Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

Rattray NJW, Trivedi DK, Xu Y, Chandola T, Johnson CH, Marshall AD, Mekli K, Rattray Z, Tampubolon G, Vanhoutte B, White IR, Wu FCW, Pendleton N, Nazroo J, Goodacre R

Nat Commun. 2019 Nov 5;10(1):5027. doi: 10.1038/s41467-019-12716-2.

Abstract

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.

Trela A, Szymańska R

Food Chem. 2019 Oct 30;296:160-166. doi: 10.1016/j.foodchem.2019.05.185. Epub 2019 May 28.

Abstract

Vitamin E is a family of related compounds with different vitamin E activities and antioxidant properties that includes tocopherols, tocotrienols and plastochromanol-8. Plant oils could serve as an industrial source not only of tocopherols, but also tocotrienols and plastochromanol-8, which exhibit much stronger antioxidant activities than tocopherols. The aim of this study was a quantitative and qualitative analysis of vitamin E in certain plant oils. We demonstrated the presence of vitamin E derivatives in all the plant oils tested. The highest tocopherol contents were in pomegranate, wheat germ and raspberry seed oils. In general, γ-tocopherol was the predominant tocopherol homologue. Tocotrienols were also identified in most of the oils, but their content was much lower. The highest concentration of tocotrienols was in coriander seed oil. Plastochromanol-8 was present in most of the oils, but wheat germ oil was the richest source.

Arkoun B, Galas L, Dumont L, Rives A, Saulnier J, Delessard M, Rondanino C, Rives N

Int J Mol Sci. 2019 Oct 29;20(21). pii: E5380. doi: 10.3390/ijms20215380.

Abstract

Freezing-thawing procedures and in vitro culture conditions are considered as a source of stress associated with increased reactive oxygen species (ROS) generation, leading to a damaged cell aerobic metabolism and consequently to oxidative stress. In the present study, we sought to investigate whether vitamin E (Vit E) or reduced glutathione (GSH) enhances sperm production by decreasing ROS accumulation during in vitro maturation of prepubertal mice testes. Testes of prepubertal mice were cryopreserved using a freezing medium supplemented or not supplemented with Vit E and were cultured after thawing. In presence of Rol alone in culture medium, frozen-thawed (F-T) testicular tissues exhibited a higher ROS accumulation than fresh tissue during in vitro culture. However, Vit E supplementation in freezing, thawing, and culture media significantly decreased cytoplasmic ROS accumulation in F-T testicular tissue during in vitro maturation when compared with F-T testicular tissue cultured in the presence of Rol alone, whereas GSH supplementation in culture medium significantly increased ROS accumulation associated with cytolysis and tissue disintegration. Vit E but not GSH promoted a better in vitro sperm production and was a suitable ROS scavenger and effective molecule to improve the yield of in vitro spermatogenesis from F-T prepubertal mice testes. The prevention of oxidative stress in the cytoplasmic compartment should be regarded as a potential strategy for improving testicular tissue viability and functionality during the freeze-thaw procedure and in vitro maturation.

de Carvalho TS, Cardoso PB, Santos-Silva M, Lima-Bastos S, Luz WL, Assad N, Kauffmann N, Passos A, Brasil A, Bahia CP, Moraes S, Gouveia A Jr, de Jesus Oliveira Batista E, Oliveira KRMH, Herculano AM

Oxid Med Cell Longev. 2019 Oct 21;2019:8419810. doi: 10.1155/2019/8419810

Abstract

Anxiety is a common symptom associated with high caffeine intake. Although the neurochemical mechanisms of caffeine-induced anxiety remain unclear, there are some evidences suggesting participation of oxidative stress. Based on these evidences, the current study is aimed at evaluating the possible protective effect of alpha-tocopherol (TPH) against anxiety-like behavior induced by caffeine (CAF) in zebrafish. Adult animals were treated with CAF (100 mg/kg) or TPH (1 mg/kg)+CAF before behavioral and biochemical evaluations. Oxidative stress in the zebrafish brain was evaluated by a lipid peroxidation assay, and anxiety-like behavior was monitored using light/dark preference and novel tank diving test. Caffeine treatment evoked significant elevation of brain MDA levels in the zebrafish brain, and TPH treatment prevented this increase. Caffeine treatment also induced anxiety-like behavior, while this effect was not observed in the TPH+CAF group. Taken together, the current study suggests that TPH treatment is able to inhibit oxidative stress and anxiety-like behavior evoked by caffeine.

