Protective Effect of Vitamin E on Cadmium-Induced Renal Oxidative Damage and Apoptosis in Rats

Jing Fang, Shenglan Xie, Zhuo Chen, Fengyuan Wang, Kejie Chen, Zhicai Zuo, Hengmin Cui, Hongrui Guo, Ping Ouyang, Zhengli Chen, Chao Huang, Wentao Liu, Yi Geng

Biol Trace Elem Res . 2021 Dec;199(12):4675-4687. doi: 10.1007/s12011-021-02606-4. Epub 2021 Feb 9.


Cadmium (Cd), a widely distributed heavy metal, is extremely toxic to the kidney. Vitamin E (VE) is an important antioxidant in the body. It is known that VE exerts a protective effect on renal oxidative damage caused by Cd, but the effect and mechanism of VE on apoptosis are not fully understood. Thus, we conducted this study to explore the protective effect of VE on Cd-induced renal apoptosis and to elucidate its potential mechanism. Thirty-two 9-week-old male Sprague-Dawley rats were randomly divided into four groups, namely control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2), and VE + Cd (100 mg/kg VE + 5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for 4 weeks. The results showed that Cd exposure significantly reduced the weight of the body and kidney, elevated the accumulation of Cd in the kidney as well as the levels of BUN and Scr in serum, caused renal histological alterations, decreased the GSH and T-AOC contents and antioxidant enzyme (SOD, CAT, GSH-PX) activities, and increased renal MDA content. And the increased number of TUNEL-positive cells by Cd was accompanied by upregulated mRNA and protein expressions of apoptotic regulatory molecules (Bax, Caspase-3, GRP94, GRP78, Caspase-8) and downregulated Bcl-2 expressions. However, the combined treatment of Cd and VE could restore the above parameters to be close to those in the control rats. In conclusion, VE supplement could alleviate Cd-induced rat renal damage and oxidative stress through enhancing the antioxidant defense system and inhibiting apoptosis of renal cells.

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Scrubbed Palm Fatty Acid Distillate as Vitamin E Concentrate

Amnart Soontornchatchawate, Supachai Chintanalert, Prakob Kitchaiya, Apinan Namkanisorn

J Oleo Sci . 2021 Dec 8. doi: 10.5650/jos.ess21169. Online ahead of print.


Vitamin E (VitE) production from crude palm oil (CPO) has been extensively studied and industrially conducted. VitE in CPO is in the range of 600 to 1,000 ppm, and is usually produced from one of the main by-products of edible palm oil production, namely palm fatty acid distillate (PFAD). PFAD contains 4,000 to 5,500 ppm of VitE, and is produced from deodorization process of palm oil purification. This paper presents an innovative process of VitE concentrate production from CPO. A scrubber was designed and installed between the deodorizer and conventional PFAD scrubber. The main objective of this new scrubber was a recovery of glycerides from PFAD. This new scrubber is operated at 150 to 160℃. The scrubbed oil is named as Scrubbed Palm Fatty Acid Distillate (S-PFAD). This simple and efficient modified process can retrieve glycerides as S-PFAD at 0.3% recovery and it enhances VitE concentration in S-PFAD to the range of 28,000 to 32,000 ppm, which is the highest concentration of VitE that has ever been produced in the palm oil production. Fatty acids and glycerides in S-PFAD were esterified and transesterified to methyl esters. The methyl esters were evaporated from S-PFAD, and S-PFAD residue oil contained 24.7% VitE.

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Associations of Dietary and Circulating Vitamin E Level With Metabolic Syndrome. A Meta-Analysis of Observational Studies

Yi Zhang, Jun Ding, Hongbin Guo, Ze Liu, Qi Liu, Yusheng Li, Dianzhong Zhang, Jieyu Liang

Front Nutr . 2021 Dec 8;8:783990. doi: 10.3389/fnut.2021.783990. eCollection 2021.


