Potential roles of vitamin E in age-related changes in skeletal muscle health.

Chung E, Mo H, Wang S, Zu Y, Elfakhani M, Rios SR, Chyu MC, Yang RS, Shen CL

Nutr Res. 2018 Jan;49:23-36. doi: 10.1016/j.nutres.2017.09.005. Epub 2017 Sep 21.

Abstract

Skeletal muscle disorders including sarcopenia are prevalent during the complex biological process of aging. Loss of muscle mass and strength commonly seen in sarcopenia is induced by impaired neuromuscular innervation, transition of skeletal muscle fiber type, and reduced muscle regenerative capacity, all attributable to chronic inflammation, oxidative stress, and mitochondrial dysfunction. Current literature suggests that vitamin E molecules (α-, β-, γ-, δ-tocopherols and the corresponding tocotrienols) with their antioxidant and anti-inflammatory capabilities may mitigate age-associated skeletal dysfunction and enhance muscle regeneration, thus attenuating sarcopenia. Preclinical and human experimental studies show that vitamin E benefits myoblast proliferation, differentiation, survival, membrane repair, mitochondrial efficiency, muscle mass, muscle contractile properties, and exercise capacity. Limited number of human cross-sectional observational studies reveal positive associations between serum tocopherol level and muscle strength. Several factors, including difficulties in validating vitamin E intake and deficiency, variations in muscle-protective activity and metabolism of diverse forms of vitamin E, and lack of understanding of the mechanisms of action, preclude randomized clinical trials of vitamin E in people with sarcopenia. Future research should consider long-term clinical trials of with adequate sample size, advanced imaging technology and omics approaches to investigate underlying mechanisms and assess clinically meaningful parameters such as muscle strength, physical performance, and muscle mass in sarcopenia prevention and/or treatment.

Guo Q, Wang J

Immunopharmacol Immunotoxicol. 2018 Jan 22:1-5. doi: 10.1080/08923973.2018.1424898. [Epub ahead of print]

Abstract

BACKGROUND:

The objective of this study is to investigate the effect of combination of umbilical cord-derived mesenchymal stem cell (UC-MSC) and vitamin E (VitE) on inflammation in mice with acute kidney injury (AKI).

METHODS:

UC-MSCs were isolated from pregnant wistar mice and cultured. A total of 90 female wistar mice were randomly divided into control group, AKI group, AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC group (18 mice in each group) which were given no treatment, normal saline, VitE, UC-MSC, and VitE + UC-MSC, respectively. The renal pedicles on both sides were clipped for 50 min with micro-artery clips to induce AKI. Six mice were sacrificed at days 1, 3, and 7, while blood and kidney tissues were collected to detect levels of blood urea nitrogen (BUN) and creatinine (Scr). Kidney tissues were stained by HE staining to observe pathological changes; levels of interleukin-lβ, TNF-α, interleukin-10, and β-FGF were measured by ELISA.

RESULTS:

Compared with the control group, AKI mice showed higher levels of serum BUN and Scr, tubular swelling and necrosis suggesting that AKI model was successfully established. Mice in AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC presented better renal function than mice of AKI group. Mice from AKI + VitE + UC-MSC group showed the best renal function with the least renal tubular injury (p < .05). ELISA detection revealed that pro-inflammatory cytokines were significantly increased and anti-inflammatory cytokine levels were significantly decreased in all time points (p < .05). VitE, UC-MSC, and VitE + UC-MSC resulted in the increase of anti-inflammatory cytokine levels and reduction of pro-inflammatory cytokine levels and the combination of VitE and UC-MSC performed favorable effect in the suppression of inflammation in AKI mice (p < .05).

CONCLUSIONS:

Combination of UC-MSC and VitE significantly inhibited inflammatory reaction in kidney through the regulation of inflammatory cytokines in the microenvironment of kidney with AKI. Combination of UC-MSC and VitE presented therapeutic effect on AKI than the single use of UC-MSC or VitE.

Yan X, Liu Y, Xie T, Liu F

Immunopharmacol Immunotoxicol. 2018 Jan 19:1-7. doi: 10.1080/08923973.2018.1424901. [Epub ahead of print]

Abstract

CONTEXT:

Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co²⁺) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.

