The role of Vitamin E in hip implant-related corrosion and toxicity: Initial outcome

Vikas Manjunath, Ravindra V Badhe, Maureen McCoy, Josiah Rynne, Aisha Bhatti, Abhijith Segu, Ebru Oral, Joshua J Jacobs, Paul Chastain, Divya Bijukumar, Mathew T Mathew

J Mech Behav Biomed Mater . 2021 Nov;123:104769. doi: 10.1016/j.jmbbm.2021.104769. Epub 2021 Aug 11.

Abstract

In orthopedic healthcare, Total Hip Replacement (THR) is a common and effective solution to hip-related bone and joint diseases/fracture; however, corrosion of the hip implant and the release of degradation metal ions/particles can lead to early implant failure and pose potential toxicity risk for the surrounding tissues. The main objective of this work was to investigate the potential role of Vitamin E to minimize corrosion-related concerns from CoCrMo hip implants. The study focused on two questions (i) Can Vitamin E inhibit CoCrMo corrosion? and (ii) Does Vitamin E moderate the toxicity associated with the CoCrMo implant particles? In the study (i) the electrochemical experiments (ASTM G61) with different concentrations of Vitamin E (1, 2, 3 mg/ml against the control) were performed using normal saline and simulated synovial fluid (Bovine calf serum-BCS, 30 g/L protein, pH 7.4) as electrolytes. The polished CoCrMo disc (Ra 50 nm) was the working electrode. The findings suggested that both Vitamin E-Saline (45 ± 0.9%) and Vitamin E-BCS (91 ± 3%) solutions protected against implant corrosion at a Vitamin E concentration of 3 mg/ml, but Vitamin E-BCS showed protection at all Vitamin E (1-3 mg/ml) concentration levels. These results suggested that the Vitamin E and the protein present in the BCS imparted additive effects towards the electrochemical inhibition. In the study (ii) the role of Vitamin E in cytotoxicity inhibition was studied using a mouse neuroblastoma cell line (N2a) for CoCrMo particles and Cr ions separately. The CoCrMo particles were generated from a custom-built hip simulator. The alamarBlue assay results suggested that Vitamin E provides significant protection (85% and 75% proliferation) to N2a cells against CoCrMo particles and Cr ions, respectively at 1 μg/ml concentration, as compared to the control group. However, the results obtained from ROS expression and DNA fiber staining suggest that Vitamin E is only effective against CoCrMo degradation particles and not against Cr ions. In summary, the findings show that Vitamin E can minimize the corrosion processes and play a role in minimizing the potential toxicity associated with implants.

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Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation

Shonia Subramaniam, Jeya Seela Anandha Rao, Premdass Ramdas, Mei Han Ng, Methil Kannan Kutty, Kanga Rani Selvaduray, Ammu Kutty Radhakrishnan

Clin Exp Immunol . 2021 Nov;206(2):161-172. doi: 10.1111/cei.13650. Epub 2021 Aug 18.

Abstract

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (Treg ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p < 0.05), CD8+ (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed Treg cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4+ T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.

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Effect of alpha-tocopherol and dose sensitivity on pancreatitis formation in rats with experimental pancreatitis

Deniz Tazeoğlu, Cüneyt Akyüz, Mehmet Gökçeimam, Gülçin Harman Kamalı, Ayhan Özsoy, Servet Rüştü Karahan

Ulus Travma Acil Cerrahi Derg . 2021 Nov;27(6):605-612. doi: 10.14744/tjtes.2020.89054.

Abstract

Background: Acute pancreatitis is an inflammatory disease accompanied by pancreatic inflammation characterized by acinar cell damage and leukocyte infiltration in the tissue. At present, mortality and morbidity rates are high despite the current treatment of pancreatitis; therefore, new studies and treatment studies are needed. In this study, the effects of alpha-tocopherol on different doses of L-arginine-induced experimental acute pancreatitis model were investigated.

Methods: Thirty adult male Sprague-Dawley albino rats were randomly divided into four groups; control (sham) group (n=6), acute pancreatitis group (n=8), low-dose alpha-tocopherol (200 mg/kg once intraperitoneal [IP]) group (n=8), and high dose alpha-tocopherol (400 mg/kg once ip) group (n=8). Experimental acute pancreatitis model was created by a single IP dose of 5 g/kg of L-arginine. Alpha-tocopherol was administered in a single dose intraperitoneally, 30 min before the creation of the experimental model of acute pancreatitis induced by L-arginine induction in Groups 3 and 4. Tissue and blood samples were taken under anesthesia 72 h after L-arginine injection; then the rats were sacrificed by decapitation. Serum amylase, lipase, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) levels were examined. Pancreatic tissue samples were examined under a light microscope for histopathological examination.

