Blog Archives

Vitamin E in the treatment of tardive dyskinesia: a meta-analysis

Hongyan Xu, Haoqiang Qin, Shaohua Chen, Mingjian Guan

Int Clin Psychopharmacol . 2022 Mar 1;37(2):60-66. doi: 10.1097/YIC.0000000000000387.

Abstract

Long-term use of antipsychotic drugs is associated with tardive dyskinesia. At present, there is no satisfactory treatment for tardive dyskinesia. Some randomized trials suggested that vitamin E can improve tardive dyskinesia. This study was undertaken to evaluate the effects of vitamin E treatment for tardive dyskinesia. We searched internet databases for randomized controlled trials. A total of 21 studies including 854 patients with tardive dyskinesia were included in this meta-analysis. Eighteen studies reported the Abnormal Involuntary Movements Scale (AIMS) as the primary outcome. After vitamin E treatment, a decrease of 2.36 (95% CI = -3.27 to -1.45; P < 0.00001) in the AIMS was observed in the treatment group, compared with the control group. Vitamin E may offer a new avenue treatment for tardive dyskinesia.

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Gamma-tocotrienol, a radiation countermeasure, reverses proteomic changes in serum following total-body gamma irradiation in mice

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

Sci Rep . 2022 Mar 1;12(1):3387. doi: 10.1038/s41598-022-07266-5.

Abstract

Radiological incidents or terrorist attacks would likely expose civilians and military personnel to high doses of ionizing radiation, leading to the development of acute radiation syndrome. We examined the effectiveness of prophylactic administration of a developmental radiation countermeasure, γ-tocotrienol (GT3), in a total-body irradiation (TBI) mouse model. CD2F1 mice received GT3 24 h prior to 11 Gy cobalt-60 gamma-irradiation. This dose of radiation induces severe hematopoietic acute radiation syndrome and moderate gastrointestinal injury. GT3 provided 100% protection, while the vehicle control group had 100% mortality. Two-dimensional differential in-gel electrophoresis was followed by mass spectrometry and Ingenuity Pathway Analysis (IPA). Analysis revealed a change in expression of 18 proteins in response to TBI, and these changes were reversed with prophylactic treatment of GT3. IPA revealed a network of associated proteins involved in cellular movement, immune cell trafficking, and inflammatory response. Of particular interest, significant expression changes in beta-2-glycoprotein 1, alpha-1-acid glycoprotein 1, alpha-2-macroglobulin, complement C3, mannose-binding protein C, and major urinary protein 6 were noted after TBI and reversed with GT3 treatment. This study reports the untargeted approach, the network, and specific serum proteins which could be translated as biomarkers of both radiation injury and protection by countermeasures.

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Oil-based vitamin E oral spray for oral health in pregnancy

Sabrina Reppuccia, Felice Crocetto, Elisabetta Gragnano, Pietro D'Alessandro, Martin Vetrella, Gabriele Saccone, Bruno Arduino

Future Sci OA . 2022 Mar 1;8(4):FSO790. doi: 10.2144/fsoa-2021-0095. eCollection 2022 Apr.

Abstract

Aim: To assess the efficacy of vitamin E oral spray in pregnancy.

Materials & methods: This was a retrospective study aimed to evaluate efficacy of vitamin E oral spray (vitamin E acetate in a medium chain tryglicerides vehicle – patented formulation) starting from the first trimester of pregnancy, with a control group.

Results: A total of 100 women were included in the study and were compared with a matched control group. Only 25/200 women reported to have at least one teeth cleaning during pregnancy. Women who received the oral spray had a significantly lower risk of preterm birth compared with the control group, and lower risk of periodontal diseases.

Conclusion: Use of oil-based vitamin E oral spray in pregnancy is associated with a decreased risk of periodontal diseases and therefore preterm birth.

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A Redox-Silent Analogue of Tocotrienol May Break the Homeostasis of Proteasomes in Human Malignant Mesothelioma Cells by Inhibiting STAT3 and NRF1

Kyota Ishii, Momoka Fusegi, Tatsuki Mori, Kosuke Teshima, Nanako Ninomiya, Kakeru Kohno, Ayami Sato, Tatsuya Ishida, Yuichi Miyakoshi, Tomohiro Yano

Int J Mol Sci . 2022 Feb 28;23(5):2655. doi: 10.3390/ijms23052655.

