Vitamins D and E Stimulate the PI3K-AKT Signalling Pathway in Insulin-Resistant SK-N-SH Neuronal Cells

Zaulkffali AS, Md Razip NN, Syed Alwi SS, Abd Jalil A, Abd Mutalib MS, Gopalsamy B, Chang SK, Zainal Z, Ibrahim NN, Zakaria ZA, Khaza'ai H

Nutrients. 2019 Oct 19;11(10). pii: E2525. doi: 10.3390/nu11102525.

Abstract

This study investigated the effects of vitamins D and E on an insulin-resistant model and hypothesized that this treatment would reverse the effects of Alzheimer’s disease (AD) and improves insulin signalling. An insulin-resistant model was induced in SK-N-SH neuronal cells with a treatment of 250 nM insulin and re-challenged with 100 nM at two different incubation time (16 h and 24 h). The effects of vitamin D (10 and 20 ng/mL), vitamin E in the form of tocotrienol-rich fraction (TRF) (200 ng/mL) and the combination of vitamins D and E on insulin signalling markers (IR, PI3K, GLUT3, GLUT4, and p-AKT), glucose uptake and AD markers (GSK3β and TAU) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The results demonstrated an improvement of the insulin signalling pathway upon treatment with vitamin D alone, with significant increases in IR, PI3K, GLUT3, GLUT4 expression levels, as well as AKT phosphorylation and glucose uptake, while GSK3β and TAU expression levels was decreased significantly. On the contrary, vitamin E alone, increased p–AKT, reduced the ROS as well as GSK3β and TAU but had no effect on the insulin signalling expression levels. The combination of vitamins D and E only showed significant increase in GLUT4, p-AKT, reduced ROS as well as GSK3β and TAU. Thus, the universal role of vitamin D, E alone and in combinations could be the potential nutritional agents in restoring the sensitivity of neuronal cells towards insulin and delaying the pathophysiological progression of AD.

Sebastiani G, Saeed S, Lebouche B, de Pokomandy A, Szabo J, Haraoui LP, Routy JP, Wong P, Deschenes M, Ghali P, Klein M; LIVEHIV Study Group.

AIDS. 2019 Oct 16. doi: 10.1097/QAD.0000000000002412.

Abstract

OBJECTIVE:

Human immunodeficiency virus (HIV)-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown.

DESIGN:

Single centre, phase IV, open-label, single arm clinical trial.

METHODS:

HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) ≥ 248 dB/m, and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) >130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks post-discontinuation. Generalized linear mixed effects models were used to evaluate changes in ALT, CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pre-treatment trends.

RESULTS:

A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared to baseline, 24 weeks of vitamin E treatment improved ALT (-27 units/L; 95% confidence interval [CI] -37, –17), CAP scores (-22 dB/m; 95% CI -42, -1) and CK-18 (-123 units/L; 95% CI -201, -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up.

CONCLUSION:

In this first clinical trial, we showed that vitamin E is an effective and well-tolerated treatment for NASH in HIV-infected patients.

Eid RA, Al-Shraim M, Zaki MS, Kamar SS, Abdel Latif NS, Negm S, Al-Ani B, Haidara MA

Ultrastruct Pathol. 2019;43(4-5):199-208. doi: 10.1080/01913123.2019.1673860.

Abstract

Food additives such as nitrates and nitrites, and monosodium glutamate (MSG) used in the food industry increase the risk of certain cancers and inflict damage to vital organs. We sought to determine whether the antioxidant vitamin E can protect against liver injuries induced by a toxic dose of MSG in a rat model of MSG-induced acute liver injury. The model group of rats received a daily dose of MSG (4 gm/kg) for 7 days, whereas the protective groups were either received a 100 mg/kg vitamin E plus MSG or 300 mg/kg vitamin E plus MSG for 7 days. Rats were then sacrificed at day 8. Transmission and light microscopy images revealed substantial liver tissue damage induced by MSG in the model group as demonstrated by apoptotic hepatocytes with Pyknotic nuclei and irregular nuclear membrane, and cytoplasm displayed many vacuoles, swollen mitochondria, dilated endoplasmic reticulum, dilated blood sinusoids and bundles of collagen fibers in extracellular space. Treatment of the model group with vitamin E showed a substantial protection of liver tissue and hepatocellular architecture by 300 mg/kg vitamin E compared to a partial protection by 100 mg/kg vitamin E. In addition, MSG significantly (p < .05) modulated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly (p < .05) protected with vitamin E. Thus, vitamin E at 300 mg/kg effectively protects against MSG-induced acute liver injury in rats, possibly via the inhibition of inflammation, and up-regulation of endogenous antioxidants.

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.

Odai T, Terauchi M, Hirose A, Kato K, Miyasaka N

Nutrients. 2019 Oct 15;11(10). pii: E2474. doi: 10.3390/nu11102474.

