Effects of Calcium and Annatto Tocotrienol Supplementation on Bone Loss Induced by Pantoprazole in Male Rats

Kok-Yong Chin, Benjamin Ka Seng Thong, Rhivaldy Faahim Kamalulloh, Nur Vaizura Mohamad, Sok Kuan Wong, Azlan Mohd Arlamsyah, Rahma Triliana, Ima Nirwana Soelaiman

Drug Des Devel Ther . 2020 Jul 2;14:2561-2572. doi: 10.2147/DDDT.S260565. eCollection 2020.

Abstract

Purpose: Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol or vitamin D3 (Caltrate Plus) in preventing bone loss caused by pantoprazole.

Methods: Three-month-old Sprague Dawley male rats (n=30) were randomised into five groups (n=6/group). Bone loss was induced by pantoprazole (3 mg/kg p.o.) in four groups, and they were treated concurrently with either calcium carbonate (77 mg p.o.), calcium carbonate (77 mg p.o.) plus annatto tocotrienol (60 mg/kg p.o.) or Caltrate Plus (31 mg p.o.) for 60 days. The rats were euthanised at the end of the experiment, and their femurs were harvested for X-ray micro-computed tomography, bone cellular histomorphometry and bone mechanical strength analysis.

Results: Pantoprazole caused significant deterioration of trabecular bone microstructures but did not affect other skeletal indices. Calcium supplementation with or without annatto tocotrienol prevented the deterioration of trabecular microstructures at the femur but did not improve other skeletal indices. Annatto tocotrienol did not enhance the skeletal actions of calcium, whereas Caltrate Plus did not affect the bone health indices in these rats.

Conclusion: Calcium supplementation per se can prevent the deterioration of bone trabecular microstructures in rats receiving long-term treatment of pantoprazole.

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Tocol Prophylaxis for Total-body Irradiation: A Proteomic Analysis in Murine Model

Elliot Rosen, Oluseyi O Fatanmi, Stephen Y Wise, V Ashutosh Rao, Vijay K Singh

Health Phys . 2020 Jul;119(1):12-20. doi: 10.1097/HP.0000000000001221.

Abstract

The aim of this study was to analyze the changes in mouse jejunum protein expression in response to prophylactic administration of two promising tocols, γ-tocotrienol (GT3) and α-tocopherol succinate (TS), as radiation countermeasures before irradiation to elucidate the molecular mechanism(s) of their radioprotective efficacy. Mice were administered GT3 or TS (200 mg kg) subcutaneously 24 h prior to exposure to 11 Gy Co γ-radiation, a supralethal dose for mice. Jejunum was harvested 24 h post-irradiation. Results of the two-dimensional differential in-gel electrophoresis (2D-DIGE), coupled with mass spectrometry, and advanced bioinformatics tools suggest that the tocols have a corresponding impact on expression of 13 proteins as identified by mass spectrometry. Ingenuity Pathway Analysis (IPA) reveals a network of associated proteins involved in inflammatory response, organismal injury and abnormalities, and cellular development. Relevant signaling pathways including actin cytoskeleton signaling, RhoA signaling, and Rho family GTPase were identified. This study reveals the major proteins, pathways, and networks involved in preventing the radiation-induced injury in gut that may be contributing to enhanced survival.

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Effect of Vitamins D and E on the Proliferation, Viability, and Differentiation of Human Dental Pulp Stem Cells: An In Vitro Study

Lina M Escobar, Zita Bendahan, Andrea Bayona, Jaime E Castellanos, María-Clara González

Int J Dent . 2020 Jul 1;2020:8860840. doi: 10.1155/2020/8860840. eCollection 2020.

Abstract

Introduction: The aim of the present study was to determine the effects of vitamins D and E on the proliferation, morphology, and differentiation of human dental pulp stem cells (hDPSCs).

Methods: In this in vitro experimental study, hDPSCs were isolated, characterized, and treated with vitamins D and E, individually and in combination, utilizing different doses and treatment periods. Changes in morphology and cell proliferation were evaluated using light microscopy and the resazurin assay, respectively. Osteoblast differentiation was evaluated with alizarin red S staining and expression of RUNX2, Osterix, and Osteocalcin genes using real-time RT-PCR.

Results: Compared with untreated cells, the number of cells significantly reduced following treatment with vitamin D (49%), vitamin E (35%), and vitamins D + E (61%) after 144 h. Compared with cell cultures treated with individual vitamins, cells treated with vitamins D + E demonstrated decreased cell confluence, with more extensive and flatter cytoplasm that initiated the formation of a significantly large number of calcified nodules after 7 days of treatment. After 14 days, treatment with vitamins D, E, and D + E increased the transcription of RUNX2, Osterix, and Osteocalcin genes.

Conclusions: Vitamins D and E induced osteoblastic differentiation of hDPSCs, as evidenced by the decrease in cell proliferation, morphological changes, and the formation of calcified nodules, increasing the expression of differentiation genes. Concurrent treatment with vitamins D + E induces a synergistic effect in differentiation toward an osteoblastic lineage.

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Cardiac and Renal Protective Effect of Vitamin E in Dexamethasone-Induced Oxidative Stressed Wistar Rats

Daniel U Owu, Idara A Okon, Usenobong F Ufot, Justin A Beshel

Niger J Physiol Sci . 2020 Jun 30;35(1):52-60.

