Tocotrienols Activate Nrf2 Nuclear Translocation and Increase the Antioxidant- Related Hepatoprotective Mechanism in Mice Liver

Ahmed Atia, Nadia S Alrawaiq, Azman Abdullah

Curr Pharm Biotechnol . 2021;22(8):1085-1098. doi: 10.2174/1389201021666200928095950.

Abstract

Background: The most common preparation of tocotrienols is the Tocotrienol-Rich Fraction (TRF). This study aimed to investigate whether TRF induced liver Nrf2 nuclear translocation and influenced the expression of Nrf2-regulated genes.

Methods: In the Nrf2 induction study, mice were divided into control, 2000 mg/kg TRF and diethyl maleate treated groups. After acute treatment, mice were sacrificed at specific time points. Liver nuclear extracts were prepared and Nrf2 nuclear translocation was detected through Western blotting. To determine the effect of increasing doses of TRF on the extent of liver nuclear Nrf2 translocation and its implication on the expression levels of several Nrf2-regulated genes, mice were divided into 5 groups (control, 200, 500 and 1000 mg/kg TRF, and butylated hydroxyanisole-treated groups). After 14 days, mice were sacrificed and liver RNA was extracted for qPCR assay.

Results: 2000 mg/kg TRF administration initiated Nrf2 nuclear translocation within 30 min, reached a maximum level of around 1 h and dropped to half-maximal levels by 24 h. Incremental doses of TRF resulted in dose-dependent increases in liver Nrf2 nuclear levels, along with concomitant dosedependent increases in the expressions of Nrf2-regulated genes.

Conclusion: TRF activated the liver Nrf2 pathway resulting in increased expression of Nrf2-regulated cytoprotective genes.

Saminathan Shadisvaaran, Kok-Yong Chin, Mohd-Said Shahida, Soelaiman Ima-Nirwana, Xin-Fang Leong

J Oral Biosci . 2021 Jun;63(2):97-103. doi: 10.1016/j.job.2021.04.001. Epub 2021 Apr 20.

Abstract

Background: Periodontitis is a noncommunicable inflammatory disease of the soft tissue and bone surrounding the teeth in the jaw, which affects susceptible individuals with poor oral hygiene. A growing interest has been seen in the use of dietary supplements and natural products for the treatment and prevention of periodontitis. Vitamin E consists of two major groups, namely tocopherols and tocotrienols, which are botanical lipophilic compounds with excellent anti-inflammatory and antioxidant properties.

Highlight: This review aimed to summarize the preclinical and clinical findings on the effects of vitamin E on periodontitis. The current literature suggests that vitamin E could improve the periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing, thus highlighting the potential of vitamin E in the management of periodontitis.

Conclusion: Direct evidence for the use of vitamin E supplementation or treatment of periodontitis in humans is still limited. More well-designed and controlled studies are required to ascertain its effectiveness.

Daniel Conei, Mariana Rojas, Luis Santamaría, Jennie Risopatrón

Andrologia . 2021 Jun 21;e14140. doi: 10.1111/and.14140. Online ahead of print.

Abstract

Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. The purpose of this study was to determine the protective effect of vitamin E (VE) on the testicular development in embryos, foetuses and pubertal mice exposed to VPA, VPA+VE and only VE. Sixty pregnant adult female mice were used, to which they were administered 600 mg/kg of VPA (VPA groups), 600 mg/kg of VPA and 200 IU of VE (VPA+VE groups), 200 IU VE (VE groups) and 0.3 ml of 0.9% physiological solution (control groups), showing at 12.5 days post-coital (dpc), 17.5 dpc and 6 weeks postnatal testicular development, and proliferative and apoptotic indices. The groups treated with VPA presented a smaller testicular volume, with greater interstitial space and a delay in the conformation of the testicular cords, shorter lengths and diameters of the germinal epithelium, a smaller number of germline and somatic cells, an increase in cells apoptotic and less proliferation, with significant differences. VE-treated groups behaved similarly to controls. In conclusion, VE reduces the effects caused by VPA throughout testicular development, from embryonic stages, continuing until pubertal stages.

Ahmad H Alghadir, Sami A Gabr, Shahnawaz Anwer, Heng Li

Sci Rep . 2021 Jun 18;11(1):12867. doi: 10.1038/s41598-021-92076-4.

Abstract

This study examined the associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults. One hundred and six older adults (62 men, 44 women) within the age range of 56-81 years participated. The Global Physical Activity Questionnaire and the Loewenstein Occupational Therapy Cognitive Assessment were used to assess physical activity and cognitive function, respectively. Vitamin E (e.g., α-tocopherol and γ-tocopherol), oxidative stress markers (e.g., total antioxidant capacity and nitric oxide), and total homocysteine were estimated. There were significant associations between physical activity (high versus moderate versus poor) and all biomarkers (all p = 0.000, and p = 0.010 for γ-tocopherol). While total homocysteine and total antioxidant capacity were significantly associated with cognitive capacity (p = 0.000), vitamin E levels (e.g., α-tocopherol and γ-tocopherol) and nitric oxide (p = 0.354, 0.103 and 0.060, respectively) were not related to cognitive capacity in older adults. This study concludes that physical activity was associated with Vitamin E, oxidative stress markers, total homocysteine, and cognitive capacity in older adults. Although cognitive capacity was associated with total homocysteine and total antioxidant capacity, it was unrelated to vitamin E levels and nitric oxide in older adults.