Abstract

6-O-Carboxypropyl-alpha-tocotrienol (α-T3E) is a multi-target redox-silent analogue of tocotrienol that exhibits cytotoxicity against many cancer cells, including malignant mesothelioma (MM) cells. α-T3E has several molecular targets to effectively induce cytotoxicity against MM cells; however, the mechanisms underlying this cytotoxicity remain unclear. In the present study, we demonstrated that the α-T3E-dependent disruption of the homeostasis of proteasomes strongly induced endoplasmic reticulum (ER) stress, which resulted in effective cytotoxicity against MM cells. The α-T3E-dependent disruption of the homeostasis of proteasomes depended on decreases in proteasome subunits via the inactivation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid 2 related factor-1 (NRF1), which inhibited protease activity, such as chymotrypsin-like activity, in proteasomes. The α-T3E-dependent inhibition of this activity also induced severe ER stress and ultimately resulted in effective cytotoxicity against MM cells with chemoresistance. The present results indicate that α-T3E acts as an effective anti-mesothelioma agent by disrupting the homeostasis of proteasomes through the simultaneous inactivation of STAT3 and NRF1.

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Potential of the Compounds from Bixa orellana Purified Annatto Oil and Its Granules (Chronic ®) against Dyslipidemia and Inflammatory Diseases: In Silico Studies with Geranylgeraniol and Tocotrienols

Mateus Alves Batista, Abrahão Victor Tavares de Lima Teixeira Dos Santos, Aline Lopes do Nascimento, Luiz Fernando Moreira, Indira Ramos Senna Souza, Heitor Ribeiro da Silva, Arlindo César Matias Pereira, Lorane Izabel da Silva Hage-Melim, José Carlos Tavares Carvalho

Molecules . 2022 Feb 28;27(5):1584. doi: 10.3390/molecules27051584.

Abstract

Some significant compounds present in annatto are geranylgeraniol and tocotrienols. These compounds have beneficial effects against hyperlipidemia and chronic diseases, where oxidative stress and inflammation are present, but the exact mechanism of action of such activities is still a subject of research. This study aimed to evaluate possible mechanisms of action that could be underlying the activities of these molecules. For this, in silico approaches such as ligand topology (PASS and SEA servers) and molecular docking with the software GOLD were used. Additionally, we screened some pharmacokinetic and toxicological parameters using the servers PreADMET, SwissADME, and ProTox-II. The results corroborate the antidyslipidemia and anti-inflammatory activities of geranylgeraniol and tocotrienols. Notably, some new mechanisms of action were predicted to be potentially underlying the activities of these compounds, including inhibition of squalene monooxygenase, lanosterol synthase, and phospholipase A2. These results give new insight into new mechanisms of action involved in these molecules from annatto and Chronic®.

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Drug release, stability and efficiency of vitamin e loaded in liposomes for bovine sperm protection in cryopreservation medium

L Taouzinet, S Fatmi, A Khellouf, M Lahianl-Skiba, M Skiba, M Iguer-Ouada

Cryo Letters . Jan-Feb 2022;43(1):50-57.

Abstract

Background: It is known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability. The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase both dissolution and absorption because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, several drawbacks have been reported, the most common is liposome structural instability.

Objective: To encapsulate alpha tocopherol into liposomes, to determine the new formulation stability and to study the drug-release of alpha tocopherol into the sperm cryopreservation medium.

Materials and methods: The liposomes prepared by an ethanol injection method were characterized for size stability, alpha tocopherol release and sperm motility tests.

Results: The prepared unilamellar vesicles had both narrow size distribution (around 99 nm) and a good physical and chemical stability at 4°C during 12 months. The liposomes did not release the vitamin E immediately, but retained the protectant for 24 hours, probably due to the rigidity of the liposomal fence which was reinforced by adding cholesterol. Then, all vitamin E molecules were released by 48 hours. Release was potentially by Fickian diffusion probably by the creation of mini-ducts due to both agitation and fence hydration. Moreover, semen motility treated with vitamin E liposome preparations was significantly improved compared to all other treatments (including commonly used sperm conservation media).

Conclusion: The stable vitamin E liposomes formulated in this work are a promising alternative for semen cryopreservation protection.

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A 28-year prospective analysis of serum vitamin E, vitamin E-related genetic variation and risk of prostate cancer

Wayne R Lawrence, Jung-Eun Lim, Jiaqi Huang, Stephanie J Weinstein, Satu Mӓnnistӧ, Demetrius Albanes

Prostate Cancer Prostatic Dis . 2022 Feb 23. doi: 10.1038/s41391-022-00511-y. Online ahead of print.

Abstract

Objective: Investigate the relationship between serum α-tocopherol concentration and long-term risk of prostate cancer, and evaluate the interaction with vitamin E-related genetic variants and their polygenic risk score (PRS).