OBJECTIVE:

We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co²⁺ and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.

METHODS:

To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10 μM α-tocopherol for 24 h. The cells were then exposed to different concentrations of CoNPs and Co²⁺ for 12 h, 24 h and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured.

RESULTS:

CoNPs and Co²⁺ can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co²⁺, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co²⁺ in vitro.

CONCLUSIONS:

Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.

Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP

Drug Discov Today. 2017 Dec;22(12):1765-1781. doi: 10.1016/j.drudis.2017.08.001. Epub 2017 Aug 5.

Abstract

Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.

Ibrahim FM, Attia HN, Maklad YA, Ahmed KA, Ramadan MF.

Pharm Biol. 2017 Dec;55(1):740-748. doi: 10.1080/13880209.2016.1275705.

Abstract

Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties. Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO. Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, and via oral gavage given indomethacin (10 mg/kg) or CPO (400 mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened. Results shown amounts of α-, β-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177 mg/kg oil, respectively. In COO, α, β, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, β-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6 mg GAE/g, respectively. Acute toxicity test determined that 400 mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10 mg/kg) or CLO (400 mg/kg) induced a significant (p < 0.05) reduction by 31.3 and 27.4%, respectively, in rat paw oedema as compared with the carrageenan-treated group. Indomethacin induced a significant ulcerogenic effect with an ulcer index of 19. Oral treatment of CPO showed no ulcerogenic effect, wherein no histopathological changes were observed. In conclusion, CPO, particularly CLO, could minimize acute inflammation.

Mâncio RD, Hermes TA, Macedo AB, Mizobuti DS, Valduga AH, Rupcic IF, Minatel E

Nutrition. 2017 Nov - Dec;43-44:39-46. doi: 10.1016/j.nut.2017.07.003.

Abstract

OBJECTIVE:

Oxidative stress, in addition to the absence of the dystrophin protein, has been considered an important regulator of Duchenne muscular dystrophy (DMD). Vitamin E presents an important role as a potent antioxidant and in preserving the integrity of the cell membrane. In this study, we evaluated the effects of vitamin E therapy on some physiological pathways that can contribute to muscle injury in the diaphragm muscle of mdx mice (the experimental model of DMD) such as CK levels, inflammatory response, oxidative stress, and the enzymatic antioxidant system.

METHODS:

Mdx mice (14 d old) received 40 mg vitamin E/kg daily by oral gavage for 14 d, followed by the removal of the diaphragm muscle. Control mdx mice and C57BL/10 mice received saline only for the same period and were used as controls.

RESULTS:

Vitamin E reduced the muscle fiber damage, oxidative stress, and inflammation process in the diaphragm muscle of mdx mice.

CONCLUSIONS:

Vitamin E improves skeletal muscle injury in mdx mice, promoting membrane repair and exhibiting antioxidant and antiinflammatory effects. These vitamin E effects suggest that this antioxidant therapy may be a relevant approach for dystrophinopathies.

Osipiani B, Machavariani T, Gvamichava T, Gachechiladze I, Nikobadze E

Georgian Med News. 2017 Oct;(271):102-106.

Abstract

It is commonly known that in diabetes mellitus the risk of cardiovascular diseases and mortality increases. The purpose of this study was to determine the specific features of the morphological restructuring of the myocardium in the early stage of experimental diabetes and use the combined impact of powerful antioxidants (Vitamin C and Vitamin E) on the rat myocardium in conditions of alloxan-induced diabetes. The experimental animals were divided into three groups: 40 rats were the target, and 20 rats were the control. Target rats were divided into 2 groups: 1) group consisted of 20 rats with alloxan-induced diabetes; 2) group of 20 rats, which after confirmation of alloxan-induced diabetes, during 4 weeks were given intramuscularly vitamins C and E. The material was studied by histological and electron microscopic methods of investigation In the early stage of DM development, structural alterations in the cardiomyocytes and microcirculatory channels can be observed in the heart. Aggregation and agglutination of red blood cells and endothelial cell destruction were found in some vessels. In the study the result of combined therapy of Vitamin C and Vitamin E is a decrease in blood glucose levels, increases of endothelial proliferation, promoting the formation of new capillaries and further reduction of the structural changes of cardiomyocytes. Apperently through its antioxidative and anti-inflammatory activity Vitamins C and E stabilizes the metabolism processes in the vascular system and consequently, improvement of the organ function.

