Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease

Ivancovsky-Wajcman D, Fliss-Isakov N, Salomone F, Webb M, Shibolet O, Kariv R, Zelber-Sagi S

Dig Liver Dis. 2019 Jul 4. pii: S1590-8658(19)30662-0. doi: 10.1016/j.dld.2019.06.005. [Epub ahead of print]

Abstract

BACKGROUND & AIMS:

Although antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers.

METHODS:

Cross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1-F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ).

RESULTS:

Overall, 789 subjects were included (52.6% men, age 58.83 ± 6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43-0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30-0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47-0.99, P = 0.045; OR = 0.57, 0.38-0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest.

CONCLUSION:

Vitamin E and C intake may be protective from NAFLD-related liver damage.

Alzoubi KH, Hasan ZA, Khabour OF, Mayyas FA, Al Yacoub ON, Banihani SA, Alomari MA, Alrabadi NN

Physiol Behav. 2019 Jul 1;206:200-205. doi: 10.1016/j.physbeh.2019.04.011. Epub 2019 Apr 13.

Abstract

There is increasing evidence that oxidative stress is a causal factor in different neurodegenerative disorders such as Alzheimer’s disease and epilepsy. High-fat diet (HFD) has been shown to induce oxidative stress and neuronal damage that may increase susceptibility to seizures. The present study was undertaken to investigate the relationships between vitamin E, a potent antioxidant, HFD, and chemically induced seizures, using the PTZ seizure model in rats. Animals were randomly assigned into four groups: control, HFD, vitamin E (Vit E), and high-fat diet with vitamin E (HFD + Vit E) group. Vitamin E and/or HFD were administered to animals for 6 weeks. Thereafter, PTZ seizure threshold was measured in control and treated rats, and different brain regions were analyzed for levels of oxidative stress biomarkers. Current results revealed a significant reduction in PTZ seizure threshold in rats consuming HFD, which could be prevented by vitamin E supplement. Alongside, vitamin E supplement prevented HFD induced changes in oxidative stress biomarkers and capacity enzymes. Therefore, current results suggest that prolonged consumption of HFD increases susceptibility to PTZ induced seizures, which may be related to HFD induced oxidative stress. This increase in the PTZ susceptibility could be prevented by the administration of vitamin E, probably through its antioxidant effect, particularly at the brain hippocampal region.

Rahimi Anbarkeh F, Nikravesh MR, Jalali M, Sadeghnia HR, Sargazi Z

Int J Fertil Steril. 2019 Jul;13(2):154-160. doi: 10.22074/ijfs.2019.5612. Epub 2019 Apr 27.

Abstract

BACKGROUND:

Diazinon (DZN) is an organophosphate pesticide, and nowadays this pesticide is mostly used in agriculture. In this study, we analyzed the effects of DZN and vitamin E (Vit E) on apoptosis and the proliferation of germ cells in rat testis.

MATERIALS AND METHODS:

In this experimental study, 30 male Wistar rats were divided into five groups (n=6 per group) consisting of control, sham (received olive oil), experimental group i (60 mg/kg DZN), experimental group ii (60 mg/kg DZN and 200 mg/kg Vit E), and experimental group iii (200 mg/kg Vit E). After six weeks, left testis of rats was removed for the detection of proliferative cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase end-labeling (TUNEL).

RESULTS:

Compared with the control group, DZN in the experimental group i decreased the number of PCNA-positive cells and increased the number of TUNEL-positive cells (P<0.001). Vit E improved detrimental changes by the decrease in the rate of apoptosis and the increase in the proliferation of testicular germ cells (P<0.001).

CONCLUSION:

Vit E can decrease the number of TUNEL-positive cells and increase the number of PCNA-positive cells by the neutralization of the toxicity caused by DZN in the testicular tissue.

Vaz S, Silva R, Amaral MH, Martins E, Sousa Lobo JM, Silva AC

Colloids Surf B Biointerfaces. 2019 Jul 1;179:242-249. doi: 10.1016/j.colsurfb.2019.03.036. Epub 2019 Apr 3.

