Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats’ medial prefrontal cortex induced by acceptable daily dose of aspartame.

Rafati A, Noorafshan A, Jahangir M, Hosseini L, Karbalay-Doust S

Acta Histochem. 2018 Jan;120(1):46-55. doi: 10.1016/j.acthis.2017.11.004. Epub 2017 Nov 21.

Abstract

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons’ number, glial cells number, and rats’ performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes.

Beytut E, Yilmaz S, Aksakal M, Polat S

J Trace Elem Med Biol. 2018 Jan;45:131-135. doi: 10.1016/j.jtemb.2017.10.005. Epub 2017 Oct 16.

Abstract

Acute exposure to high doses of glucocorticoids (GCs) may potentially increase the basal levels of reactive oxygen species (ROS) by altering the defence capacity against oxidative damage. Also, antioxidants may affect the oxidative breakdown of tissues. Therefore, the aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO) as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the brain of rats treated with high doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination of vitamin E and Se, respectively, for 30days. For 3days subsequently, the control (group 1) was treated with a placebo, and the remaining 4 groups were injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se-GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH) and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and reduced GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to 60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to the control levels at 48h. In contrast, prednisolone administration caused an increase in the brain TBARS, reaching up to six times the level of the control at 24h (p<0.001). However, supplementation with vitamin E and Se had a preventive effect on the elevation of the brain TBARS and improved the diminished activities of antioxidative enzymes and the levels of reduced GSH. Therefore, the present study attempts to determine the sequence of cellular membrane damage in the brain of the rats after high doses GC administration and the possible roles in vivo of vitamin E and Se, and their combination.

Baghcheghi Y, Beheshti F, Shafei MN, Salmani H, Sadeghnia HR, Soukhtanloo M, Anaeigoudari A, Hosseini M

Metab Brain Dis. 2017 Dec 30. doi: 10.1007/s11011-017-0176-0. [Epub ahead of print]

Abstract

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P < 0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P < 0.01-P < 0.001). All the effects of PTU were reversed by Vit E (P < 0.01-P < 0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

Bao A, Yang H, Ji J, Chen Y, Bao W, Li F, Zhang M, Zhou X, Li Q, Ben S

Respir Res. 2017 Dec 29;18(1):216. doi: 10.1186/s12931-017-0697-4.

Abstract

BACKGROUND:

Exposure to ambient ozone (O₃) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O₃ to trigger asthma exacerbations are still unclear.

METHODS:

An ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O₃(OVA-O₃ model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O₃ model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant). Biological measurements were conducted including airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL), inflammation in the airway lumen and lung parenchyma, the phosphorylation of p38 MAPK and heat shock protein (HSP) 27 in the tracheal tissues, and the malondialdehyde (MDA) content and the glutathione peroxidase (GSH-Px) activity in lung tissues.

RESULTS:

In OVA-allergic mice, O3 exposure deteriorated airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL) and pulmonary inflammation, accompanied by the increased oxidative stress in lung tissues and promoted p38 MAPK and HSP27 phosphorylation in tracheal tissues. Administration of SB239063 (a p38 MAPK inhibitor) on OVA-O3 model exclusively mitigated the Raw, the CL, and the BAL IL-13 content, while α-tocopherol (antioxidant) differentially reduced the BAL number of eosinophils and macrophages, the content of BAL hyaluronan, the peribronchial inflammation, as well as the mRNA expression of TNF-α and IL-5 in the lung tissues of OVA-O3 model. Administration of these two chemical inhibitors similarly inhibited the AHR, the BAL IFN-γ and IL-6 production, the perivascular lung inflammation and the lung IL-17 mRNA expression of OVA-O3 model. Interestingly, the combined treatment of both compounds together synergistically inhibited neutrophil counts in the BALF and CXCL-1 gene expression in the lung.

