Efficacy of water-based vitamin E solution versus placebo in the prevention of retinopathy of prematurity in very low birth weight infants: A randomized clinical trial

Silvia Romero-Maldonado, Araceli Montoya-Estrada, Enrique Reyes-Muñoz, Alberto Martín Guzmán-Grenfell, Yessica Dorin Torres-Ramos, Mario David Sánchez-Mendez, Maricruz Tolentino-Dolores, Manuel Bernardo Salgado-Valladares, Aurora Belmont-Gómez, Nayelli Najéra, Guillermo Ceballos, Jorge Arturo Cardona-Pérez, Juan José Hicks, Javier Mancilla-Ramírez

Medicine (Baltimore) . 2021 Aug 6;100(31):e26765. doi: 10.1097/MD.0000000000026765.

Abstract

Background:: Vitamin E has antioxidant properties, which help in scavenging free radicals, thereby reducing oxidation of lipids and proteins. This study aims to evaluate the efficacy of oral vitamin E supplementation in preventing retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) and decreasing oxidative stress 15 and 28 days post-intervention.

Methods:: Ninety VLBW infants were randomly assigned to two groups:

 

  1. 1.Treatment (treatment group (T), n = 48) or
  2. 2.Placebo (control group (C), n = 42).

 

Each group received 25 IU of vitamin E (T) or placebo (C).

Results:: The incidence of ROP in groups T and C was 12.5% (n=6) and 31% (n = 13), respectively (RR: 0.40; 95% CI: 0.10–0.96). There were no differences in mortality between groups. As expected, the vitamin E concentration was significantly increased 28 days post-intervention in group T.

Conclusion:: Oral supplementation with vitamin E may effectively prevent ROP development in VLBW infants with RDS. Oxidative damage markers were significantly lower, whereas total antioxidant capacity was increased in group T. However, levels of other antioxidants as vitamin A and C were not measured in two groups.

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Supplementation of antihypertensive drug regimen with vitamin E ameliorates alterations of primary haemodynamic parameters and total antioxidant capacity in ovariectomised rats

Temitayo Olabisi Ajibade, Foluso B Bolaji-Alabi, Ademola Adetokunbo Oyagbemi, Ifeoluwa W Ajileye, Temidayo Olutayo Omobowale

J Basic Clin Physiol Pharmacol . 2021 Aug 6. doi: 10.1515/jbcpp-2020-0097. Online ahead of print.

Abstract

Objectives: Ovariectomy induces heightened response to vasoconstrictors, alters vasorelaxation and consequently causes hypertension due to increased oxidative stress in rats.

Methods: This study evaluated the ameliorative effects of ramipril and vitamin E, on primary haemodynamic parameters and cardiac antioxidant defence status, in ovariectomised rats using 64 adult female rats of the Wistar strain randomly divided as follows: Control (sham); Ovariectomised (OVX); OVX plus Ramipril; OVX plus vitamin E; and OVX plus Ramipril plus vitamin E.

Results: The plasma level of oestrogen was significantly lower (p<0.05), in the ovariectomised rats compared with the sham. The systolic, diastolic and mean arterial blood pressure of ovariectomised rats increased significantly (p<0.05), but the alteration was significantly reduced by the administration of ramipril alone or in combination with vitamin E. Significant decrease (p<0.05) was observed in the serum level of nitric oxide in OVX group compared with Sham. Also, analysed markers of oxidative stress: Malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generated decreased significantly (p<0.05), but systemic antioxidants: reduced glutathione (GSH) contents; glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities increased significantly (p<0.05) in the ovariectomised rats treated with ramipril and vitamin E compared with untreated ovariectomised rats. The study concludes that alteration, in the primary haemodynamic parameters, associated with ovariectomy in rats is potently ameliorated by co-administration of the antihypertensive drug ramipril and vitamin E.

Conclusions: The supplementation of antihypertensive regimen with antioxidants such as vitamin E in the treatment of hypertension is therefore justifiable especially in ovariectomised or hypogonadal patients.

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Effects of Co-administration of Vitamin E and Lithium Chloride on Chronic Constriction Injury-induced Neuropathy in Male Wistar Rats: Focus on antioxidant and anti-inflammatory mechanisms

Kingsley Dominic Esu, Ahmed Olalekan Bakare, Bamidele Victor Owoyele

Pain Pract . 2021 Aug 5. doi: 10.1111/papr.13064. Online ahead of print.

Abstract

Objectives: This study investigated the antinociceptive effects of co-administration of lithium chloride (LiCl) and vitamin E (Vit. E) on chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. It further explored the anti-inflammatory and neuroprotective properties of LiCl and Vit. E which may be complementary to the antinociceptive effects of the two substances.

Methods: Thirty-six male Wistar rats, 190.00 ± 10.00 g of body weight (b.w) were randomly assigned to six experimental groups and administered with either normal saline, Vit. E, LiCl, or their combination, once daily for twenty-one (21) days. CCI was used to induce NP and mechanical allodynia was assessed using von Frey filaments and pinprick test. Open field maze (OFM) was used to assess the exploratory behaviour. Biochemical parameters were assessed in the dorsal root ganglion (DRG) after twenty-one days of treatment.