Abstract

Lipid-based nanosystems, such as nanostructured lipid carriers (NLC) and nanoemulsions (NE) have been described as promising alternatives to conventional formulations for increase skin hydration. Besides, these systems have been used as efficient vehicles for lipophilic molecules that improve skin properties (e.g. vitamin E). In this study, we performed comparative investigations between hydrogels formulations containing vitamin E-loaded NLC (HG-NLC_VE) and vitamin E-loaded nanoemulsion (HG-NE_VE). The experiments started with particle size measurements, which showed no significant differences between nanoparticles/nanodroplets sizes after incorporation in the hydrogel net (386 nm vs. 397 nm for HG-NLC_VE and 402 nm vs. 514 nm for HG-NE_VE). Afterwards, in vitro biocompatibility studies in human keratinocytes were carried out, being observed that the lipid-based nanosystems were more cytotoxic for the cells before incorporation in the hydrogel. Finally, the formulations hydration potential and sensory attributes for skin application were evaluated by in vitro occlusion tests and in vivo human experiments. The results showed that the HG-NLC_VE exhibited the best occlusive properties, whereas the HG-NE_VEperformed a faster skin hydration effect. Furthermore, the latter was selected as the most attractive for skin application, although the HG-NLC_VE was described as more suitable to obtain a long-lasting effect. This study demonstrated the in vitro and in vivo safety and hydration potential of hydrogels containing vitamin E-loaded lipid-based nanosystems. These results establish a basis to assess the cutaneous use of these systems, despite more in vivo experiments, for longer periods and in more volunteers, are required before commercialization.

Alzoubi KH, Hasan ZA, Khabour OF, Mayyas FA, Al Yacoub ON, Banihani SA, Alomari MA, Alrabadi NN

Physiol Behav. 2019 Jul 1;206:200-205. doi: 10.1016/j.physbeh.2019.04.011. Epub 2019 Apr 13.

Abstract

Altamura S, Vegi NM, Hoppe PS, Schroeder T, Aichler M, Walch A, Okreglicka K, Hültner L, Schneider M, Ladinig C, Kuklik-Roos C, Mysliwietz J, Janik D, Neff F, Rathkolb B, Hrabé de Angelis M, Buske C, da Silva AR, Muedder K, Conrad M, Ganz T, Kopf M, Muckenthaler MU, Bornkamm GW

Haematologica. 2019 Jun 27. pii: haematol.2018.212977. doi: 10.3324/haematol.2018.212977. [Epub ahead of print]

Abstract

Glutathione peroxidase 4 (GPX4) is unique as it is the only enzyme that can prevent detrimental lipid peroxidation in vivo by reducing lipid peroxides to the respective alcohols thereby stabilizing oxidation products of unsaturated fatty acids. During reticulocyte maturation, 15-lipoxygenase-mediated lipid peroxidation in humans and rabbits and by 12/15-lipoxygenase (ALOX15) in mice had been considered as the initiating event for the elimination of mitochondria which is now known to occur through mitophagy. Yet, genetic ablation of the Alox15 gene in mice failed to provide evidence for this hypothesis. We designed a different genetic approach to tackle this open conundrum. Since either other lipoxygenases or non-enzymatic autooxidative mechanisms may compensate for the loss of Alox15, we asked whether ablation of GPX4 in the hematopoietic system would result in perturbation of reticulocyte maturation. Quantitative assessment of erythropoiesis indices in the blood, bone marrow and spleen of chimeric mice with GPX4 ablated in hematopoietic cells revealed anemia with an increase in the fraction of erythroid precursor cells and reticulocytes. Additional dietary vitamin E depletion strongly aggravated the anemic phenotype. Despite strong extramedullary erythropoiesis reticulocytes failed to mature and accumulated large autophagosomes with engulfed mitochondria. GPX4-deficiency in hematopoietic cells led to systemic hepatic iron overload and simultaneous severe iron demand in the erythroid system. Despite extremely high erythropoietin and erythroferrone levels in the plasma, hepcidin expression remained unchanged. Conclusively, perturbed reticulocyte maturation in response to GPX4 loss in hematopoietic cells thus causes ineffective erythropoiesis, a phenotype partially masked by dietary vitamin E supplementation.

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

Environ Pollut. 2019 Jun 26;252(Pt B):1519-1531. doi: 10.1016/j.envpol.2019.06.092. [Epub ahead of print]

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.

Chai W, Maskarinec G, Franke AA, Monroe KR, Park SY, Kolonel LN, Wilkens LR, Le Marchand L, Cooney RV

Eur J Clin Nutr. 2019 Jun 26. doi: 10.1038/s41430-019-0460-7. [Epub ahead of print]

Abstract

BACKGROUND/OBJECTIVES:

γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality.