Objective: The associations of dietary and circulating vitamin E level with metabolic syndrome (MetS) remains conflicting. This meta-analysis of observational study was therefore employed to investigate the issue above. Methods: The PubMed, Web of Science and Embase database were searched up to April 2021. The observational studies on the associations of dietary and circulating vitamin E level with MetS were specified. The pooled relative risk (RR) of MetS for the highest vs. lowest dietary and circulating vitamin E level, and the standard mean difference (SMD) of dietary and circulating vitamin E level for MetS vs. control subjects, were calculated. Results: A total of 25 observational studies with 51,276 participants, were included in this meta-analysis. The overall multi-variable adjusted RR demonstrated that the dietary vitamin E level was inversely associated with MetS (RR = 0.92, 95%CI: 0.85-1.00; P = 0.044). In addition, the dietary vitamin E level in MetS was also lower than that in control subjects according to the overall combined SMD (SMD = -0.08, 95%CI: -0.14 to -0.02; P = 0.024). On the other hand, the overall multi-variable adjusted RR showed no significant relationship between the circulating vitamin E level and MetS (RR = 1.46, 95%CI: 0.85-2.48; P = 0.17). However, the circulating vitamin E level in MetS was lower than that in control subjects according to the overall combined SMD (SMD = -0.58, 95%CI: -1.04 to -0.13; P = 0.013). Conclusions: The results of this meta-analysis suggest that the dietary vitamin E level is inversely associated with MetS. On the other hand, current evidence is still insufficient to conclude a relationship between the circulating vitamin E level and MetS. More well-designed prospective cohort studies are needed to address the issues further.

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Vitamin E-Enhanced Liners in Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis

Qian-Yue Cheng, Bin-Fei Zhang, Peng-Fei Wen, Jun Wang, Lin-Jie Hao, Tao Wang, Hui-Guang Cheng, Ya-Kang Wang, Jian-Bin Guo, Yu-Min Zhang

Biomed Res Int . 2021 Dec 6;2021:3236679. doi: 10.1155/2021/3236679. eCollection 2021.


Objective: Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty.

Methods: We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1.

Results: From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; P < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; P = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores.

Conclusion: Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.

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Enhancing oxidative stability of tocopherol-enriched edible oils using short-term exposure to microwave irradiation

Hyuk Choi, HeeSun Na, SungHwa Kim, YoonHee Lee, JaeHwan Lee

J Food Sci . 2021 Dec;86(12):5272-5281. doi: 10.1111/1750-3841.15964. Epub 2021 Nov 18.


The effect of microwave irradiation on the oxidative stability of tocopherol-enriched corn oil at temperatures of 60 or 100°C was evaluated using the Rancimat assay. Short durations of microwave treatment (1 min) on 10-g oil aliquots were found to increase the induction period of corn oil samples containing 500 and 1000 ppm tocopherol by 7.7% and 9.9%, respectively compared to control oils. The moisture content of tocopherol-enriched corn oil decreased by 15% compared to that of corn oil after 1 min of microwave treatment. At 100°C, 1000 ppm tocopherol-enriched corn oil received 3 min of microwave treatment had 5.8% and 9.9% lower primary and secondary oxidation products than control groups, respectively while this effect was not clearly observed for oils stored at 60°C. However, 15 min of microwave irradiation accelerated the rates of lipid oxidation in corn oils irrespective of the addition of tocopherol. Content of α- and γ-tocopherols in 1 min of microwave irradiated samples remained more by 28.8 and 5.8%, respectively than those of controls after 9 h heat treatment at 100°C. Overall, microwave irradiation within 3 min can increase the oxidative stability of 10 g-corn oils, especially at 100°C, which could be due to the reduced moisture content in the bulk oil matrix. Practical Application: A microwave oven is an irreplaceable home appliance and is widely used in households. Short time exposure to microwave irradiation can remove moisture efficiently from edible oils without the formation of oxidation products, which could increase the oxidative stability of these oils, especially under frying conditions. The results of this study can be utilized to ensure a longer shelf-life of fried products in the food industry by short time treatment of microwave irradiation.

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Vitamin E supplementation reduces stress levels from orthodontic force in Wistar rats ( Rattus norvegicus)

Erliera Sufarnap, Syafruddin Ilyas, Ervina Sofyanti, Darmayanti Siregar, Yumi Lindawati, Trio Novalia, Henny Kurnianingsih

Saudi Dent J . 2021 Dec;33(8):912-916. doi: 10.1016/j.sdentj.2021.09.004. Epub 2021 Sep 13.