Huikai Miao, Rongzhen Li, Dongni Chen, Jia Hu, Youfang Chen, Chunmei Xu, Zhesheng Wen

Ann Nutr Metab . 2021 Jun 18;1-11. doi: 10.1159/000515620. Online ahead of print.

Abstract

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common symptom, but prophylactic measures cannot still be carried out effectively. In addition, the efficacy of vitamin E in preventing peripheral neurotoxicity caused by chemotherapy is inconclusive. Therefore, we collected the relevant randomized controlled trials (RCTs) and performed a meta-analysis to examine whether the vitamin E has a positive effect in CIPN.

Methods: We searched PubMed, EMBASE, Cochrane, and other databases in December 2019 for eligible trials. Two reviewers conducted the analysis independently when studies were homogeneous enough.

Results: Eight RCTs, involving 488 patients, were identified. Upon pooling these RCTs, patients who received vitamin E supplementation of 600 mg/day had a lower incidence of CIPN (risk ratio [RR] 0.31; 95% confidence interval [CI] 0.14-0.65; p = 0.002) than the placebo group. Vitamin E played a key role in decreasing the incidence of peripheral neuropathy in the cisplatin chemotherapy group (RR 0.28; 95% CI 0.14-0.54; p = 0.0001). Moreover, vitamin E supplementation significantly decreased patients’ sural amplitude after 3 rounds of chemotherapy (RR -2.66; 95% CI -5.09 to -0.24; p = 0.03) in contrast with that of placebo supplementation, while no significant difference was observed when patients were treated with vitamin E after 6 rounds of chemotherapy. In addition, the vitamin E-supplemented group had better improvement in the neurotoxicity score and lower incidence of reflexes and distal paraesthesias than the control group.

Conclusion: Available data in this meta-analysis showed that vitamin E supplementation can confer modest improvement in the prevention of CIPN.

Rotimi Johnson Ojo, Gideon Agyiye Enoch, Faratu Saleh Adeh, Luret Carmen Fompun, Blessing Yohanna Bitrus, Meshack Anthony Kugama

J Parasit Dis . 2021 Jun;45(2):512-523. doi: 10.1007/s12639-020-01322-5. Epub 2021 Jan 3.

Abstract

Reinforcement of the body with exogenous antioxidants have been shown to mitigate the negative effects of African trypanosomiasis on the host and contribute greatly to their survival. This study was therefore conducted to evaluate the effects of oral administration of Vitamin E on the early stage of Trypanosoma brucei brucei infection. To achieve this, parasite free healthy rats were acclimatized for 2 weeks before they were divided into three groups. Two of the groups were infected by intraperitoneal inoculation of 1 × 10⁴ parasites/rat and monitored for the presence of Trypanosoma brucei brucei. Blood samples were collected from the infected rats from the second day post infection to detect the presence of parasites. Vitamin E treatment started day 4 post infection at the onset of parasitaemia. Parasites were monitored till the end of the study. The blood glucose level was determined using a glucometer; the lipid profile, liver and kidney biomarkers, electrolytes and protein were determined by colorimetric method using commercial kits. Haematological parameters were analysed using a sysmex haematology analyser. The results of this study showed that the infection adversely affected the biomarkers examined showing its negative effect on liver, kidney, haematological parameters and host electrolyte balance. Treatments with Vitamin E was however able to mitigate the negative effect of this infection. In conclusion, the treatment was able to ameliorate the anaemia and organ damage caused by Trypanosoma brucei brucei, extend the life span of the treated rats and greatly delay the time taken to get to the second stage of the infection.

Marina C Vera, Alvaro Lucci, Anabela C Ferretti, Adriano A Abbondanzieri, Carla G Comanzo, Florencia Lorenzetti, Gerardo B Pisani, María P Ceballos, Maria de L Alvarez, María C Carrillo, Ariel D Quiroga

J Nutr Biochem . 2021 Jun 17;108806. doi: 10.1016/j.jnutbio.2021.108806. Online ahead of print.

Abstract

Many cancer patients receive their classical therapies together with vitamin supplements. However, the effectiveness of these strategies is on debate. Here we aimed to evaluate how vitamin E supplementation affects the anticancer effects of interferon (IFN-α) using an early-model of liver cancer development (initiation-promotion, IP). Male Wistar rats subjected to this model were divided as follows: untreated (IP), IP treated with recombinant IFN-α-2b (6.5 × 10⁵ U/kg), IP treated with vitamin E (50 mg/kg), and IP treated with combination of vitamin E and IFN-α-2b. After treatments rats were fasted and euthanized and plasma and livers were collected. Combined administration of vitamin E and IFN-α-2b induced body weight drop, increased liver apoptosis and low levels of hepatic lipid levels. Interestingly, vitamin E and IFN-α-2b combination also induced an increase in altered hepatic foci number, but not in size. It seems that vitamin E acts on its antioxidant capability in order to block the oxidative stress induced by IFN-α-2b, blocking in turn its beneficial effects on preneoplastic livers, leading to harmful final effects. In conclusion, this study shows that vitamin E supplementation in IFN-α-2b-treated rats exerts unwanted effects; and highlights that in spite of being natural, nutritional supplements may not always exert beneficial outcomes when used as complementary therapy for the treatment of cancer.