Methods: We conducted a biochemical analysis of 29,102 male Finnish smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and 2724 prostate cancer cases were identified during 28 years of follow-up. Cox proportional hazards models examined whether serum α-tocopherol concentrations were associated with prostate cancer risk. Among 8383 participants, three SNPs related to vitamin E status (rs964184, rs2108622, and rs11057830) were examined to determine whether they modified the relationship between serum α-tocopherol concentrations and prostate cancer risk, both individually and as a PRS using logistic regression models.

Results: No association was observed between serum α-tocopherol and prostate cancer risk (fifth quintile (Q5) vs. Q1 hazard ratio (HR) = 0.87, 95% confidence interval (95% CI) 0.75, 1.02; P-trend = 0.57). Though no interactions were seen by population characteristics, high α-tocopherol concentration was associated with reduced prostate cancer risk among the trial α-tocopherol supplementation group (Q5 quintile vs. Q1 HR = 0.79, 95% CI 0.64, 0.99). Finally, no associated interaction between the three SNPs or their PRS and prostate cancer risk was observed.

Conclusion: Although there was a weak inverse association between α-tocopherol concentration and prostate cancer risk over nearly three decades, our findings suggest that men receiving the trial α-tocopherol supplementation who had higher baseline serum α-tocopherol concentration experienced reduced prostate cancer risk. Vitamin E-related genotypes did not modify the serum α-tocopherol-prostate cancer risk association.

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δ-Tocotrienol is the most potent vitamin E form in inhibiting prostate cancer cell growth and inhibits prostate carcinogenesis in Ptenp-/- mice

Hong Wang, William Yan, Yuhai Sun, Chung S Yang

Cancer Prev Res (Phila) . 2022 Feb 10;canprevres.0508.2021. doi: 10.1158/1940-6207.CAPR-21-0508. Online ahead of print.

Abstract

Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate specific Pten-/- (Ptenp-/-) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp-/- mice, which was confirmed by immunohistochemistry. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis.

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Tocoheal: All-in-one dressings with vitamin E tocotrienols

Globally, there are 8.1 million people who have wounds with or without infection. Rising wound incidence has imposed substantial burdens on healthcare expenditure. Despite being a common presentation in the clinical setting, providing optimal wound care remains a challenge. Normal acute wounds in healthy individuals tend to resolve spontaneously without clinical intervention. However, improper wound care may lead to undesirable complications such as wound infections or abnormal wound healing, resulting in uneven scar tissue formation. Affordable wound treatments that improve wound healing outcomes are desirable and beneficial to patients and the overall healthcare system.

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α-Tocopherol Prevents Sperm Apoptosis and Necrosis in Rats Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Dewa Ketut Meles, Kadek Rachmawati, Iwan Sahrial Hamid, Imam Mustofa, Wurlina Wurlina, Niluh Suwasanti, Desak Ketut Sekar Cempaka Putri, Suzanita Utama

Vet Med Int . 2022 Feb 21;2022:3685686. doi: 10.1155/2022/3685686. eCollection 2022.

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant that induces overproduction of reactive oxygen species (ROS). Studies on avoiding the adverse effects of dioxin pollution exposure are needed in all aspects, including reproductive health. This study aimed to determine the effect of α-tocopherol on superoxide dismutase (SOD) and malondialdehyde (MDA) levels, live spermatozoa, apoptosis, and necrosis in male rats exposed to dioxin as a model. Thirty healthy 12-week-old male rats were randomly divided into five groups. Rats in the control group were given corn oil twice daily at 4-hour intervals. The remaining rats were given TCDD 700 mg/kg BW daily, followed by administration of corn oil and α-tocopherol at doses of 77, 140, and 259 mg/kg BW/d for T0, T1, T2, and T3 groups, respectively. The treatments were conducted for 45 days; all rats were euthanized to collect blood and testicular samples on day 46. The results showed that exposure of TCDD resulted in a decrease in SOD activity and live spermatozoa and increased MDA level and death, apoptosis, and necrosis of spermatozoa (T0) compared to the control (C) group (p < 0.05). The administration of α-tocopherol, starting from the doses of 77 (T1), 149 (T2), and 259 mg (T3) per kg BW, was sequentially followed by returning MDA levels, recovering SOD activities, and restoration in the percentage of living, dead, apoptotic, and necrotic spermatozoa, similar (p > 0.05) to those of the control group. It could be concluded that the administration of α-tocopherol resolves the harmful effects of TCDD on the viability of spermatozoa in rats as a model.

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