Blog Archives

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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Vitamin E sequestration by liver fat in humans

Violet PC, Ebenuwa IC, Wang Y, Niyyati M, Padayatty SJ, Head B, Wilkins K, Chung S, Thakur V, Ulatowski L, Atkinson J, Ghelfi M, Smith S, Tu H, Bobe G, Liu CY, Herion DW, Shamburek RD, Manor D, Traber MG, Levine M.

JCI Insight. 2019 Dec 10. pii: 133309. doi: 10.1172/jci.insight.133309.

Abstract

BACKGROUND We hypothesized that obesity-associated hepato-steatosis served as a pathophysiologic chemical depot for fat-soluble vitamins and altered normal physiology. Using α-tocopherol (vitamin E) as a model vitamin, pharmacokinetics and kinetics principles were utilized to determine whether excess liver fat sequestered α-tocopherol in women with obesity-associated hepato-steatosis vs healthy controls.METHODS Custom-synthesized deuterated α-tocopherols (d3- and d6-α-tocopherols) were administered to hospitalized healthy women and women with hepato-steatosis under IND guidelines. Serial samples obtained over 72 hours were analyzed by LC/MS. Fluorescent-labelled α-tocopherol was custom-synthesized for cell studies.RESULTS In healthy subjects, 85% of intravenous d6-α-tocopherol disappeared from the circulation within 20 minutes but reappeared within minutes and peaked at 6-8 hours. d3- and d6-α-Tocopherols localized to lipoproteins. Lipoprotein redistribution occurred only in vivo within 1h, indicating a key role of liver in rapid uptake and re-release into the circulation. Compared to healthy subjects, subjects with hepato-steatosis had similar d6-α-tocopherol entry rates into liver, but reduced initial release rates (p<0.001). Similarly, pharmacokinetics parameters of AUC and Maximum Concentration (Cmax) were reduced (AUC0-8 ,p<0.01;Cmax p<0.02) in hepato-steatosis subjects, indicating reduced hepatic d6-α-tocopherol output. Reduced kinetics and pharmacokinetics parameters (AUC and Cmax) in hepato-steatosis subjects who received 2 mg were mirrored by similar reductions in healthy subjects when comparing 5 and 2 mg doses. In vitro, fluorescent-labelled α-tocopherol localized specifically to lipid in fat-loaded hepatocytes, indicating sequestration.CONCLUSIONS The unique role of the liver in vitamin E physiology is dysregulated by excess liver fat. Obesity-associated hepato-steatosis may produce unrecognized hepatic vitamin E sequestration, which might subsequently drive liver disease. Our findings raise the possibility that hepato-steatosis may similarly alter hepatic physiology of other fat-soluble vitamins.

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Alpha-Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Cabral EV, Vieira LD, Sant'Helena BRM, Ribeiro VS, Farias JS, Aires RS, Paz ST, Muzi-Filho H, Paixão AD, Vieyra A

Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1151-1165. doi: 10.1111/1440-1681.13161.

Abstract

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of CrCl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.

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Effects of pentoxifylline and tocopherol on a rat-irradiated jaw model using micro-CT cortical bone analysis

Nguyen TTH, Eo MY, Seo MH, Myoung H, Kim SM, Lee JH

Eur Arch Otorhinolaryngol. 2019 Dec;276(12):3443-3452. doi: 10.1007/s00405-019-05600-8.

Abstract

PURPOSE:

A combination of pentoxifylline (PTX) and tocopherol (TP) is believed to reduce chronic fibrosis and induce bone healing in osteoradionecrosis (ORN) of the mandible, but evidence of its therapeutic effectiveness for cortical bone is lacking. This study was designed to determine the effect of combined PTX and TP (PTX + TP) on mandibular cortical bone remodeling in a rat model of ORN, using micro-CT and histological analysis.

METHODS:

Forty-eight 8-week-old male Sprague-Dawley rats were randomly divided into irradiated (n = 40) and non-irradiated (n = 8) groups. Animals in the irradiated group were divided into four sub-groups, including PTX, TP, PTX + TP, and normal saline. Three weeks after irradiation, mandibular posterior tooth extraction was performed, and animals were sacrificed 7 weeks after irradiation. The mandibles were analyzed using micro-CT and histological evaluation.

RESULTS:

The alveolar bone height, cortical bone thickness, cortical bone volume, and total cortical bone surface of the PTX + TP group were significantly greater than those of other irradiated groups (p < 0.05). In 3D reconstructed images, the residual volumes of cortical and cancellous bone were inadequate in the irradiated groups.

CONCLUSION:

We found that a combination of PTX and TP improved quality and quantity of cortical bone in irradiated rat mandibles, thus providing supporting evidence of its utility as a treatment and prophylactic agent in ORN. We observed inadequate volumes of cortical and cancellous bone in ORN mandibles, suggesting that cortical bone could play an important role in further ORN studies.

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