress.

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The inhibitor-evoked shortage of tocopherol and plastoquinol is compensated by other antioxidant mechanisms in Chlamydomonas reinhardtii exposed to toxic concentrations of cadmium and chromium ions

Nowicka B, Fesenko T, Walczak J, Kruk J

Ecotoxicol Environ Saf. 2020 Mar 15;191:110241. doi: 10.1016/j.ecoenv.2020.110241. Epub 2020 Jan 31.

Abstract

One of the major mechanisms of heavy metal toxicity is the induction of oxidative stress. Redox-active heavy metals, like chromium, can induce it directly, whereas redox-inactive metals, like cadmium, play an indirect role in the generation of reactive oxygen species (ROS). Living organisms defend themselves against oxidative stress taking advantage of low-molecular-weight antioxidants and ROS-detoxifying enzymes. Tocopherols and plastoquinol are important plastid prenyllipid antioxidants, playing a role during acclimation of Chlamydomonas reinhardtii to heavy metal-induced stress. However, partial inhibition of synthesis of these prenyllipids by pyrazolate did not decrease the tolerance of C. reinhardtii to Cr- and Cd-induced stress, suggesting redundancy between antioxidant mechanisms. To verify this hypothesis we have performed comparative analyses of growth, photosynthetic pigments, low-molecular-weight antioxidants (tocopherols, plastoquinol, plastochromanol, ascorbate, soluble thiols, proline), activities of the ascorbate peroxidase (APX), catalase and superoxide dismutase (SOD) and cumulative superoxide production in C. reinhardtii exposed to Cd2+ and Cr2O72- ions in the presence or absence of pyrazolate. The decreased α-tocopherol and plastoquinol content resulted in the increase in superoxide generation and APX activity in pyrazolate-treated algae. The application of heavy metal ions and pyrazolate had a pronounced impact on Asc and total thiol content, as well as SOD and APX activities (the latter only in Cd-exposed cultures), when compared with algae grown in the presence of heavy metal ions or pyrazolate alone. The superoxide production in cultures exposed to heavy metal ions and pyrazolate decreased when compared to the cultures exposed to either heavy metal ions or an inhibitor alone.

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Vitamins combined with traditional Chinese medicine for male infertility: A systematic review and meta-analysis

Wang M, Wang Q, Du Y, Jiang H, Zhang X

Andrology. 2020 Mar 14. doi: 10.1111/andr.12787. [Epub ahead of print]

Abstract

BACKGROUND:

Male infertility is a tough problem in medicine. This article aims to provide the latest evidence for the efficacy and safety of traditional Chinese medicine (TCM) combined with vitamins in the treatment of male infertility.

METHOD:

All randomized controlled trials (RCTs) that used TCM combined with vitamins for male infertility treatment were included in databases of China National Knowledge Infrastructure (CNKI), Wanfang, VIP Database, China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library. The quality of the included articles was evaluated using the Cochrane Reviewer’s Handbook 5.3, and meta-analysis was performed using Stata 15.

RESULTS:

A total of 14 eligible studies with 1488 patients were included in this meta-analysis. The results suggested that, compared with vitamin E or vitamin E + C alone, combination of TCM with vitamins increased significantly sperm concentration, sperm motility, sperm viability, liquefaction time of semen, the activity of acrosome enzyme, and the pregnancy rate of patients with male infertility. Three kinds of TCM (Shengjing capsule, Huanshao capsule, and compound Xuanju capsule) showed significant improvement for male infertility in terms of pregnancy rate, sperm concentration, or sperm motility. In addition, the results of the publication bias test demonstrated that no significant bias occurred.

CONCLUSION:

Traditional Chinese medicine combined with vitamins has significant efficacy in the treatment of male infertility with no increase in side effects. The specific implementing regulations still need more long-term, multicenter, randomized, and double-blind clinical trials.

