Serum vitamin E as a significant prognostic factor in patients with dyslipidemia disorders

Barzegar-Amini M, Ghazizadeh H, Seyedi SMR, Sadeghnia HR, Mohammadi A, Hassanzade-Daloee M, Barati E, Kharazmi-Khorassani S, Kharazmi-Khorassani J, Mohammadi-Bajgiran M, Tavallaie S, Ferns GA, Mouhebati M, Ebrahimi M, Tayefi M, Ghayour-Mobarhan M

Diabetes Metab Syndr. 2019 Jan - Feb;13(1):666-671. doi: 10.1016/j.dsx.2018.11.034. Epub 2018 Nov 13.

Abstract

OBJECTIVES:

Obesity and overweight are among the main causes of cardiovascular disease (CVD) mortality. Dyslipidemia, fatty liver index, is strongly related to CVD. Vitamin E as an antioxidant protects the hepatic cells against oxidative stress and prevents fatty liver disease. The aim of the current study is to evaluate the relationship between anthropometric parameters and fasted lipid profile with serum vitamin Elevels.

STUDY DESIGN:

A randomized trial was designed based on data from the Mashhad stroke and heart atherosclerotic disorders (MASHAD: 2010-2020).

METHODS:

363 CVD subjects (173 males and 190 females) was selected at random, among 9704 subjects in three regions of Mashhad, northeast of Iran to investigate the specific correlations among their serum vitamin E, lipid profile (TG, HDL-C, LDL-C and TC), and anthropometric features (height, weight, BMI, hip and waist circumferences.

RESULT:

The results indicated the significant relationships between vitamin E, and fasting serum lipid profile in subjects. Serum vitamin Ewas negatively correlated to TC, TG, and LDL-C and positively related to HDL-C. Also, statistically negative correlations were found between vitamin E and anthropometric parameters (weight, waist and hip circumference, middle Arm, and Systolic Blood Pressure). Moreover, vitamin E ratios such as vitamin E/(TC + TG) and vitamin E/TC values as standardized vitamin E, had significant negative correlation with BMI, the whole of anthropometric parameters, and dyslipidemia risk factors including TC, TG and LDL-C.

CONCLUSION:

We found that vitamin E profile was significantly lower in the dyslipidemia subjects. It is generally suggested that vitamin E monitoring might be used as a useful prognostic and therapeutic agent in dyslipidemia disorder.

Yan B, Sun Y, Zeng J, Chen Y, Li C, Song P, Zhang L, Yang X, Wu Y, Ma P

Toxicol Appl Pharmacol. 2019 Feb 15;368:1-17. doi: 10.1016/j.taap.2019.02.008. [Epub ahead of print]

Abstract

Learning disabilities (LDs) in children are a serious global problem. Dibutyl phthalate (DBP), a plasticizer widely used in daily life, has been linked to triggering childhood LDs, however the mechanism underlying this remains unclear. Studies have shown that the ERK 1/2 pathway is closely related to apoptosis of hippocampal neurons. On the basis of these links between LDs, DBP and the ERK 1/2 pathway, we explore whether DBP induces hippocampal neuron apoptosis and increases behavioral disorders in mice via the ERK 1/2 pathway. We looked at oxidative stress, examined the calcium signal, detected the ERK 1/2 pathway and evaluated apoptosis as well as using histological observations, and found that DBP significantly increased oxidative damage and apoptosis in hippocampal neurons via the ERK 1/2 pathway in mice. We also found that pretreatment with the dihydropyridine’s (DHP’s) Ca²⁺ antagonist, nimodipine (NMDP), combined with the antioxidant Vitamin E (VE), attenuated ERK 1/2 phosphorylation and DBP-mediated disorders, suggesting that a combined use of VE and NMDP can ameliorate DBP-induced memory deficit and apoptosis via inhibiting the ERK 1/2 pathway. These results indicate that DBP predisposes oxidative damage and apoptosis in hippocampal neurons by activation of the ERK 1/2 pathway, and may be proposed as a possible mechanism underlying LDs in children. Moreover, VE and NMDP may play a certain protective role in the targeted treatment of childhood LDs.

Nobili V, Alisi A, Mosca A, Crudele A, Zaffina S, Denaro M, Smeriglio A, Trombetta D

Antioxid Redox Signal. 2019 Feb 11. doi: 10.1089/ars.2018.7704. [Epub ahead of print]

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for pediatric nonalcoholic steatohepatitis. We performed a randomized, double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD. Four hundred forty consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo for 4 months. Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin resistance (IR), triglyceride levels, oxidative stress parameters, and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins. The HXT and vitamin Etreatment improved the main oxidative stress parameters, IR, and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD-related liver damage in children.

Mahdi H, Tahereh H, Esmaiel S, Massood E

Toxicol Ind Health. 2019 Feb;35(2):136-144. doi: 10.1177/0748233718818692. Epub 2019 Jan 16.