Abstract

This study aimed to investigate the relationship between the consumption of various nutrients and bone mineral density (BMD) in middle-aged women. This cross-sectional survey was conducted based on the clinical records of 157 women aged 38-76. Their lumbar spine BMD was measured with dual-energy X-ray absorptiometry and dietary habits were assessed with the brief-type self-administered diet history questionnaire. Participants were divided into premenopausal (n = 46) and postmenopausal (n = 111) groups and the correlation between the BMD Z-score (Z-score) and the intakes of 43 nutrients was investigated separately for each group. In premenopausal women, the daily intake of ash, calcium, and α-tocopherol was positively correlated with the Z-score (Pearson’s correlation coefficient, R = 0.31, 0.34, 0.33, p = 0.037, 0.020, 0.027, respectively). When dividing the consumption of ash, calcium, and α-tocopherol into low, middle, and high tertiles, the Z-score significantly differed only between the α-tocopherol tertiles. After adjustment for age, body mass index, and lifestyle factors, daily intake of α-tocopherol remained significantly associated with the Z-score (regression coefficient = 0.452, p = 0.022). No nutrient was found to be significantly correlated with the Z-score in postmenopausal women. Increase in the intake of α-tocopherol could help maintain bone mass in premenopausal women.

Rajagopalan P, Jain AP, Nanjappa V, Patel K, Mangalaparthi KK, Babu N, Cavusoglu N, Roy N, Soeur J, Breton L, Pandey A, Gowda H, Chatterjee A, Misra N

J Dermatol Sci. 2019 Oct 15. pii: S0923-1811(19)30273-7. doi: 10.1016/j.jdermsci.2019.08.009.

Abstract

BACKGROUND:

Skin acts as a protective barrier against direct contact with pollutants but inhalation and systemic exposure have indirect effect on keratinocytes. Exposure to diesel exhaust has been linked to increased oxidative stress.

OBJECTIVE:

To investigate global proteomic alterations in diesel particulate extract (DPE)/ its vapor exposed skin keratinocytes.

METHODS:

We employed Tandem Mass Tag (TMT)-based proteomics to study effect of DPE/ DPE vapor on primary skin keratinocytes.

RESULTS:

We observed an increased expression of oxidative stress response protein NRF2, upon chronic exposure of primary keratinocytes to DPE/ its vapor which includes volatile components such as polycyclic aromatic hydrocarbons (PAHs). Mass spectrometry-based quantitative proteomics led to identification 4490 proteins of which 201 and 374 proteins were significantly dysregulated (≥1.5 fold, p ≤ 0.05) in each condition, respectively. Proteins involved in cellular processes such as cornification (cornifin A), wound healing (antileukoproteinase) and differentiation (suprabasin) were significantly downregulated in primary keratinocytes exposed to DPE/ DPE vapor. These results were corroborated in 3D skin models chronically exposed to DPE/ DPE vapor. Bioinformatics analyses indicate that DPE and its vapor affect distinct molecular processes in skin keratinocytes. Components of mitochondrial oxidative phosphorylation machinery were seen to be exclusively overexpressed upon chronic DPE vapor exposure. In addition, treatment with an antioxidant like vitamin E partially restores expression of proteins altered upon exposure to DPE/ DPE vapor.

CONCLUSIONS:

Our study highlights distinct adverse effects of chronic exposure to DPE/ DPE vapor on skin keratinocytes and the potential role of vitamin E in alleviating adverse effects of environmental pollution.

Mahdinia R, Goudarzi I, Lashkarbolouki T, Salmani ME

Nutr Neurosci. 2019 Oct 14:1-15. doi: 10.1080/1028415X.2019.1674523.

Abstract

Objective: Alcohol exposure during pregnancy affects the developing fetus and causes a variety of physical and neurological abnormalities. Here we aim to study the effects of vitamin E on spatial learning and memory deficits and on changes in hippocampal brain-derived neurotrophic factor (BDNF) levels following perinatal ethanol exposure in rats. Method: Pregnant Wistar rats received ethanol (4 g/kg) and vitamin E (doses of 100, 200, and 400 mg/kg) on day 0 of gestation (GD) until weaning (28 days). On postnatal days (PND) 29, the performance of spatial learning and memory of rats were measured using the Morris water maze (MWM). The expression of BDNF protein levels in the hippocampus was assayed using BDNF ELISA kits. Results: Ethanol exposed group showed higher escape latency during training, reduced time spent in the target quadrant, higher escape location latency and average proximity in probe test. Vitamin E with doses of 100, 200 and 400 mg/kg significantly reduced escape latency during training. Also, vitamin E (400 mg/kg) significantly increased time spent in target quadrant, decreased escape location latency and average proximity in probe test. Maternal ethanol treatment significantly reduced the expression of BDNF protein in the hippocampus of offspring, whereas administration of vitamin E (400 mg/kg) significantly increased hippocampal BDNF in ethanol-treated rats. Discussion: Vitamin E administration dose-dependently ameliorate learning and memory deficits induced by perinatal ethanol exposure and increased hippocampal BDNF levels. BDNF may be implicated in the beneficial effects of vitamin E on learning and memory in the perinatal ethanol-exposed rat.

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.