Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons

Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA

Int J Mol Sci. 2019 Dec 28;21(1). pii: E220. doi: 10.3390/ijms21010220.

Abstract

B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival.

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Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial

Tan GCJ, Tan SMQ, Phang SCW, Ng YT, Ng EY, Ahmad B, Palamisamy UDM, Kadir KA

Ther Adv Endocrinol Metab. 2019 Dec 25;10:2042018819895462. doi: 10.1177/2042018819895462. eCollection 2019.

Abstract

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.

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Clinical Efficacy of Topical CoQ10 and Vitamin-E Eye-drop in Retinopathy of Prematurity

Akdogan M, Polat O

Med Hypothesis Discov Innov Ophthalmol. 2019 Winter;8(4):291-297.

Abstract

Treatment strategy for retinopathy of prematurity (ROP) includes anti-vascular endothelial growth factor (anti-VEGF) and/or laser therapy. The aim of this study was to investigate the clinical effects of topical Coqun® eye drop (CoQ10 and Vitamin-E) on the progression and treatment of ROP. One hundred and ten infants with type 1 ROP who received Coqun® (Coqun group) and 131 infants with type 1 ROP who did not receive Coqun® (control group) were included in this retrospective analysis. All patients were follow-up until retinal vascular maturation was complete. Intravitreal bevacizumab (IVB) injection or laser photocoagulation (LPC) were apply if needed. Treatment frequency, treatment response and mean follow-up time were compare. The number of IVB was similar between the groups, but infants in the Coqun group underwent significantly fewer LPC procedure than those in the control group (P = 0.022). The mean follow-up time was significantly shorter in infants receiving Coqun® in stage 1 ROP (P = 0.017) and similar in stages 2-4 ROP and aggressive posterior retinopathy of prematurity (APROP). The number of LPC procedure was fewer in the Coqun group in APROP (P = 0.043). These results indicate that faster retinal vascular maturation in infants with low-grade ROP and lower number of treatments with APROP could be achieve with Coqun® therapy.

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Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells

Ramdas P, Radhakrishnan AK, Abdu Sani AA, Kumari M, Anandha Rao JS, Abdul-Rahman PS

Biomolecules. 2019 Dec 21;10(1). pii: E19. doi: 10.3390/biom10010019.

Abstract

Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.

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Tocotrienols: The New Vitamin E in Palm soup fights prostate cancer

The study of Vitamin E and prostate cancer is hotly contested. This topic review Vitamin E and prostate cancer. The most important question is whether taking vitamin E increase men risk of prostate cancer? That study was published in the Journal of the American Medical Association (JAMA) about the extended findings of the SELECT trial which stated that vitamin E can increase the risk of prostate cancer , got more people taking about prostate cancer and Vitamin E supplement. However, there are significant things one should know about the study and about vitamin E before taking vitamin E supplements .

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Chemoprotective and antiobesity effects of tocols from seed oil of Maqui-berry: Their antioxidative and digestive enzyme inhibition potential

Bastías-Montes JM, Monterrosa K, Muñoz-Fariña O, García O, Acuña-Nelson SM, Vidal-San Martín, Quevedo-Leon R, Kubo I, Avila-Acevedo JG, Domiguez-Lopez M, Wei ZJ, Thakur K, Cespedes-Acuña CL

Food Chem Toxicol. 2019 Dec 17:111036. doi: 10.1016/j.fct.2019.111036.

Abstract

Maqui-berry (Aristotelia chilensis) is the emerging Chilean superfruit with high nutraceutical value. Until now, the research on this commodity was focused on the formulations enriched with polyphenols from the pulp. Herein, contents of tocols were compared in the seed oil of Maqui-berry obtained through three different extraction methods followed by determining their antioxidative and enzyme inhibitions in-vitro. Firstly, oilseed was extracted with n-hexane (Soxhlet method), chloroform/methanol/water (Bligh and Dyer method) and pressing (industrial). These samples were used to access their effects against DPPH, HORAC, ORAC, FRAP, Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase. All the isomers of tocopherol and tocotrienol were identified, and β-sitosterol was the only sterol found in higher amounts than other vegetable oils. The Bligh and Dyer method could lead to the highest antioxidative capacity compared to Soxhlet and press methods likely because the latter have a higher amount of tocopherols. Further, seed oil from Maqui berry and their tocols (α, β, γ, δ-tocopherols, tocotrienols, and β-sitosterol) warrant clinical investigation for their antioxidative and antiobesity potential. Taken together, these findings provide relevant and suitable conditions for the industrial processing of Maqui-berry.

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Debunking myths on palm oil

Countless readers of The Hindu BusinessLine are once again being misled to believe that palm oil is detrimental to heart health. The publication ran an article by Balram Bhargava and Prabhkaran Dorairaj claiming, “Both past research and new evidence point to the ill effects on populations.” This statement is not just grossly inaccurate. It does an extreme disservice to the Indian population now experiencing an apparent uptick in cardiovascular disease.

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Nutritional Neuropathies

Gwathmey KG, Grogan J

Muscle Nerve. 2019 Dec 14. doi: 10.1002/mus.26783.

Abstract

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Though these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

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Evaluation of oxidative stress in caprine anaplasmosis and effect of vitamin E-selenium in monitoring oxidative stress

Dhanasree G, Pillai UN, Deepa C, Ambily VR, Shynu M, Sunanda C

Trop Anim Health Prod. 2019 Dec 14. doi: 10.1007/s11250-019-02175-8.

Abstract

Caprine anaplasmosis is an economically important tick-borne rickettsial disease that affects goats all over the world. Microscopic examination of stained blood smears from 162 animals revealed inclusion bodies of Anaplasma spp. in 24 cases. Genus specific PCR for Anaplasma spp. yielded positive results in 22 cases. All the diseased animals showed a significant fall in the mean values of antioxidants such as reduced glutathione, superoxide dismutase and catalase and a significant increase in the level of lipid peroxidation. Out of the 22 animals positive for anaplasmosis both in blood smear and PCR, 16 female non pregnant goats selected for study were divided into two groups consisting of eight animals each. Animals belonging to groups I and II were treated with oxytetracycline dihydrate. In addition, animals of group II were supplemented with vitamin E-selenium combination. Oxidative stress parameters were rechecked on the 10th day of treatment. At the end of the study period, a significant reduction in malondialdehyde level and a significant increase in mean value of superoxide dismutase were detected in group II. While there was a significant reduction in lipid peroxidation and a significant increase in superoxide dismutase and catalase values within both the groups after treatment, reduced glutathione showed no significant difference within the group.

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