Daniel Edem Kpewou, Faustina O Mensah, Collins A Appiah, Huseini Wiisibie Alidu, Vitus Sambo Badii

Heliyon . 2021 Jun 17;7(6):e07339. doi: 10.1016/j.heliyon.2021.e07339. eCollection 2021 Jun.

Abstract

Vitamin E is a potent antioxidant that helps to counteract oxidative stress in the body. Oxidative stress is known to greatly affect people living with HIV (PLWH) through the stimulation of HIV replication and apoptosis of CD4+ T cells. There is however, a paucity of scientific data on the serum levels of vitamin E among PLWH in Ghana, and hence, there is a need to assess its level because of the pivotal role it plays in cell longevity determination and the immune system enhancement of such persons. This study aims to assess the serum levels of vitamin E among PLWH undergoing highly active antiretroviral therapy at Ho Teaching Hospital, Ghana. In a cross-sectional study, serum vitamin E levels of 103 randomly selected PLWH aged 24-88 years who attended an antiretroviral therapy clinic at the Ho Teaching Hospital, Ghana, were measured by following standard protocols. A 24-hour dietary recall and food frequency questionnaire were employed to assess dietary intake. The results show that a high level of serum vitamin E deficiency (82.5%) was observed among the participants. Majority (91.3%) of the participants had normal serum zinc status. Participants’ serum vitamin E levels did not show significant correlation with their dietary intakes (correlation coefficient (ρ) = -0.094, p-value = 0.35). The prevalence of vitamin E deficiency among underweight, normal weight, overweight, and obese participants was 91.7%, 75.4%, 86.5%, and 91.7% respectively with no significant difference among these groups. There was no significant correlation between serum vitamin E levels and HIV infection duration (ρ = 0.010, p-value = 0.405) and HAART duration (ρ = 0.001, p-value = 0.313). The low serum vitamin E levels found in this study suggests that the participants could potentially be at an increased risk of developing oxidative stress and its effects.

Hongxing Dang, Jing Li, Chengjun Liu, Feng Xu

Front Nutr . 2021 Jun 16;8:648442. doi: 10.3389/fnut.2021.648442. eCollection 2021.

Abstract

Background: Literature is scarce on the assessment of vitamin E status in septic children. We aim to investigate the prevalence of vitamin E deficiency in critically ill children with sepsis and septic shock and its association with clinical features and outcomes. Methods: We compared serum vitamin E status between the confirmed or suspected infection and no infection groups, the sepsis shock and no sepsis shock groups upon pediatric intensive care unit admission. Clinical characteristics were compared in subgroup patients with and without vitamin E deficiency. The association between vitamin E deficiency and septic shock were evaluated using univariate and multivariable methods. Results: 182 critically ill children with confirmed or suspected infection and 114 without infection were enrolled. The incidence of vitamin E deficiency was 30.2% in the infection group and 61.9% in the septic shock subgroup (P < 0.001). Thirty-days mortality in critically ill children with vitamin E deficiency was significantly higher than that without vitamin E deficiency (27.3 vs. 14.2%, P < 0.05). Vitamin E levels were inversely associated with higher pediatric risk of mortality (r = – 0.238, P = 0.001) and cardiovascular sequential organ failure assessment (r = -0.249, p < 0.001) scores in critically ill children with infection. In multivariable logistic regression, vitamin E deficiency showed an independent effect on septic shock (adjusted OR: 6.749, 95%CI: 2.449-18.60, P < 0.001). Conclusion: Vitamin E deficiency is highly prevalent in critically ill children with sepsis and contributed to the septic shock.

Nodam Park, Soo A Kim, Kiyoung Oh, Yuntae Kim, Siha Park, Joon Yeop Kim, Namhun Heo

Ann Rehabil Med . 2021 Jun 14. doi: 10.5535/arm.21038. Online ahead of print.

Abstract

Objective: To investigate the association between vitamin E and handgrip strength (HGS) with multiple factors.

Methods: A total of 1,814 participants were included (822 men and 981 women) from the Korean subjects of the 7th Korea National Health and Nutrition Examination Survey in 2018. Data were analyzed using multiple logistic regression to determine the correlation between vitamin E and HGS with potential confounding factors.

Results: In the multiple logistic regression model, only the young age group (19-40 years) of men showed a positive relationship between vitamin E and HGS. However, in older age groups (41-80 years) of men and all age groups of women, there was no statistically significant result. After adjusting for confounding factors, young men showed higher vitamin E levels and higher HGS. Conversely, women and older age groups did not show significant results after adjusting for confounding factors.

Conclusion: In this study, the serum vitamin E level had a positive effect on HGS in young men (<40 years). Further research is needed on this topic regarding vitamin E intake and other objective measures.