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.

Mussarat Ashraf, Fatima Mustansir, Syed Mujtaba Baqir, Faiza Alam, Rehana Rehman

J Pak Med Assoc . 2020 Oct;70(10):1762-1766. doi: 10.5455/JPMA.40329.

Abstract

Objective: To study the impact of Vitamin E (VE) levels of follicular fluid (FF) on oocyte competence, embryo development and pregnancy outcome in patients after intra cytoplasmic sperm injection (ICSI).

Methods: It was a cross-sectional study conducted in Islamabad Clinic Serving Infertile Couples in which follicular fluid of 137 females booked for ICSI, was obtained during oocyte retrieval, centrifuged and stored for analysis. VE levels in FF were analyzed by enzyme linked immune sorbent assay. Receiver Operating Curve (ROC)was used to demarcate VE levels required for acquiring pregnancy. Generalized linear model using log binomial regression was applied to see the effect of VE on pregnancy, the effect of VE on oocyte and embryo parameters was assessed by linear regression; all p-values less than 0.05 were considered statistically significant.

Results: ROC suggested 5.49 (unit) as the cutoff value of VE in the pregnancy group, with 72.9% area under the curve. Ninety-one females comprised Group I with VE > 5.49, whereas forty six females formed Group II with VE < 5.49. Follicular fluid VE levels were significantly high in 39 (28.5%) females who compromised pregnancy group. Chances of pregnancy increased to 4% with an increase in VE levels (p-value 0.01). VE gave significant positive relationship with all oocyte (retrieved, mature and fertilized) parameters, cleavage of embryo till its differentiation to blastocysts (p<0.01).

Conclusions: Adequate amount of VE in follicular fluid enhances the possibility of maturation of oocytes which resulted in better reproductive outcome after ICSI.

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.

Ki-Hong Hong, Young Lee

J Inflamm Res . 2020 Oct 29;13:799-811. doi: 10.2147/JIR.S265856. eCollection 2020.

Abstract

Purpose: Vitamins exert its effect through different isoforms. The isoform conversion phases involved are affected outside factors. Here, we investigated the correlation between serum retinol, α-tocopherol, and serum inflammatory markers using stratified data acquired from 2016 to 2018 Korea National Health and Nutrition Examination Survey (KNHANES).

Materials and methods: This study was based on data acquired from the 7th edition (2016-2018) of the Korea National Health and Nutrition Examination Survey, consisting of survey data on smoking and alcohol drinking, serum retinol level, serum α-tocopherol level, high-sensitivity C-reactive protein (hs-CRP), and baseline characteristics.

Results: There was a negative correlation between serum retinol and hs-CRP in alcohol drinking men. There was a negative correlation between serum retinol and hs-CRP in the alcohol-nonsmoking female group. There was a positive correlation between α-tocopherol and hs-CRP in the nonsmoking and alcohol-drinking group. There was a positive correlation between α-tocopherol and hs-CRP in the nonsmoking and alcohol-drinking female group. There was positive correlation between vitamin A and E and metabolic syndrome. The lowest vitamin A level was observed in subjects with all five metabolic syndrome criteria matched.

Conclusion: There was a negative correlation between serum retinol and hs-CRP and positive correlation between α-tocopherol and hs-CRP. Absorption and secretion of serum retinol are affected by inflammation status through retinol-binding protein. Alcohol acts as a competitive inhibitor of vitamin A oxidation through alcohol dehydrogenase and ALDH activity. Smoking causes inflammation and induces reactive oxygen species scavenging system and increases cytochrome p450 levels. These factors may have contributed to the observed findings. Metabolic syndrome subjects increased as the levels of vitamin A and vitamin E increased. Since obesity is inversely related to ALDH activity, we postulate that patients with metabolic syndrome may also have low ALDH activity, especially in the Asian population. Future studies are warranted to study the efficacy of ALDH or ALDH inducers in patients with vitamin A deficiency or metabolic syndrome.

Hong Chuan Loh, Renly Lim, Kai Wei Lee, Chin Yik Ooi, Deik Roy Chuan, Irene Looi, Yuen Kah Hay, Nurzalina Abdul Karim Khan

Stroke Vasc Neurol . 2020 Oct 27;svn-2020-000519. doi: 10.1136/svn-2020-00051

Abstract

There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92-1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77-1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88-1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85-0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98-1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.

Chiman Salehi, Monireh Seiiedy, Hamid Soraya, Farzaneh Fazli, Morteza Ghasemnejad-Berenji

Naunyn Schmiedebergs Arch Pharmacol . 2020 Oct 27. doi: 10.1007/s00210-020-02007-9. Online ahead of print.

Abstract

Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in the hippocampus, leading to severe impairment in behavior, learning, and memory functions. This study aimed to evaluate the neuroprotective effects of bisoprolol (biso) and vitamin E (vit E) treatment alone or in combination on cerebral ischemia/reperfusion (I/R) injury. A total of 30 male rats were divided randomly into five groups (n = 6), sham, I/R, I/R + biso, I/R + vit E, and I/R + biso+vit E. Cerebral I/R group underwent global ischemia by bilateral common carotid artery occlusion for 20 min. Treatment groups received drugs once daily intraperitoneally for 7 days before the I/R induction. Locomotive and cognitive behaviors were utilized by open-field and Morris water maze tests. After behavioral testing, the brain was removed and processed to evaluate cerebral infarct size, histopathologic changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) level. In I/R group tissue MDA and MPO levels and cerebral infarct size were significantly increased in comparison with the sham group. Furthermore, significant deficits were observed in locomotion and spatial memory after I/R. The areas of cerebral infarction, MPO, and MDA levels in biso, vit E, and combination group were significantly reduced compared with I/R group. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration in all treated groups with the most profound reduction in the combination group. According to the behavioral tests, administration of biso and/or vit E protected locomotive ability and improved spatial memory after cerebral I/R. Our findings show that biso and vit E have beneficial effects against the I/R injury and due to their synergistic effects when administered in combination, may have a more pronounced protective effect on the cerebral I/R injury.

Raíssa Soares Dos Anjos, Giovana Nóbrega de Pádua Walfrido, Rômulo Oliveira de Hollanda Valente, Luiz Alcino Gueiros, Alessandra Albuquerque Tavares Carvalho, Preeyan Patel, Stephen Porter, Jair Carneiro Leão, Igor Henrique Morais Silva

Support Care Cancer . 2020 Oct 27. doi: 10.1007/s00520-020-05847-6. Online ahead of print.

Abstract

Background: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws.

Methods: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws.

Results: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months.

Conclusion: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.

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.

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.

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.