Di Vincenzo A, Tana C, El Hadi H, Pagano C, Vettor R, Rossato M

nt J Mol Sci. 2019 Oct 15;20(20). pii: E5101. doi: 10.3390/ijms20205101.

Abstract

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.

El-Hak HNG, ELaraby EE, Hassan AK, Abbas OA

Heliyon. 2019 Oct 12;5(10):e02645. doi: 10.1016/j.heliyon.2019.e02645

Abstract

The aim of these investigations was to study vitamin E supplement effect in male albino rats after 30 days of repeated treatment. Four groups of six male rats were orally administered distilled water (control), 500, 1000 and 2000 mg/kg body weight vitamin E daily for 30 days. The impact of the treatment on percent body weight and mortality was determined and compared to the control group. Some hematological analysis, biochemical parameters and histological examination of different body organs were assessed. The rats treated with different doses of vitamin E supplement showed no deaths recorded in 30 days. The treatment with higher dose Vitamin E supplementation” caused significant alteration at the hematological, biochemical and histological level. Therefore, oral administration of vitamin E supplement in rats for 30 days was not safe for the liver and kidney and in the other hand, safe for the testes therefore that side effect on the liver and kidney should be considered when recommended vitamin E for therapeutic purpose. Care should be taken in taking high doses of vitamin E.

Testa D, Marcuccio G, Lombardo N, Cocuzza SG, Guerra G, Motta G

Ear Nose Throat J. 2019 Oct 2:145561319870483. doi: 10.1177/0145561319870483.

Abstract

Primary atrophic rhinitis is a disease of the nose and of paranasalsinuses characterized by a progressive loss of function of nasal and paranasal mucosa caused by a gradual destruction of ciliary mucosalepithelium with atrophy of serous-mucous glands and loss of bonestructures.The aim of this study was to evaluate the therapeutic effects of topic α-tochopherol acetate (vitamin E) in patients with primary atrophicrhinitis based on subjective and objective data.We analyzed 44 patients with dry nose sensation and endoscopic evidence of atrophic nasal mucosa. We analyzed endoscopic mucosascore, anterior rhinomanometry, and nasal mucociliary clearance before and after 6 months of topic treatment with α-tochopherol acetate. For statistical analysis, we used paired samples t test (95% confidence interval [CI], P < .05) for rhinomanometric and muciliary transit time evaluations and analysis of variance 1-way test (95% CI, P < .05) for endoscopic evaluation. All patients showed an improvement in “dry nose” sensation and inperception of nasal airflow. Rhinomanometric examination showed increase of nasal airflow at follow-up (P < .05); nasal mucociliaryclearance showed a reduction in mean transit time (P < .05); and endoscopic evaluation showed significative improvement of hydration of nasalmucosa and significative decreasing nasal crusts and mucusaccumulation (P < .05). Medical treatment for primary atrophic rhinitis is not clearly documented in the literature; in this research, it was demonstrated that α-ochopherol acetate could be a possible treatment for atrophic rhinitis.

Wallert M, Ziegler M, Wang X, Maluenda A, Xu X, Yap ML, Witt R, Giles C, Kluge S, Hortmann M, Zhang J, Meikle P, Lorkowski S, Peter K

Redox Biol. 2019 Sep;26:101292. doi: 10.1016/j.redox.2019.101292.

Abstract

OBJECTIVE:

Myocardial infarction (MI) is a leading cause of mortality and morbidity worldwide and new treatment strategies are highly sought-after. Paradoxically, reperfusion of the ischemic myocardium, as achieved with early percutaneous intervention, results in substantial damage to the heart (ischemia/reperfusion injury) caused by cell death due to aggravated inflammatory and oxidative stress responses. Chronic therapy with vitamin E is not effective in reducing the cardiovascular event rate, presumably through failing to reduce atherosclerotic plaque instability. Notably, acute treatment with vitamin E in patients suffering a MI has not been systematically investigated.

METHODS AND RESULTS:

We applied alpha-tocopherol (α-TOH), the strongest anti-oxidant form of vitamin E, in murine cardiac ischemia/reperfusion injury induced by ligation of the left anterior descending coronary artery for 60 min. α-TOH significantly reduced infarct size, restored cardiac function as measured by ejection fraction, fractional shortening, cardiac output, and stroke volume, and prevented pathological changes as assessed by state-of-the-art strain and strain-rate analysis. Cardioprotective mechanisms identified, include a decreased infiltration of neutrophils into cardiac tissue and a systemic anti-inflammatory shift from Ly6C^high to Ly6C^low monocytes. Furthermore, we found a reduction in myeloperoxidase expression and activity, as well as a decrease in reactive oxygen species and the lipid peroxidation markers phosphatidylcholine (PC) (16:0)-9-hydroxyoctadecadienoic acid (HODE) and PC(16:0)-13-HODE) within the infarcted tissue.

