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.


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.


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.


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.


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.


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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Vitamin C and vitamin C plus E improve the immune function in the elderly

Mónica De la Fuente, Carmen Sánchez, Carmen Vellejo, Estefanía Díaz-Del Cerro, Francisco Arnalich, Ángel Hernanz

Exp Gerontol . 2020 Oct 19;111118. doi: 10.1016/j.exger.2020.111118. Online ahead of print.


With aging the immune response is impaired. This immunosenescence, in which an alteration of the redox state of the immune cells appears, is involved in the rate of aging. Since leukocyte function is a good marker of health and predictor of longevity, the effects of daily oral administration of the antioxidant vitamin C (500 mg), or both vitamin C (500 mg) and vitamin E (200 mg) on several blood neutrophil (adherence, chemotaxis, phagocytosis, and superoxide anion levels) and lymphocyte (adherence, chemotaxis, proliferation, interleukin-2 secretion and natural killer activity) functions were studied in healthy elderly men and women. These parameters were analysed before supplementation, after 3 months of supplementation, and 6 months after the end of supplementation. The results showed that vitamin C, in elderly participants, improved the immune functions studied which achieved values close to those of young adults. These effects were maintained in several functions after 6 months without supplementation. Similar effects were found in the elderly supplemented with both vitamin C and E. Thus, a short period of vitamin C or vitamin C and E ingestion, with the doses used, improves the immune function in elderly men and women and could contribute to a healthy longevity.

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The beneficial effects of antioxidants combination on cardiac injury induced by tetrachloromethane

Aliah R Alshanwani, Laila M Faddah, Hanan Hagar, Ahlam M Alhusaini, Sameerah Shaheen, Raeesa A Mohammad, Fatima M B Alharbi, Alaa AlHarthii, Amira M Badr

Drug Chem Toxicol . 2020 Oct 15;1-9. doi: 10.1080/01480545.2020.1831012. Online ahead of print.


The purpose of this research was to evaluate the efficacy of carsil (CAR) either alone or in combination with α-tocopherol (α-TOCO) and/or turmeric (TUMR) against tetrachloromethane (TCM)-induced cardiomyocyte injury in rats. Administration of CAR either alone or in combination with α-TOCO and/or TUMR post-TCM injection, significantly mitigated the increases in serum troponin T, creatine kinase-MB (CK-MB) as well as interleukin-6 (IL-6), interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP). They also decline the elevation of caspase-3, vascular endothelial growth factor (VEGF) protein expression as well as DNA damage in cardiac tissues induced by TCM. The biochemical results were confirmed by histopathological investigation. Conclusion: The combination of the three antioxidants showed greater cardioprotective potential, compared to individual drugs. Therefore, this combination may be recommended as a complementary therapy to antagonize cardiac injury induced by different insults.

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Effect of Vitamin E on Cisplatin-induced Memory Impairment in Male Rats

Masoud Hosseinzadeh, Amir Alizadeh, Parnian Heydari, Marzieh Kafami, Mahmoud Hosseini, Farimah Beheshti, Narges Marefati, Moustafa Ghanbarabadi

Acta Neuropsychiatr . 2020 Oct 15;1-16. doi: 10.1017/neu.2020.34. Online ahead of print.


Objective: Neurotoxicity is an adverse effect caused by cisplatin due to inflammation and oxidative stress in the central nervous system. The present study aimed to assess the effects of vitamin E injection on the learning and memory of rats with cisplatin-induced cognitive impairment.

Methods: Male rats were administered with cisplatin (2 mg/kg/7day ; i.p.) and/or vitamin E (200 mg/kg/7 day; i.p.) for one week, and the control group received saline solution. Spatial memory was evaluated using Morris water maze (MWM). In addition, the hippocampal concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical methods.