Allen L, Ramalingam L, Menikdiwela K, Scoggin S, Shen CL, Tomison MD, Kaur G, Dufour JM, Chung E, Kalupahana NS, Moustaid-Moussa N

J Nutr Biochem. 2017 Oct;48:128-137. doi: 10.1016/j.jnutbio.2017.07.003. Epub 2017 Jul 10.

Abstract

Inflammation is a major underlying cause for obesity-associated metabolic diseases. Hence, anti-inflammatory dietary components may improve obesity-related disorders. We hypothesized that delta-tocotrienol (δT3), a member of the vitamin E family, reduces adiposity, insulin resistance and hepatic triglycerides through its anti-inflammatory properties. To test this hypothesis, C57BL/6J male mice were fed a high-fat diet (HF) with or without supplementation of δT3 (HF+δT3) at 400 mg/kg and 1600 mg/kg for 14 weeks, and they were compared to mice fed a low-fat diet (LF) or HF supplemented with metformin as an antidiabetic control. Glucose tolerance tests were administered 2 weeks prior to the end of treatments. Histology, quantitative polymerase chain reaction and protein analyses were performed to assess inflammation and fatty acid metabolism in adipose and liver tissues. Significant improvements in glucose tolerance, and reduced hepatic steatosis and serum triglycerides were observed in δT3-supplemented groups compared to the HF group. Body and fat pad weights were not significantly reduced in HF+δT3 groups; however, we observed smaller fat cell size and reduced macrophage infiltration in their adipose tissues compared to other groups. These changes were at least in part mechanistically explained by a reduction of mRNA and protein expression of proinflammatory adipokines and increased expression of anti-inflammatory adipokines in HF+δT3 mice. Moreover, δT3 dose-dependently increased markers of fatty acid oxidation and reduced markers of fatty acid synthesis in adipose tissue and liver. In conclusion, our studies suggest that δT3 may promote metabolically healthy obesity by reducing fat cell hypertrophy and decreasing inflammation in both liver and adipose tissue.

Yap WN

J Cosmet Dermatol. 2017 Sep 26. doi: 10.1111/jocd.12421.

Abstract

BACKGROUND:

UV radiation from the sun is the most common environmental stressor to damage the skin. It is now well established that photodamaged skin manifests signs of mild but chronic inflammation, termed as “inflammaging.” Thus, there is an urgent need for anti-inflammatory regimes that can limit the damage caused by inflammation.

OBJECTIVES:

This study aimed to evaluate the possible palliative effects of a new topical nanoemulsion formulation containing tocotrienol-rich fraction (TRF) on UV-induced inflammation (erythema) of human skin.

METHODS:

An in vitro model was used to demonstrate the ability of TRF to alleviate photodamage via attenuation of UV-induced oxidative stress and inflammation. Two ex vivo models (skin antioxidative potential and radical sun protection factor) were used to determine the efficacy of different formulations of TRF on the skin. A UV-induced erythema protection test in 20 subjects was conducted.

RESULTS:

In vitro studies involving HaCaT keratinocytes revealed that TRF possesses marked anti-inflammatory properties, as indicated by the attenuation of UV-induced upregulation of pro-inflammatory cytokines. A 1% TRF formulation was found to be more effective in enhancing the endogenous antioxidative protection of skin compared to 1% TRF in medium chain triglycerides because of its higher penetration kinetic profile. The clinical study showed that formulated TRF was effective in reducing skin redness after UV irradiation as early as after 6 hours of application. A significant depigmentation was also observed in TRF treatment subjects.

CONCLUSION:

TRF may serve as an anti-inflammatory compound that is safe to be applied daily to protect the skin from UV-induced inflammaging.