Background: Orthodontic tooth movement is mediated by the inflammation process. Inflammation induces pain and increases the level of cortisol hormone as it triggers stress. The aim of this research was to observe the effects of vitamin E (VE) supplementation in reducing stress levels from orthodontic force in Wistar rats (Rattus norvegicus).

Methods: Wistar rats (n = 56) were divided into two groups: group 1 as the control group, and group 2 as the experimental group (VE group). VE supplemented for 14 days prior application of the separator as an orthodontic force. Each group was divided into four subgroups (n = 7), corresponding to the duration in days that force was applied, i.e., 0, 1, 3, and 7 days. Stress were measured by cortisol levels, and inflammation were measured by interleukin-1 beta (IL-1β) levels in blood plasma.

Results: The VE group had lower cortisol levels than the control group, and significant found on days 3 and 7 (p = 0.026 and p = 0.037). The cortisol level in the VE group decreased faster, beginning on day 1, whilst the control group occurred on day 3. Statistical analysis of IL-1β levels found insignificant differences between the two groups.

Conclusion: Vitamin E helps reduce stress caused by orthodontic force due to tooth movement.

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Vitamin E and preterm infants

Tohru Ogihara, Makoto Mino

Free Radic Biol Med . 2021 Dec 3;S0891-5849(21)00845-5. doi: 10.1016/j.freeradbiomed.2021.11.037. Online ahead of print.


In evaluating vitamin E (VE) nutritional status of preterm infants, it is essential that any data should be compared with those of healthy term infants, and never with those of adults. Moreover, it should be evaluated in terms of gestational age (GA), not birth weight (BW), because placental transfer of most nutrients from mother to fetus is dependent on GA, not BW. Judging from the limited data during the last 75 years, there was no significant correlation between GA and VE concentrations in circulation or in the red blood cells (RBCs), leukocytes, and buccal mucosal cells. In addition, the oxidizability of polyunsaturated fatty acids (PUFAs) in plasma or RBCs, as targets for protection by VE chain-breaking ability, was lower in preterm infants. However, because of the minimal information available about hepatic VE levels, which is considered a key determinant of whole body VE status, the decision on whether VE status of preterm infants is comparable with that of term infants should be postponed. Clinical trials of VE supplementation in preterm infants were repeatedly undertaken to investigate whether VE reduces severity or inhibits development of several diseases specific to preterm infants, namely retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and germinal matrix hemorrhage – intraventricular hemorrhage (GMH-IVH). Most of these trials resulted in a misfire, with a few exceptions for IVH prevention. However, almost all these studies were performed from 1980s to early 1990s, in the pre-surfactant era, and the study populations were composed of mid-preterm infants with GAs of approximately 30 weeks (wks). There is considerable difference in ‘preterm infants’ between the pre- and post-surfactant eras; modern neonatal medicine mainly treats preterm infants of 28 wks GA or less. Therefore, these results are difficult to apply in modern neonatal care. Before considering new trials of VE supplementation, we should fully understand modern neonatal medicine, especially the recent method of oxygen supplementation. Additionally, a deeper understanding of recent progress in pathophysiology and therapies for possible target diseases is necessary to decide whether VE administration is still worth re-challenging in modern neonatal intensive care units (NICUs). In this review, we present recent concepts and therapeutic trends in ROP, BPD, and GMH-IVH for those unfamiliar with neonatal medicine. Numerous studies have reported the possible involvement of reactive oxygen species (ROS)-induced damage in relation to supplemental oxygen use, inflammation, and immature antioxidant defense in the development of both BPD and ROP. Various antioxidants effectively prevented the exacerbation of BPD and ROP in animal models. In the future, VE should be re-attempted as a complementary factor in combination with various therapies for BPD, ROP, and GMH-IVH. Because VE is a natural and safe supplement, we are certain that it will attract attention again in preterm medicine.