Results: When the acute pancreatitis group (Group 2) was compared to the control group (Group 1), serum amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP levels were all significantly increased (p<0.05 for all). Histopathological examination showed significant difference in edema (p<0.001) and inflammation (p=0.007) scores. When the low (Group 3) and high (Group 4) dose alpha-tocopherol groups were compared to Group 2, amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP parameters were statistically significantly lower (p<0.05 for all). In the histopathological comparison of Groups 2, 3, and 4, edema and inflammation scores were decreased in Groups 3 and 4 compared to Group 2. Comparing Group 4 to Group 3, lipase (p<0.01), IL-6 (p=0.038), and TNF-alpha (p=0.002) levels were significantly decreased; no significant difference was observed in the histopathological evaluation.

Conclusion: Alpha-tocopherol was found to reduce inflammation and pancreatic damage in acute pancreatitis and was more effective in high doses.

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Interweaving epilepsy and neurodegeneration: Vitamin E as a treatment approach

Aman B Upaganlawar, Nitu L Wankhede, Mayur B Kale, Mohit D Umare, Aayush Sehgal, Sukhbir Singh, Saurabh Bhatia, Ahmed Al-Harrasi, Agnieszka Najda, Renata Nurzyńska-Wierdak, Simona Bungau, Tapan Behl

Biomed Pharmacother . 2021 Nov;143:112146. doi: 10.1016/j.biopha.2021.112146. Epub 2021 Sep 8.

Abstract

Epilepsy is the most common neurological disorder, affecting nearly 50 million people worldwide. The condition can be manifested either due to genetic predisposition or acquired from acute insult which leads to alteration of cellular and molecular mechanisms. Evaluating the latest and the current knowledge in regard to the mechanisms underlying molecular and cellular alteration, hyperexcitability is a consequence of an imbalanced state wherein enhance excitatory glutamatergic and reduced inhibitory GABAergic signaling is considered to be accountable for seizures associated damage. However, neurodegeneration contributing to epileptogenesis has become increasingly appreciated. The components at the helm of neurodegenerative alterations during epileptogenesis include GABAergic neuronal and receptor changes, neuroinflammation, alteration in axonal transport, oxidative stress, excitotoxicity, and other cellular as well as functional changes. Targeting neurodegeneration with vitamin E as an antioxidant, anti-inflammatory and neuroprotective may prove to be one of the therapeutic approaches useful in managing epilepsy. In this review, we discuss and converse about the seizure-induced episodes as a link for the development of neurodegenerative and pathological consequences of epilepsy. We also put forth a summary of the potential intervention with vitamin E therapy in the management of epilepsy.

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Determination of tissue-specific interaction between vitamin C and vitamin E in vivo using senescence marker protein-30 knockout mice as a vitamin C synthesis deficiency model

Ayami Sato, Yuka Takino, Tomohiro Yano, Koji Fukui, Akihito Ishigami

SaveEmailSend to Display options full text links full text provider logo actions Cite Favorites share page navigation Title & authors Abstract Related information LinkOut - more resources Br J Nutr . 2021 Nov 2;1-33. doi: 10.1017/S0007114521004384. Online ahead of print.

Abstract

Vitamin E (α-tocopherol; VE) is known to be regenerated from VE radicals by vitamin C (L-ascorbic acid; VC) in vitro. However, their in vivo interaction in various tissues is still unclear. Therefore, we alternatively examined the in vivo interaction of VC and VE by measurement of their concentrations in various tissues of senescence marker protein-30 (SMP30) knockout (KO) mice as a VC synthesis deficiency model. Male SMP30-KO mice were divided into four groups (VC+/VE+, VC+/VE-, VC-/VE+, and VC-/VE-), fed diets with or without 500 mg/kg VE and given water with or without 1.5 g/L VC ad libitum. Then, VC and VE concentrations in the plasma and various tissues were determined. Further, gene expression levels of transporters associated with VC and VE, such as α-tocopherol transfer protein (α-TTP) and sodium-dependent vitamin C transporters (SVCTs), were examined. These results showed that the VE levels in the VC-depleted (VC-/VE+) group were significantly lower than those in the VC+/VE+ group in the liver and heart; the VC levels in the VE-depleted (VC+/VE-) group were significantly lower than those in the VC+/VE+ group in the kidneys. The α-TTP gene expression in the liver and kidneys were decreased by VC and/or VE depletion. Moreover, SVCT1 gene expression in the liver was decreased by both VC and VE depletion. In conclusion, these results indicate that VC spares VE mainly in the liver and heart, and that VE spares VC in the kidneys of SMP30-KO mice. Thus, interaction between VC and VE is likely to be tissue specific.