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Preparation and Optimization of In Situ Gel Loaded with Rosuvastatin-Ellagic Acid Nanotransfersomes to Enhance the Anti-Proliferative Activity

Hosny KM, Rizg WY, Khallaf RA

Pharmaceutics. 2020 Mar 13;12(3). pii: E263. doi: 10.3390/pharmaceutics12030263.

Abstract

The objective of this study was to develop an optimized sustained-release nanotransfersomes (NTS) based in situ gel formulation of rosuvastatin (RO) combined with ellagic acid (EA) antioxidant, to enhance cytotoxic and anti-proliferative activity against tongue carcinoma. The concentrations of lecithin, Tween 80, and d-tocopherol polyethylene glycol succinate (TPGS) were considered as independent variables. Particle size, entrapment, and stability were selected as dependent variables. The obtained formulation containing 25% lecithin, 20% Tween 80, and TPGS 15% fulfilled the prerequisites of the optimum formulation. RO-NTS loaded in situ gel was prepared and optimized for concentrations of Poloxamer 407, and Carbopol, using statistical design. Drug release from in situ gel showed a sustained release profile. The RO IC50 was decreased by half for the in situ gel in comparison to plain RO and RO-EA-NTS. A significant amount of caspase-3 was detected in all the formulation treatments. The studies indicated that EA’s synergistic anti-oxidant effect owing to a high affinity to the PGP efflux transporter and higher penetration in the RO-NTS formulation led to a higher inhibition against human chondrosarcome-3 cancer cell lines. RO-EA NTS-loaded in situ gel had a sustained release that could be significant in localized therapy as an alternative to surgery in the treatment of aggressive tongue carcinoma.

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The effect of β-carotene on the mortality of male smokers is modified by smoking and by vitamins C and E: evidence against a uniform effect of nutrient

Hemilä H

J Nutr Sci. 2020 Mar 11;9:e11. doi: 10.1017/jns.2020.3.

Abstract

A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found that β-carotene supplementation increased the risk of pneumonia 4-fold in those who started smoking at the age of ≥21 years and smoked ≥21 cigarettes/d (a subgroup of 7 % of the study population). The present study hypothesised that β-carotene increases mortality in the same subgroup. The ATBC Study (1985-1993) recruited 29 133 Finnish male smokers (≥5 cigarettes/d) aged 50-69 years. Cox regression models were constructed to estimate the effect of β-carotene supplementation in subgroups. β-Carotene increased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at ≥21 years and smoked ≥21 cigarettes/d. Within this subgroup, there was strong evidence of further heterogeneity. The effect of β-carotene supplementation was further modified by dietary vitamin C intake, fruit and vegetable intake (P = 0·0004), and by vitamin E supplementation (P = 0·011). Thus, harm from β-carotene was not uniform within the study population. Interactions between β-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not be extrapolated to the general population. Heterogeneity of the β-carotene effect on mortality challenges the validity of previous meta-analyses that have pooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants and all people.

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Retinol and α-tocopherol in pregnancy: Establishment of reference intervals and associations with CBC

Liu J, Zhan S, Jia Y, Li Y, Liu Y, Dong Y, Tang G, Li L, Zhai Y, Cao Z

Matern Child Nutr. 2020 Mar 5:e12975. doi: 10.1111/mcn.12975. [Epub ahead of print]

Abstract

Profound physiological changes during pregnancy may affect the requirement of retinol and tocopherol, which are essential micronutrients for the maintenance of maternal health and foetal development. However, the current reference intervals (RIs) of retinol and tocopherol are based on non-pregnant population. In the present study, a liquid chromatography-tandem mass spectrometry quantitation method for serum retinol and α-tocopherol was established and validated. In addition, we established trimester-specific RIs of retinol and α-tocopherol using the data from paired screening test for 31,301 outpatients who participated in the prenatal vitamins A/E evaluation program at our hospital using the Hoffmann method, which is a simple indirect RI estimation method that does not require the recruitment of healthy subjects. Further, to explore the associations between the levels of retinol and α-tocopherol and the parameters of complete blood count (CBC), the results of retinol, α-tocopherol, and CBC of 1,977 pregnant outpatients in the third trimester were analysed. The testing interval between the levels of vitamins and CBC was no more than 7 days. Although no significant changes were noticed in the levels of retinol, the α-tocopherol levels continuously increased with normal physiological changes throughout pregnancy. Lower retinol levels were associated with the higher incidence of anaemia, whereas higher levels of retinol and lower levels of α-tocopherol were associated with higher platelet count.