Abstract

The aim of this study was to evaluate the role of apoptosis in the first-generation pups’ testicular and ovarian tissue changes following mancozeb (MNZ) administration during intrauterine and lactating periods and also the preventive effect of the co-administration of vitamins E and C on these changes. Naval Medical Research Institute (NMRI) pregnant mice were randomly divided into six groups: control, vehicle, MNZ, vitamin E plus MNZ, vitamin C plus MNZ and vitamins E and C plus MNZ. Administered doses of MNZ and vitamins E and C were 500, 200 and 100 mg/kg of body weight, respectively. These agents were administered to the animals by oral gavage every 2 days. Vitamin treatment was carried out 30 min prior to MNZ administration. Treatment was started on the second day of gestation and continued until weaning. Separated testes and ovaries of animals were prepared for apoptosis detection by terminal deoxynucleotidyl transferase end-labeling (TUNEL) staining. The percentage of TUNEL-positive cells was reported using the 4,6-diamidino-2-phenylindole method. As compared to the control and vehicle groups, MNZ induced a significant increase ( p < 0.001) in the number of TUNEL-positive cells. The administration of both vitamins E and C alone and together significantly ( p < 0.001) prevented the apoptotic impacts of MNZ. The preventive effect of the co-administration of these vitamins on the ovary was greater compared to the single administration of vitamins E ( p < 0.001) or C ( p < 0.001). Meanwhile, the results revealed the stronger preventive effect of vitamin C as compared to E on testicular tissue ( p < 0.05). The apoptotic impact of MNZ exposure during intrauterine and lactating periods on first-generation testicular and ovarian tissues was significant. The co-administration of vitamins E and C could prevent MNZ-induced testicular and ovarian changes.

Fontana F, Moretti RM, Raimondi M, Marzagalli M, Beretta G, Procacci P, Sartori P, Montagnani Marelli M, Limonta P

Cell Prolif. 2019 Feb 4:e12576. doi: 10.1111/cpr.12576. [Epub ahead of print]

Abstract

OBJECTIVES:

Prostate cancer, after the phase of androgen dependence, may progress to the castration-resistant prostate cancer (CRPC) stage, with resistance to standard therapies. Vitamin E-derived tocotrienols (TTs) possess a significant antitumour activity. Here, we evaluated the anti-cancer properties of δ-TT in CRPC cells (PC3 and DU145) and the related mechanisms of action.

MATERIALS AND METHODS:

MTT, Trypan blue and colony formation assays were used to assess cell viability/cell death/cytotoxicity. Western blot, immunofluorescence and MTT analyses were utilized to investigate apoptosis, ER stress and autophagy. Morphological changes were investigated by light and transmission electron microscopy.

RESULTS:

We demonstrated that δ-TT exerts a cytotoxic/proapoptotic activity in CRPC cells. We found that in PC3 cells: (a) δ-TT triggers both the endoplasmic reticulum (ER) stress and autophagy pathways; (b) autophagy induction is related to the ER stress, and this ER stress/autophagy axis is involved in the antitumour activity of δ-TT; in autophagy-defective DU145 cells, only the ER stress pathway is involved in the proapoptotic effects of δ-TT; (c) in both CRPC cell lines, δ-TT also induces an intense vacuolation prevented by the ER stress inhibitor salubrinal and the protein synthesis inhibitor cycloheximide, together with increased levels of phosphorylated JNK and p38, supporting the induction of paraptosis by δ-TT.

CONCLUSIONS:

These data demonstrate that apoptosis, involving ER stress and autophagy (in autophagy positive PC3 cells), and paraptosis are involved in the anti-cancer activity of δ-TT in CRPC cells.

Aggarwal V, Kashyap D, Sak K, Tuli HS, Jain A, Chaudhary A, Garg VK, Sethi G, Yerer MB

Int J Mol Sci. 2019 Feb 2;20(3). pii: E656. doi: 10.3390/ijms20030656.

Abstract

Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed.

de Souza CP, Gambeta E, Stern CAJ, Zanoveli JM

Behav Brain Res. 2019 Feb 1;359:749-754. doi: 10.1016/j.bbr.2018.09.008. Epub 2018 Sep 13

Abstract

Anxiety and stress disorders, such as posttraumatic stress disorder (PTSD) have been described as debilitating comorbidities of diabetes. In the present study, we aimed to investigate anxiety-like behavior and the extinction and generalization of aversive memories in fear conditioning using a streptozotocin-induced model of diabetes (DBT). Moreover, considering that DBT animals present increased oxidative stress in brain areas related to anxiety and memory, we aimed to evaluate the effect of prolonged treatment with antioxidant vitamin E on behavioral parameters of anxiety and fear memory and on the diabetic condition. It was observed that DBT animals showed a deficiency in extinguishing the aversive memory in a fear conditioning test, along with a generalization of the fear memory. They also present a more pronounced anxiety-like behavior in the elevated plus maze test. VIT E treatment (300 mg/kg, p.o.) was not able to reduce hyperglycemia; however, it was able to block the anxiogenic-like behavior, also improving the deficit in the extinction of the aversive memory as well as blocking the generalization of such memory in a different context. Taken together, our data suggest that DBT animals are prone to extinction deficits and generalization of fear memories, behaviors which are observed in models of PTSD. Lastly, prolonged VIT E supplementation may be effective in the treatment of anxiety, extinction deficit and generalization of fear memories induced by the diabetic condition.