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Stress-activated leukocyte 12/15-lipoxygenase metabolite enhances struggle behaviour and tocotrienols relieve stress-induced behaviour alteration

Mototada Shichiri, Noriko Ishida, Yoshinori Aoki, Taisuke Koike, Yoshihisa Hagihara

Free Radic Biol Med . 2021 Nov 1;175:171-183. doi: 10.1016/j.freeradbiomed.2021.08.236. Epub 2021 Aug 30.

Abstract

Stress induces emotional arousal causing anxiety, irritability, exaggerated startle behaviour, and hypervigilance observed in patients with trauma and stress-related mental disorders, including acute stress disorder and post-traumatic stress disorder. Central norepinephrine release promotes stress-induced emotional arousal. However, the regulator of emotional arousal remains unknown. Here, we show that the arachidonate-derived metabolite produced by stress-activated leukocyte 12/15-lipoxygenase is remarkably elevated in the plasma and upregulates the central norepinephrine release, resulting in the enhancement of the struggle behaviour (= escape behaviour) in the tail suspension test. Struggle behaviour is mimicking a symptom of emotional arousal. This stress-induced struggle behaviour was absent in 12/15-lipoxygenase deficient mice; however, intravenous administration of a 12/15-lipoxygenase metabolite to these mice after stress exposure rekindled the struggle behaviour. Furthermore, tocotrienols and geranylgeraniol reduced stress-induced 12/15-lipoxygenase metabolite production and suppressed the struggle behaviour. Our findings indicate that arachidonate-derived 12/15-lipoxygenase metabolite is involved in the regulation of stress-enhanced central norepinephrine release and struggle behaviour. In addition, we propose 12/15-lipoxygenase as a potential therapeutic target for the treatment of emotional arousal observed in stress-related mental disorders.

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Reflections on a century of vitamin E research: Looking at the past with an eye on the future

Angelo Azzi

Free Radic Biol Med . 2021 Nov 1;175:155-160. doi: 10.1016/j.freeradbiomed.2021.07.042. Epub 2021 Sep 1.

Abstract

The name vitamin E, was given by Barnett and Sure who suggested that the factor proposed by Evans and Bishop as substance “X,” be termed vitamin “E” as the next vitamin after the A, B, C and D vitamins had been already described. The identification of vitamin E with a-tocopherol was made in 1936 by Evans’ group. One year later β-tocopherol and 11 years later δ-tocopherol were isolated. Tocotrienol (named zetatocopherol) was first described in 1957 and later isolated in 1961. The antioxidant property of tocopherols was reported by Olcott and Emerson in 1937. Inherited vitamin E deficiency, AVED, characterized by a form of neuromyopathy was first described in 1981. The disease, was localized to chromosome 8q and found to be caused by a mutation of the a-TTP gene. The subsequent paragraphs are not a comprehensive review but only critical reflections on some important aspects of vitamin E research.

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Diverse cytoprotective actions of vitamin E isoforms- role as peroxyl radical scavengers and complementary functions with selenoproteins

Yoshiro Saito

Free Radic Biol Med . 2021 Nov 1;175:121-129. doi: 10.1016/j.freeradbiomed.2021.08.234. Epub 2021 Sep 2.

Abstract

Vitamin E, a generic term for tocopherol (T) and tocotrienol (T3), is one of the most potent lipid-soluble antioxidants in the body. It is classified into T and T3 based on the difference in the side chain structure. T and T3 have four isoforms: α-, β-, γ-, and δ, which have different chroman rings. Both T and T3 exhibit a similar ability to scavenge free radicals, and the extent of this ability depends on the difference in the chroman structure. However, they display unique cytoprotective activities in cultured cells depending on the difference in the side chain structure. The cytoprotective effects of vitamin E have received much attention in the prevention of ferroptosis, which is a distinct form of cell death involving iron-dependent lipid peroxidation. This review focuses on the cytoprotective actions of vitamin E isoforms against oxidative stress, particularly the difference between T and T3 and its relation to cellular uptake and distribution. Moreover, the molecular mechanism for cytoprotection of vitamin E oxidation products is explained, and the complementary role of vitamin E and selenoproteins to prevent lipid peroxidation and ferroptosis is described. Furthermore, the evaluation of vitamin E’s radical scavenging activity in vivo using oxidative stress markers is discussed, particularly based on kinetic data and the physiological molar ratio of vitamin E to substrates, and the limited role of vitamin E as a peroxyl radical scavenger is described. The future directions and unresolved issues related to vitamin E and lipid peroxidation are also discussed.

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