CONCLUSIONS:

O₃ exposure during the OVA challenge process promoted exacerbation in asthma. Both p38 MAPK and oxidative stress were found to play a critical role in this process and simultaneous inhibition of these two pathways significantly reduced the O₃-elicited detrimental effects on the asthma exacerbation.

Rios R, Raya AI, Pineda C, Rodriguez M, Lopez I, Aguilera-Tejero E

BMC Nephrol. 2017 Dec 28;18(1):374. doi: 10.1186/s12882-017-0790-4.

Abstract

BACKGROUND:

High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets.

METHODS:

Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half were maintained on basic VitE requirements (27 mg/kg). Thus, rats were allotted to four experimental groups: Nx-NF (n = 8), Nx-NF-VitE (n = 8), Nx-HF (n = 8) and Nx-HF-VitE (n = 8). At the time of sacrifice (day 66), blood and tissue samples were obtained.

RESULTS:

Feeding a HF diet for 45 days did not increase body weight but elicited hyperglycemia, hypertriglyceridemia, an increase in plasma fibroblast growth factor 23 and a reduction in plasma calcitriol concentrations. After Nx, rats fed HF diet showed substantial extraskeletal calcification with aortic calcium content that was higher than in rats fed NF diet. Supplementation with VitE significantly (p < 0.05) reduced aortic (from 38.4 ± 8.8 to 16.5 ± 1.4 mg/g), gastric (from 5.6 ± 2.7 to 1.2 ± 0.4 mg/g) and pulmonary (from 1.8 ± 0.3 to 0.3 ± 0.2 mg/g) calcium content in rats on HF diets.

CONCLUSIONS:

Uremic rats fed HF diets developed more severe extraosseous calcifications than their normocaloric-fed counterparts and dietary VitE supplementation protected against uremic calcifications in rats fed HF diets. Thus, eating energy-rich foods should be discouraged in patients with renal disease and their deleterious effect may be ameliorated with adequate antioxidant supply.

Tian Y, Xiao Y, Wang B, Sun C, Tang K, Sun F

Biosci Rep. 2017 Dec 22. pii: BSR20171003. doi: 10.1042/BSR20171003. [Epub ahead of print]

Abstract

Although fluoride has been widely used in toothpaste, mouthwash, and drinking water to prevent dental caries, the excessive intake of fluoride can cause fluorosis which is associated with dental, skeletal, and soft tissue fluorosis. Recent evidences have drawn the attention to its adverse effects on male reproductive system that include spermatogenesis defect, sperm count loss, and sperm maturation impairment. Fluoride induces oxidative stress through the activation of mitogen activated protein kinase (MAPK) cascade which can lead to cell apoptosis. Vitamin E (VE) and lycopene are two common anti-oxidants, being protective to reactive oxygen species (ROS)-induced toxic effects. However, whether and how these two anti-oxidants prevent fluoride-induced spermatogenic cell apoptosis are largely unknown. In the present study, a male rat model for coal burning fluorosis was established and the histological lesions and spermatogenic cell apoptosis in rat testes were observed. The decreased expression of clusterin, a heterodimeric glycoprotein reported to regulate spermatogenic cell apoptosis, is detected in fluoride-treated rat testes. Interestingly, the co-administration with VE or lycopene reduced fluorosis-mediated testicular toxicity and rescued clusterin expression. Further, fluoride caused the enhanced Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) phosphorylation, which was reduced by VE or lycopene. Thus, VE and lycopene prevent coal burning fluorosis-induced spermatogenic cell apoptosis through the suppression of oxidative stress-mediated JNK and ERK signaling pathway, which could be an alternative therapeutic strategy for the treatment of fluorosis.

Zakaria S, Mat-Husain SZ, Ying-Hwey K, Xin-Kai K, Mohd-Badawi A, Abd-Ghani NA, Aziz MA, Mohamed N

Iran J Basic Med Sci. 2017 Dec;20(12):1360-1367. doi: 10.22038/IJBMS.2017.9610.