Results: Mechanical allodynia was developed in rats following CCI. Co-administration of LiCl and Vit.E. synergistically reduced mechanical hyperalgesia in rats which were significantly different compared with the single administration of either Vit.E. or LiCl. Combined doses of Vit.E. and LiCl significantly increases the explorative behaviour in the OFM. CCI increased malondialdehyde (MDA), tumour necrotic factor-alpha (TNF-α), calcitonin gene-related polypeptide (CGRP), calcium ion (Ca2+ ), and reduced superoxide dismutase (SOD) activities. Co-administration of LiCl and Vit.E. significantly reduced MDA, TNF-α, but increased SOD compared with ligated control.

Discussion: The findings revealed that the synergistic effects of the co-administration of Vit. E and LiCl in ameliorating neuropathic pain are mediated by their anti-inflammatory and antioxidant properties.

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Vitamin E Toxicity

Kristen N. Owen, Olga Dewald

In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. 2021 Aug 1.

Excerpt

Vitamin E is a major lipid-soluble antioxidant obtained exclusively from the diet. It was discovered in the 1920s as an essential dietary element required by rats for reproduction. There are approximately eight different vitamin E-related molecules, but the dominant molecule in humans is alpha-tocopherol. Tocotrienols are the other molecules that are widely studied for vitamin E supplementation. These two molecules have been studied in various dosages and for many different health purposes. Vitamin E has peroxyl radical scavenger properties. While vitamin E toxicity is associated with an increased risk of bleeding, its deficiency has been associated with neurologic diseases and anemia.

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Vitamin E Can Ameliorate Oxidative Damage of Ovine Hepatocytes In Vitro by Regulating Genes Expression Associated with Apoptosis and Pyroptosis, but Not Ferroptosis

Luyang Jian, Ying Xue, Yuefeng Gao, Bo Wang, Yanghua Qu, Shuanghong Li, Heqiong Li, Zhen Li, Bing Wang, Hailing Luo

Molecules . 2021 Jul 27;26(15):4520. doi: 10.3390/molecules26154520.

Abstract

(1) Background: the current research was conducted to investigate the potential non-antioxidant roles of vitamin E in the protection of hepatocysts from oxidative damage. (2) Methods: primary sheep hepatocytes were cultured and exposed to 200, 400, 600, or 800 μmol/L hydrogen peroxide, while their viability was assessed using a CCK-8 kit. Then, cells were treated with 400 μmol/L hydrogen peroxide following a pretreatment with 50, 100, 200, 400, and 800 μmol/L vitamin E and their intracellular ROS levels were determined by means of the DCF-DA assay. RNA-seq, verified by qRT-PCR, was conducted thereafter: non-treated control (C1); cells treated with 400 μmol/L hydrogen peroxide (C2); and C2 plus a pretreatment with 100 μmol/L vitamin E (T1). (3) Results: the 200-800 μmol/L hydrogen peroxide caused significant cell death, while 50, 100, and 200 μmol/L vitamin E pretreatment significantly improved the survival rate of hepatocytes. ROS content in the cells pretreated with vitamin E was significantly lower than that in the control group and hydrogen-peroxide-treated group, especially in those pretreated with 100 μmol/L vitamin E. The differentially expressed genes (DEGs) concerning cell death involved in apoptosis (RIPK1TLR7CASP8, and CASP8AP2), pyroptosis (NLRP3IL-1β, and IRAK2), and ferroptosis (TFRC and PTGS2). The abundances of IL-1βIRAK2NLRP3CASP8CASP8AP2RIPK1, and TLR7 were significantly increased in the C1 group and decreased in T1 group, while TFRC and PTGS2 were increased in T1 group. (4) Conclusions: oxidative stress induced by hydrogen peroxide caused cellular damage and death in sheep hepatocytes. Pretreatment with vitamin E effectively reduced intracellular ROS levels and protected the hepatocytes from cell death by regulating gene expression associated with apoptosis (RIPK1TLR7CASP8, and CASP8AP2) and pyroptosis (NLRP3IL-1β, and IRAK2), but not ferroptosis (TFRC and PTGS2).

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Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials

Ban-Hock Khor, Hui-Ci Tiong, Shing Cheng Tan, Sok Kuan Wong, Kok-Yong Chin, Tilakavati Karupaiah, Soelaiman Ima-Nirwana, Abdul Halim Abdul Gafor

PLoS One . 2021 Jul 23;16(7):e0255205. doi: 10.1371/journal.pone.0255205. eCollection 2021.

Abstract

Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 μmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 μmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.

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Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation

Martin Alcala, Victoria E Bolado, Isabel Sánchez-Vera, Sonia Clapés, Francisco Dasí, Guillermo Sáez, Esther Carrera, Fabiola Alvarez-Gallego, Mary R Loeken, Marta Viana

Antioxidants (Basel) . 2021 Jul 23;10(8):1173. doi: 10.3390/antiox10081173.

Abstract

Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma-glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation.