Results: According to the findings, cisplatin significantly increased the escape latency, while decreasing the time spent and traveled pathway in the target quadrant on the final trial day compared to the control group. Furthermore, pretreatment with vitamin E significantly reversed all the results in the spatial memory test. The biochemical data indicated that vitamin E could decrease MDA activity and increase thiol and SOD activity compared to the control group.

Conclusion: According to the results, vitamin E could improve cisplatin-induced memory impairment possibly through affecting the hippocampal oxidative status.

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Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD

Antonella Mosca, Annalisa Crudele, Antonella Smeriglio, Maria Rita Braghini, Nadia Panera, Donatella Comparcola, Arianna Alterio, Maria Rita Sartorelli, Giulia Tozzi, Massimiliano Raponi, Domenico Trombetta, Anna Alisi

Dig Liver Dis . 2020 Oct 12;S1590-8658(20)30920-8. doi: 10.1016/j.dld.2020.09.021. Online ahead of print.


Background: The rise in paediatric non-alcoholic fatty liver disease (NAFLD) is particularly alarming. We recently reported that Hydroxytyrosol (HXT) and Vitamin E (VitE) may improve oxidative stress, insulin resistance, and steatosis in children with biopsy-proven NAFLD.

Aim: Here, we investigated if HXT+VitE may reduce systemic inflammation in the above-mentioned patients.

Methods: This study analysed the plasma levels of IL (interleukin)-6, IL-1β, IL-10, tumour necrosis factor (TNF)-α, 4‑hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2’deoxyguanosine (8-OHdG) in children enrolled in the HXT+VitE trial (ClinicalTrials.gov, NCT02842567).

Results: Changes in markers of systemic inflammation were found in both placebo (Pla) and HXT+VitE. In particular, after four months, the levels of IL-1β and TNF-α were reduced in both groups, while IL-6 decreased, and IL-10 increased significantly only in the group treated with HXT+VitE. Children treated with HXT+VitE showed a significant decrease of 4-HNE and 8-OHdG that correlated with the improvement of triglyceride levels. Noticeably, only the 8-OHdG decrease correlated with steatosis amelioration and with the increase of IL-10 levels.

Conclusion: The treatment with HXT and VitE reduced the NAFLD-related systemic inflammation in children, mainly by an increase of IL-10 circulating levels that occurred in response to DNA damage recovery, ultimately improving steatosis and hypertriglyceridemia.

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The effect of vitamin E and selenium combination in repairing fluoride-induced DNA damage to NRK-52E cells

Veysel Yüksek, Sedat Çetin, Ayşe Usta

Mol Biol Rep . 2020 Oct;47(10):7761-7770. doi: 10.1007/s11033-020-05852-2. Epub 2020 Oct 6.


Prolonged and excessive fluoride exposure can lead to fluorosis. The kidney is one of the organs that are injured mostly due to fluoride-induced damage. Fluoride can induce DNA damage at cytotoxic concentrations. This study aims to determine the extent of NaF-induced DNA damage and to investigate the effect of vitamin E and selenium combination (ES) in preventing and repairing this damage. For this purpose, we administered different combinations of NaF and ES to NRK-52E cells and determined the effective concentrations of ES and the NaF IC50 values associated with different incubation times (3, 12, and 24 h) by using the MTT assay. The determined quantities of NaF IC50 in association with time and the NaF IC50 + ES combination were administered to the cells. The extent of DNA damage was determined with the comet assay and the expression levels of the Ku70/80 and PARP-1 genes were determined with the RT-qPCR method. DNA damage significantly increased in all experimental groups compared to the control group (p < 0.05). It was found out that the NaF and ES combination statistically reduced the DNA damage compared to the damage observed in the NaF-treated groups (p < 0.05). Treatment of the ES combination significantly increased the expressions of Ku70 and Ku80 genes involved in DNA repair (p < 0.05). We concluded that vitamin E and selenium can potentially be effective in the repair of fluoride-induced DNA damage based on the results of this in vitro study. Our results may shed light on the prevention of DNA damage associated with fluorosis.

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