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Antioxidant and cytotoxicity activities of δ-tocotrienol from the seeds of Allophylus africanus

Jean Francois Zeutsop, Joviale Nouboudem Zébazé, Raymond Ngansop Nono, Marcel Frese, Jean Rodolphe Chouna, Bruno Ndjakou Lenta, Pépin Nkeng-Efouet-Alango, Norbert Sewald

Nat Prod Res . 2021 Dec 2;1-11. doi: 10.1080/14786419.2021.2010195. Online ahead of print.


Chemical investigation of Allophylus africanus P. Beauv fruits led to the isolation of a new δ-tocotrienol, 3α-hydroxy-δ-tocotrienol (1) together with eight known compounds (29). Compound (1) was allylated (1a) and prenylated (1 b and 1c) to give three new semi-synthesized derivatives which were fully characterized as: 6-O-allyl-3α-hydroxy-δ-tocotrienol (1a), 6-O-prenyl-3α-hydroxy-δ-tocotrienol (1 b) and 6-O,5-C-diprenyl-3α-hydroxy-δ-tocotrienol (1c). The structures of compounds were established using comprehensive spectroscopic analysis including UV, MS, 1 D NMR, 2 D NMR and by comparison with the corresponding literature data. Compound (1) and its semi-synthetic derivatives (1a-c) were tested for their antioxydant activity using DPPH radical scavenging assay and also for their cytotoxicity using human cervix carcinoma KB-3-1 cell lines. The results showed that compound (1) exhibited antioxidant activity with an IC50 value of 0.25 μM compared to the reference control trolox (26 µM); and good cytotoxic activity with IC50 values of 97 μM compared to the reference (+)-griseofulvin (IC50 between17-21 μM).

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Vitamin E research: Past, now and future

Regina Brigelius-Flohé

Free Radic Biol Med . 2021 Dec;177:381-390. doi: 10.1016/j.freeradbiomed.2021.10.029. Epub 2021 Oct 29.


The early history of vitamin E from its discovery by Herbert M. Evans and Katharine J. S. Bishop in 1922 up to its chemical synthesis by Paul Karrer and coworkers in 1938 and the development of the concept that vitamin E acts as an antioxidant in vivo are recalled. Some more recent results shedding doubt on this hypothesis are reviewed. They comprise influence of vitamin E on enzyme activities, signaling cascades, gene expression and bio-membrane structure. The overall conclusion is that our knowledge of the vitamin’s mechanism of action still remains fragmentary. The metabolism of tocopherols and tocotrienols is presented and discussed in respect to bioactivity of the metabolites, interference with drug metabolism and the future design of clinical trials. Some strategies are recommended how to reach the final goal: the identification of the primary vitamin E target(s) and the analysis of the downstream events up to the physiological phenomena.

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The use of vitamin E in preventing taxane-induced peripheral neuropathy

Muhammad Ali Heiba, Soheir Sayed Ismail, Mohamed Sabry, Walid Abd Elmoniem Bayoumy, Khaled Abdel-Aziz Kamal

Cancer Chemother Pharmacol . 2021 Dec;88(6):931-939. doi: 10.1007/s00280-021-04347-6. Epub 2021 Sep 1.


Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy. Several trials have evaluated the protective effect of vitamin E in preventing CIPN with controversial results. This study aims to outline the role of vitamin E in preventing CIPN.

Methods: A prospective phase II, open-label randomized controlled study was conducted in patients receiving taxane-based chemotherapy in Ain Shams University Hospitals, using vitamin E at a dose of 400 mg twice daily. The primary endpoint was the incidence of grade ≥ 2 sensory neuropathy according to CTCAE v 5.0 in each treatment arm. Secondary endpoints include time to onset and the duration of grade ≥ 2 sensory neuropathy.

Results: A total of 140 patients were randomized between the control and vitamin E arms. There was no difference in the incidence of grade ≥ 2 sensory neuropathy between the two arms (25.7% in each arm; P = 1.0), as well as the time to onset of neuropathy (P = 0.24). However, there was a statistically significant difference between the 2 arms as regards the duration of neuropathy. The median duration was 12.5 vs. 5 weeks in the control and vitamin E arms respectively (P = 0.01).

Conclusion: Our study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.

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