CONCLUSION:

Overall, α-TOH inhibits ischemia/reperfusion injury-induced oxidative and inflammatory responses, and ultimately preserves cardiac function. Therefore, our study provides a strong incentive to test vitamin E as an acute therapy in patients suffering a MI.

Liu KY, Jiang Q

J Nutr. 2019 Sep 9. pii: nxz217. doi: 10.1093/jn/nxz217.

Abstract

BACKGROUND:

Vitamin E α-, γ-, or δ-tocopherol (αT, γT, δT) and γ- or δ-tocotrienol (γTE, δTE) are metabolized to hydroxychromanols and carboxychromanols including 13′-carboxychromanol (13′-COOH), 11′-COOH, and carboxyethyl hydroxychroman (CEHC), some of which have unique bioactivities compared with the vitamers. However, the bioavailability of these metabolites has not been well characterized.

OBJECTIVE:

We investigated the pharmacokinetics (PK) of vitamin E forms and metabolites in rats.

METHODS:

Six-week-old male Wistar rats received 1-time gavage of γT-rich tocopherols (50 mg/kg) containing γT/δT/αT (57.7%, 21.9%, and 10.9%, respectively) or δTE-rich tocotrienols (35 mg/kg) containing δTE/γTE (8:1). We quantified the time course of vitamin E forms and metabolites in the plasma and their 24-h excretion to the urine and feces. The general linear model repeated measure was used for analyses of the PK data.

RESULTS:

In the rats’ plasma, Cmax of γT or δTE was 25.6 ± 9.1 μM (Tmax = 4 h) or 16.0 ± 2.3 μM (Tmax = 2 h), respectively, and sulfated CEHCs and sulfated 11′-COOHs were the predominant metabolites with Cmax of 0.4-0.5 μM (Tmax ∼5-7 h) or ∼0.3 μM (Tmax at 4.7 h), respectively. In 24-h urine, 2.7% of γT and 0.7% of δTE were excreted as conjugated CEHCs. In the feces, 17-45% of supplemented vitamers were excreted as unmetabolized forms and 4.9-9.2% as unconjugated carboxychromanols, among which 13′-COOHs constituted ∼50% of total metabolites and the amount of δTE-derived 13′-COOHs was double that of 13′-COOH derived from γT.

CONCLUSIONS:

PK data of vitamin E forms in rats reveal that γT, δT, γTE, and δTE are bioavailable in the plasma and are mainly excreted as unmetabolized forms and long-chain metabolites including 13′-COOHs in feces, with more metabolites from tocotrienols than from tocopherols.

Cui H, Huang J, Lu M, Zhang Q, Qin W, Zhao Y, Lu X, Zhang J, Xi Z, Li R

Environ Pollut. 2019 Sep;252(Pt B):1519-1531. doi: 10.1016/j.envpol.2019.06.092. Epub 2019 Jun 26.

Abstract

Some basic research has shown that nanomaterials can aggravate allergic asthma. However, its potential mechanism is insufficient. Based on the research that alumina nanopowder (nAl₂O₃) has been reported to cause lung tissue damage, the purpose of this study was to explore the relationship between nAl₂O₃ and allergic asthma as well as its molecular mechanism. In this study, Balb/c mice were sensitized with ovalbumin (OVA) to construct the allergic asthma model while intratracheally administered 0.5, 5 or 50 mg kg^-1·day^-1 nAl₂O₃ for 3 weeks. It was observed that exposure to nAl₂O₃ exacerbated airway hyperresponsiveness (AHR), airway remodeling, and inflammation cell infiltration, leading to lung function damage in mice. Results revealed that nAl₂O₃ could increase ROS levels and decrease GSH levels in lung tissue, promote the increases of the T-IgE, TGF-β, IL-1β and IL-6 levels, stimulate the overexpression of transcription factors GATA-3 and RORγt, decrease the levels of IFN-γ and IL-10 and increase the levels of IL-4 and IL-17A, resulting in the imbalance of Th1/Th2 and Treg/Th17 immune responses. In addition, antioxidant Vitamin E (Vit E) could alleviate asthma-like symptoms through blocking oxidative stress. The study displayed that exposure of nAl₂O₃ deteriorated allergic asthma through promoting the imbalances of Th1/Th2 and Treg/Th17.