Zarkasi KA, Jen-Kit T, Jubri Z

Trop Anim Health Prod. 2019 Jan 31. doi: 10.1007/s11250-019-01826-0. [Epub ahead of print]

Abstract

Myocardial infarction is a major cause of deaths globally. Modulation of several molecular mechanisms occur during the initial stages of myocardial ischemia prior to permanent cardiac tissue damage, which involve both pathogenic as well as survival pathways in the cardiomyocyte. Currently, there are increasing evidence regarding the cardioprotective role of vitamin E in alleviating the disease. This fat-soluble vitamin does not only act as a powerful antioxidant; it also has the ability to regulate several intracellular signalling pathways including HIF-1, PPAR-γ, Nrf-2, and NF-κB that influence the expression of a number of genes and their protein products. Essentially, it inhibits the molecular progression of tissue damage and preserves myocardial tissue viability. This review aims to summarize the molecular understanding of the cardiomodulation in myocardial infarction as well as the mechanism of vitamin E protection.

Wang J, Guo H, Lin T, Song Y, Zhang H, Wang B, Zhang Y, Li J, Huo Y, Wang X, Qin X, Xu X.

J Acad Nutr Diet. 2019 Jan 31. pii: S2212-2672(18)30852-9. doi: 10.1016/j.jand.2018.11.017. [Epub ahead of print]

Abstract

BACKGROUND:

Evidence from epidemiologic studies has been inconsistent regarding the role of vitamin E in cancer incidence risk.

OBJECTIVE:

The aim of this study was to evaluate the prospective association between baseline plasma vitamin E levels and subsequent cancer risk in Chinese adults with hypertension, and to identify effect modifiers.

DESIGN:

A nested, case-control study was conducted from 20,702 hypertensive participants in the China Stroke Primary Prevention Trial, a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013.

PARTICIPANTS:

The current study included 229 new cancer cases and 229 controls matched for age (±1 year), sex, treatment group, and study site.

MAIN OUTCOME MEASURES:

Plasma vitamin E was measured by liquid chromatography with tandem quadrupole mass spectrometers and plasma selenium was measured by inductively coupled plasma mass spectrometry using Thermo Fisher iCAP Q ICP-MS.

STATISTICAL ANALYSES:

Odds ratios (OR) of cancer in relation to plasma concentrations of vitamin E were calculated using conditional logistic regression models.

RESULTS:

Median follow-up duration was 4.5 years. Overall, vitamin E was not associated with subsequent risk of total cancer (per 1-mg/L [2.3 μmol/L] increase: OR 1.01, 95% CI 0.93 to 1.09) and non-gastrointestinal cancer (OR 1.10, 95% CI 0.98 to 1.24). However, there was a significant, inverse association between vitamin E and gastrointestinal cancer (OR 0.86, 95% CI 0.75 to 0.99), particularly esophageal cancer (OR 0.67, 95% CI 0.48 to 0.95). Moreover, high vitamin E decreased the risk of total cancer (OR 0.91, 95% CI 0.84 to 0.99) and gastrointestinal cancer (OR 0.83, 95% CI 0.73 to 0.95) among patients with high selenium levels (median≥83.7 μg/L [1.1 μmol/L]), and increased the risk of total cancer (OR 1.13, 95% CI 1.00 to 1.26) and non-gastrointestinal cancer (OR 1.25, 95% CI 1.03 to 1.50) among those with low selenium levels (<83.7 μg/L [1.1 μmol/L]).

CONCLUSIONS:

This study suggests that higher levels of plasma vitamin E are associated with reduced risk of gastrointestinal cancer. High vitamin E decreased the risk of total cancer among patients with high selenium levels, but increased the risk of total cancer among those with low selenium levels.

Hussain MI, Ahmed W, Nasir M, Mushtaq MH, Sheikh AA, Shaheen AY, Mahmood A

Pak J Pharm Sci. 2019 Jan;32(1(Supplementary)):269-276.

Abstract

Tuberculosis is one of the leading causes of mortality in Pakistan which is linked with malnutrition and weak immunity. Such people are more prone to chronic infections including TB. The current study aimed to assess the effect of supplementation of Vitamin E on the immune status of human subjects against pulmonary tuberculosis. A total of 80 patients with pulmonary TB were divided into treatment group (vitamin E) and control group (Anti-tuberculosis regime). Presence of acid fast bacilli in sputum sample, Erythrocyte sedimentation rate, total leucocytes counts, body mass index and mid arm muscle circumference (MAMC) were recorded as per standard protocol. Levels of vitamin E, IgG, IgM and T-Cell count were determined before and after treatment. The results showed that 16% males and 33% females were underweight who consumed 1145 kcal energy instead of 2270 kcal per day and 19.5 gram protein instead of 78.6 grams. A non significant effect of vitamin Eon ESR and TLC values was observed but significant increase in level of immunoglobulins (IgG, IgM) and T-cell types (CD4+ and CD8+) was observed in patients as compared to control group. Results indicate that vitamin E plays important role in enhancing immunity of patients against TB.