SUBJECTS/METHODS:

Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow-up time of 9.6 ± 2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression.

RESULTS:

Positive associations of serum γ-tocopherol with all-cause, cancer, and cardiovascular disease mortality (CVD) (P_trend < 0.05) were detected after adjusting for age, race/ethnicity, and serum cholesterol levels. The respective HRs (95% CIs) for the highest versus the lowest sex-specific γ-tocopherol quartile were 1.43 (1.17-1.74), 1.79 (1.22-2.64), and 1.52 (1.10-2.11) for men and 1.58 (1.25-2.00), 1.59 (1.05-2.41), and 1.59 (1.07-2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR = 1.38; 95% CI = 1.08-1.75; P_trend = 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models, with no interactions between ethnicity and γ-tocopherol.

CONCLUSIONS:

The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions.

Wallert M, Bauer J, Kluge S, Schmölz L, Chen YC, Ziegler M, Searle AK, Maxones A, Schubert M, Thürmer M, Pein H, Koeberle A, Werz O, Birringer M, Peter K, Lorkowski S

Redox Biol. 2019 Jun;24:101166. doi: 10.1016/j.redox.2019.101166. Epub 2019 Mar 12.

Abstract

The plant Garcinia kola is used in African ethno-medicine to treat various oxidation- and inflammation-related diseases but its bioactive compounds are not well characterized. Garcinoic acid (GA) is one of the few phytochemicals that have been isolated from Garcinia kola. We investigated the anti-inflammatory potential of the methanol extract of Garcinia kola seeds (NE) and purified GA, as a major phytochemical in these seeds, in lipopolysaccharide (LPS)-activated mouse RAW264.7 macrophages and its anti-atherosclerotic potential in high fat diet fed ApoE^-/- mice. This study outlines an optimized procedure for the extraction and purification of GA from Garcinia kola seeds with an increased yield and a purity of >99%. We found that LPS-induced upregulation of iNos and Cox2 expression, and the formation of the respective signaling molecules nitric oxide and prostanoids, were significantly diminished by both the NE and GA. In addition, GA treatment in mice decreased intra-plaque inflammation by attenuating nitrotyrosinylation. Further, modulation of lymphocyte sub-populations in blood and spleen have been detected, showing immune regulative properties of GA. Our study provides molecular insights into the anti-inflammatory activities of Garcinia kola and reveals GA as promising natural lead for the development of multi-target drugs to treat inflammation-driven diseases.

Ansariniya H, Hadinedoushan H, Javaheri A, Zare F

J Obstet Gynaecol. 2019 Jun 24:1-6. doi: 10.1080/01443615.2019.1601167. [Epub ahead of print]

Abstract

Endometriosis is an extremely heterogeneous disease and affects about ten percent of the female population during their reproductive years. Recent studies showed that endometriosis is an angiogenesis-dependent disease. Peritoneal macrophages are a well-characterised source of vascular endothelial growth factor (VEGF). The aim of this study was to determine the VEGF gene expression and production in peritoneal macrophages of patients with endometriosis under the effects of vitamins C and E in comparison with control. The lab trial study carried out on 50 patients undergoing laparoscopy and peritoneal fluid samples were collected from them. We compared the VEGF gene expression and production in peritoneal macrophages among groups by using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Our results showed that gene expressions influenced by vitamin C increased in different concentrations and incubation times, except for the incubation time after 48 h. In the case of vitamin E, this was evident with the exception of vitamin E 50 μM after 24 h and vitamin E 100 μM after 48 h. Our findings indicated that vitamin C and E in different concentrations and incubation times altered VEGF gene expression in the peritoneal macrophages but they had not affected on VEGF productions. Impact statement What is already known on this subject? Previous studies showed that antioxidants play a key role in the inhibition of oxidative stress-induced damages and the reduction of pelvic pain in patients with endometriosis. Vitamin E and vitamin C are the main components in neutralising free radicals. Also, antioxidant consumption such as vitamin C and vitamin E in women with endometriosis showed an inverse correlation between antioxidant intake and endometriosis pathology. What do the results of this study add? Vitamin C and E in different concentrations and times of incubation altered vascular endothelial growth factor gene expression and production in peritoneal macrophages. What are the implications of these findings for clinical practice and/or further research? Further studies are needed to determine the effects of C and E vitamins in different concentrations on vascular endothelial growth factor gene expression and production in peritoneal macrophages and the possible roles of these vitamins in treating endometriosis.