Abstract

Vitamin E has been used as antioxidant and in the treatment of various ailments due to oxidative stress. The cardio-protective effect of vitamin E in dexamethasone induced oxidative stress was studied. Forty Wistar rats were randomly assigned to four groups of 10 rats each. Control group received normal rat chow. Oxidative stress was induced using 30µg/kg body weight of dexamethasone (DEX) intraperitonealy in DEX+Vit E and DEX only groups while Vitamin E was administered orally at a dose of 300 IU/kg to Vitamin E only group and DEX+Vit E group daily for 14 days. All animals were fed ad libitum and had free access to water. Blood samples were obtained by cardiac puncture for biochemical analyses while heart and kidney were processed for histological staining. The result shows a significant (p<0.05) decrease in serum nitric oxide, bilirubin and superoxide dismutase concentration in DEX-only group which was elevated following vitamin E treatment. The angiotensin converting enzyme and lactate dehydrogenase enzyme activities were significantly (p<0.01) elevated in DEX-only group compared with control and DEX+Vit E groups. These enzyme levels were significantly (p<0.01) reduced in DEX + vitamin E group. The histology of the heart and the kidney in DEX-only group showed cardiac hypertrophy and kidney injury but were ameliorated by vitamin E treatment. The results suggest that vitamin E has cardiac and renal protective effect and ameliorates oxidative injury to the heart and kidney due to oxidative stress.

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Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

Lavinia Casati, Francesca Pagani, Roberto Maggi, Francesco Ferrucci, Valeria Sibilia

Int J Mol Sci . 2020 Jun 30;21(13):4661. doi: 10.3390/ijms21134661.

Abstract

Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 μg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/β-catenin signalling pathway activation. In fact, δ-TT increased β-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/β-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of β-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound.

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Studies on the growth inhibiting and non-cytotoxic effects of tocotrienols on selected cancer cell lines

Aleksandra Szulczewska-Remi, Małgorzata Nogala-Kalucka

Acta Sci Pol Technol Aliment . Apr-Jun 2020;19(2):139-147. doi: 10.17306/J.AFS.0787.

Abstract

Background: Tocotrienols found in certain plant oils, like palm, rice bran, grapeseed and annatto seeds, have been reported to possess beneficial properties for humans, including cancer prevention. Since studies on their beneficial effects on human breast cancer cells have been extensively reviewed, the current understanding of how tocotrienols affect other cancer cells deserves further research. Therefore, the aim of this study was to investigate the antiproliferative and non-cytotoxic effects of tocotrienols on human hepatoma HepG2 and colon colorectal Caco-2 cell cultures.

Methods: The cells were exposed to alpha-, beta-, gamma- or delta-tocotrienols at various concentrations and the antiproliferative activities were measured using MTS-based CellTiter 96 followed by a methylene blue assay for counting cells to evaluate the potential toxicity.

Results: The research on HepG2 showed statistically similar cytotoxic effects for both beta- and delta-T3 with no effects for alpha- and gamma-T3. Promising results were found for alpha-, beta- and gamma-T3 against CaCo-2.

Conclusions: The exact reasons for the sensitivity of liver cancer cells to tocotrienols are unknown. Inhibition is time and dose-dependent, therefore tocotrienols’ homologs show very high toxic or no effects. Tocotrienols appeared to be effective against colon cancer cells. Still, future investigation is necessary to explain the different mechanism of actions to support the antiproliferative effects of these homologs against colon cancer cells.

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Vitamin E Deficiency: An Under-Recognized Cause of Dystonia and Ataxia Syndrome

Harsh V Gupta, Steven Swank, Vibhash D Sharma

Ann Indian Acad Neurol . May-Jun 2020;23(3):372-374. doi: 10.4103/aian.AIAN_29_20.

A 43-year-old right-handed man was seen in the clinic for an evaluation of progressive gait difficulty. He initially developed tingling in his hands and feet at the age of 30 years. After 3 years of initial symptoms, he developed weakness in his lower distal extremities. His symptoms progressed over the years and he developed unsteady gait, double vision, speech changes, and tremor in his right hand and head. He also complained of diarrhea (five to six loose watery bowel movements a day) and required frequent emergency evaluations for the management of the same. He was found to have colonic dilatation (11.4 cm). His past medical history was significant for jejunal resection at the time of birth. There was no family history of similar neurological problems.

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Melatonin and vitamin E alleviate homocysteine-induced oxidative injury and apoptosis in endothelial cells

Gurkan Aykutoglu, Musa Tartik, Ekrem Darendelioglu, Adnan Ayna, Giyasettin Baydas

Mol Biol Rep . 2020 Jun 26. doi: 10.1007/s11033-020-05607-z. Online ahead of print.

Abstract

A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.

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Vitamin E Savior?

A new study gives hope that vitamin E may defend against catastrophic disease. The research, recently published in the Journal of Cerebral Blood Flow & Metabolism, discovered that 10 weeks of preventive use of the tocotrienol (TCT) form of vitamin E on dogs offered robust protection in the event of a stroke.

Vitamin E occurs naturally in eight forms, including tocopherols and TCTs. “Most of the previous studies on vitamin E was on tocopherols,” says lead author Chandan Sen, PhD. “Tocotrienols are hardly studied, but we found that it’s much more neural protective than the others.

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