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Role of α-tocopherol and Lactobacillus plantarum in the alleviation of mercuric chloride-induced testicular atrophy in rat’s model: Implication of molecular mechanisms

Fadda LM, Alhusaini AM, Al-Qahtani QH, Ali HM, Hasan IH

J Biochem Mol Toxicol. 2020 Mar 5:e22481. doi: 10.1002/jbt.22481. [Epub ahead of print]

Abstract

The present work was aimed to evaluate the protective effects of alpha-tocopherol (α-toco) and/or Lactobacillus plantarum (LCB) against testicular atrophy induced by mercuric chloride (MCH). Rats were injected with 5 mg/kg MCH for 5 days consecutively, then treated with 100 mg/kg α-toco and 6 × 1010 CFU 1.8701/kg LCB alone or together for 3 weeks. The MCH elevated serum TNF-α, IL- 6, caspase-3, and testicular malondialdehyde. However, serum testosterone, dehydroepiandrosterone, testicular messenger RNA of a steroidogenic acute regulatory protein, 17-β-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, glutathione level, and superoxide dismutase activity were decreased. Protein expression of Nrf2 was downregulated whereas that of Bax and DNA fragmentation was upregulated in the testicular tissues. Treatment with α-toco and LCB ameliorated the deviated biochemical parameters and improved tissue injury. It was concluded that the combination of LCB and α-toco achieved promising results in the amelioration of MCH-induced testicular atrophy. Nrf2, Bax expressions, and DNA fragmentation are involved in the testicular atrophy induced by MCH.

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Fatty acids based α-Tocopherol loaded nanostructured lipid carrier gel: In vitro and in vivo evaluation for moisturizing and anti-aging effects

Ijaz M, Akhtar N

J Cosmet Dermatol. 2020 Mar 4. doi: 10.1111/jocd.13346. [Epub ahead of print]

Abstract

BACKGROUND:

α-Tocopherol is a potent antioxidant present in the skin. Its concentration decreases with age. Synthetically available α-tocopherol is viscous, irritating to skin and unstable toward oxidation and ultraviolet (UV) light.

AIMS:

To develop fatty acids based nanostructured lipid carrier (NLC) gel loaded with α-tocopherol and to evaluate its moisturizing and anti-aging properties.

METHODS:

Lauric acid, oleic acid, and Tween-80 were used as solid lipid, liquid lipid, and surfactant, respectively. Seven formulations (F0-F6) were developed by using different concentration of ingredients. Most optimized formulation (F2) was selected for further study on the basis of characterization. Dialysis tube method was used for release study. F2 was incorporated in gel, and then, in vitro and noninvasive in vivo study regarding skin moisture content by corneometer® and skin mechanical properties by cutometer® for 12 weeks on human volunteers (n = 13) was conducted.

RESULTS:

Size, polydispersibility index (PDI), zeta potential, and %entrapment efficiency (%EE) of optimized formulation (F2) were found 82 nm, 0.261, -28.6, and 94.88 ± 1.16, respectively. Particles were spherical in shape. The release profile showed initial burst and then sustained release, and release data were best fitted to weibull model. α-tocopherol loaded NLC gel (NLCG) appeared physically stable for 12 weeks at room temperature and showed significant results in terms of skin capacitance and mechanical properties. Rheological assessment showed non-Newtonian behavior.

CONCLUSION:

Fatty acids based NLC proved to be a promising carrier of photochemically unstable lipophilic vitamin E with enhanced moisturizing and anti-aging properties.

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