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GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis

Qian Hu, Yifan Zhang, Huiling Lou, Zexian Ou, Jin Liu, Wentao Duan, Hao Wang, Yuanlong Ge, Junxia Min, Fudi Wang, Zhenyu Ju

Cell Death Dis . 2021 Jul 15;12(7):706. doi: 10.1038/s41419-021-04008-9.

Abstract

Ferroptosis, a newly defined mode of regulated cell death caused by unbalanced lipid redox metabolism, is implicated in various tissue injuries and tumorigenesis. However, the role of ferroptosis in stem cells has not yet been investigated. Glutathione peroxidase 4 (GPX4) is a critical suppressor of lipid peroxidation and ferroptosis. Here, we study the function of GPX4 and ferroptosis in hematopoietic stem and progenitor cells (HSPCs) in mice with Gpx4 deficiency in the hematopoietic system. We find that Gpx4 deletion solely in the hematopoietic system has no significant effect on the number and function of HSPCs in mice. Notably, hematopoietic stem cells (HSCs) and hematopoietic progenitor cells lacking Gpx4 accumulated lipid peroxidation and underwent ferroptosis in vitro. α-Tocopherol, the main component of vitamin E, was shown to rescue the Gpx4-deficient HSPCs from ferroptosis in vitro. When Gpx4 knockout mice were fed a vitamin E-depleted diet, a reduced number of HSPCs and impaired function of HSCs were found. Furthermore, increased levels of lipid peroxidation and cell death indicated that HSPCs undergo ferroptosis. Collectively, we demonstrate that GPX4 and vitamin E cooperatively maintain lipid redox balance and prevent ferroptosis in HSPCs.

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Environmentally friendly achiote seed extracts with higher δ-tocotrienol content have higher in vitro and in vivo antioxidant activity than the conventional extract

Darío R Gómez-Linton, Arturo Navarro-Ocaña, Angélica Román-Guerrero, Silvestre Alavez, Luis Pinzón-López, José A Mendoza-Espinoza, Laura J Pérez-Flores

J Food Sci Technol . 2021 Jul;58(7):2579-2588. doi: 10.1007/s13197-020-04764-0. Epub 2020 Oct 2.

Abstract

Achiote (Bixa orellana) is highly appreciated as a condiment and as the main source of bixin and tocotrienols, both having antioxidant properties. To explore the possibility of maximizing the antioxidant activity of achiote seed extracts using clean methodologies, the use of sonication and green solvents were tested. Ethyl lactate, isopropyl acetate, and ethanol combined with probe sonication produced the best results, obtaining similar bixin contents but higher δ-tocotrienol contents, as well as significantly higher in vitro and in vivo antioxidant activity compared with the maceration method extract, requiring low energy and saving time and solvents. The probe-sonicated achiote extract with the highest δ-tocotrienol content was better at increasing the Caenorhabditis elegans resistance to oxidative stress than the extract obtained through maceration. This is the first report about the effect of sonication combined with green solvents on the bixin and δ-tocotrienol content in achiote seed extracts and its relevance on the in vitro and in vivo antioxidant activity.

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Efficacy of vitamin E in protection against methotrexate induced placental injury in albino rats

Sara Mohamed Naguib Abdel Hafez, Eman Elbassuoni, Walaa Yehia Abdelzaher, Nermeen N Welson, Gaber El-Saber Batiha, Khalid J Alzahrani, Fatma Alzhraa Fouad Abdelbaky

Biomed Pharmacother . 2021 Jul;139:111637. doi: 10.1016/j.biopha.2021.111637. Epub 2021 May 6.

Abstract

Methotrexate (MXT) is a chemotherapeutic drug that has been used in a wide range of clinical practices. Unfortunately, the administration of MXT during pregnancy may induce abortion, fetal deformities, and intrauterine growth retardation. Vitamin E is an antioxidant agent that can ameliorate free radical damage. The current work aimed to shed more light on the possible protective effect of vitamin E against MXT induced placental toxicity and to determine the possible mechanisms; biochemically, histologically, and immunohistochemically. Four groups were used: control pregnant, Vitamin E (VIT E) pregnant, Methotrexate (MXT) pregnant, and Vitamin E Methotrexate (VIT E-MXT) pregnant. The placental tissues were processed for light, immunohistochemical, and electron microscopic study. Other samples were obtained for biochemical study; the placental oxidant/antioxidant status was evaluated. The results showed that MXT caused various placental morphological changes in the form of distorted chorionic projection with an accumulation of hemosiderin granules in the trophoblastic cells. Maternal blood vessels showed a homogenous acidophilic material Edema of the extra-embryonic fetal membranes was noticed. A significant decreased in placental weight as well as increase in the oxidative and inflammatory markers were detected. Increased COX2 and decreased eNOS expressions were observed in the MXT group if compared to the control group. VIT E significantly restored the normal histological and immunohistochemical appearance, placental weight, and oxidant/antioxidant balance. It could be concluded the biochemical, morphological, and morphometric findings suggested that vitamin E coadministration is promising in attenuating the placental toxic effect of methotrexate. In this study, VIT E decreased the inflammatory and oxidative stress effect of methotrexate on the placental tissue by enhancing the level of eNOS.

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