Effects of Gamma-Tocotrienol on Intestinal Injury in a GI-Specific Acute Radiation Syndrome Model in Nonhuman Primate

Sarita Garg, Tarun K Garg, Stephen Y Wise, Oluseyi O Fatanmi, Isabelle R Miousse, Alena V Savenka, Alexei G Basnakian, Vijay K Singh, Martin Hauer-Jensen

Int J Mol Sci . 2022 Apr 22;23(9):4643. doi: 10.3390/ijms23094643.


The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury.

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Dietary Vitamin E intake is associated with a reduced risk of developing digestive diseases and NAFLD

Eleonora Scorletti, Kate Townsend Creasy, Marijana Vujkovic, Mara Vell, Inuk Zandvakili, Daniel J Rader, Kai Markus Schneider, Carolin V Schneider

Am J Gastroenterol . 2022 Mar 14. doi: 10.14309/ajg.0000000000001726. Online ahead of print.


Introduction: Vitamin E supplementation is recommended for the treatment of non-alcoholic fatty liver disease (NAFLD) for nondiabetic patients, but its preventative effects are unclear.

Methods: We assessed dietary Vitamin E intake with disease phenotypes and evaluated Vitamin E levels with the development of NAFLD.

Results: Data from >210,000 participants demonstrate that increased dietary Vitamin E associates with reduced rates of several gastrointestinal diseases and reduced overall mortality. Diabetic and overweight subjects with increased Vitamin E intake have fewer NAFLD diagnoses.

Conclusion: Our findings reveal the relevance of Vitamin E consumption for several gastrointestinal diseases and warrant further mechanistic and therapeutic investigations.

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Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

Ali Qusay Khalid, Saatheeyavaane Bhuvanendran, Kasthuri Bai Magalingam, Premdass Ramdas, Mangala Kumari, Ammu Kutty Radhakrishnan

Nutrients . 2021 Nov 12;13(11):4056. doi: 10.3390/nu13114056.


The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.

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Evaluation of common genetic variants in vitamin E-related pathway genes and colorectal cancer susceptibility

Qiuyi Zhang, Yixuan Meng, Mulong Du, Shuwei Li, Junyi Xin, Shuai Ben, Zhengdong Zhang, Dongying Gu, Meilin Wang

Arch Toxicol . 2021 May 19. doi: 10.1007/s00204-021-03078-0. Online ahead of print.


Vitamin E is effective for preventing the risk of cancer. However, few studies have elucidated the mechanism of vitamin E in cancer occurrence. Herein, we aimed to identify the genetic variants in vitamin E-related pathway genes associated with colorectal cancer risk. We applied logistic regression models to assess the association between single-nucleotide polymorphisms (SNPs) in vitamin E-related pathway genes and colorectal cancer risk in the Chinese and European population. The false discovery rate (FDR) method was used to correct multiple comparisons. The mRNA and protein expression analysis were evaluated in public database and in-house RNA-Seq data. SCARB1 rs73227586 was identified significantly increased risk of colorectal cancer in the Chinese population (odd ratio (OR) = 1.46, 95% confidence interval (CI) = 1.22-1.75, P = 2.99 × 10-5). This finding was further validated in the European population (OR = 1.11, 95% CI = 1.02-1.20, P = 1.44 × 10-2). Additionally, the mRNA and protein expression of SCARB1 were markedly up-regulated in colorectal tumor tissues. Moreover, rs73227586 T allele could increase the minimum free energy (MFE) and weaken binding ability to transcription factor ELL2. Our findings indicated that SCARB1 may play a carcinogenic role in colorectal cancer. Genetic variants in vitamin E-related pathway genes may concern to be predictors of colorectal cancer risk.

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