Abstract

OBJECTIVES:

Alcohol consumption induces oxidative stress on bone, which in turn increases the risk of osteoporosis. This study determined the effects of vitamin E on bone strength and bone mineral content in alcohol-induced osteoporotic rats.

MATERIALS AND METHODS:

Three months old Sprague Dawley male rats were randomly divided into 5 groups: (I) control group; (II) alcohol (3g/kg) + normal saline; (III) alcohol (3g/kg) + olive oil; (IV) alcohol (3g/kg) + alpha-tocopherol (60mg/kg) and (V) alcohol (3g/kg) + palm vitamin E (60mg/kg). The treatment lasted for three months. Following sacrifice, the right tibia was subjected to bone biomechanical test while the lumbar (fourth and fifth lumbar) and left tibia bones were harvested for bone mineral measurement.

RESULTS:

Alcohol caused reduction in bone biomechanical parameters (maximum force, ultimate stress, yield stress and Young’s modulus) and bone minerals (bone calcium and magnesium) compared to control group (P<0.05). Palm vitamin E was able to improve bone biomechanical parameters by increasing the maximum force, ultimate stress and Young’s modulus (P<0.05) while alpha-tocopherol was not able to. Both alpha-tocopherol and palm vitamin E were able to significantly increase tibia calcium and magnesium content while only alpha-tocopherol caused significant increase in lumbar calcium content (P<0.05).

CONCLUSION:

Both palm vitamin E and alpha-tocopherol improved bone mineral content which was reduced by alcohol. However, only palm vitamin E was able to improve bone strength in alcohol treated rats.

Sun B, Zhang X, Yin Y, Sun H, Ge H, Li W

J Trace Elem Med Biol. 2017 Dec;44:88-92. doi: 10.1016/j.jtemb.2017.06.004.

Abstract

OBJECT:

To investigate the effects of sulforaphane (SFN) and vitamin E (VE) on spatial learning and memory ability and oxidative damage of hippocampus in lead-exposed mice at lactation.

METHODS:

A total of 18 adult Kunming mice, all 12 female mice were divided into two groups by body weight randomly, 10 mice drank water containing 0.2% lead acetate at lactation, the other 2 mice drank lead free deionized water named as the normal group. Then, they were mated at a 1:2 ratio of male to female. After weaning, the pups were divided into 5 groups by weight randomly (10 each group): normal saline (NS) group, corn oil (CO) group, SFN group, VE group and SFN+VE group. They were subject to gavage daily for four weeks. Gavage doses of SFN and VE were 25mg/kg and 30 IU/kg respectively. Meanwhile, 10 pups of the normal group were selected randomly as the control (C) group. The C group was normally raised for 4 weeks. The spatial learning and memory ability of them were evaluated by the Morris water maze test, and the lead level in the blood was determined by polarography. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in hippocampus were measured by the kits.

RESULTS:

Compared with the NS and CO groups, the lead level in the blood of SFN and SFN+VE group had a significant decrease. In water maze test, the mice treated with SFN or/and VE performed better than mice of the NS and CO groups. In addition, a remarkable decrease in MDA level was found in mice treated with SFN or/and VE than those in NS and CO groups. What’s more, there was no statistical distinction of SOD activity in SFN group than that of NS group. SOD activity significantly increased was observed in VE and SFN+VE groups than that of CO group.

CONCLUSION:

Sulforaphane and vitamin E could ameliorate cognitive decline and oxidative damage in pups with lead exposure at lactation from maternal milk.

Wajid N, Azam M, Khalid S, Ali F, Qazi A, Qazi MH

J Coll Physicians Surg Pak. 2017 Dec;27(12):754-758. doi: 2766.

Abstract

OBJECTIVE:

To assess the role of Vitamin E to improve the survival of Wharton’s jelly derived mesenchymal stem cells (WJMSCs) in breast cancer conditions.

STUDY DESIGN:

An experimental study.

PLACE AND DURATION OF STUDY:

Centre for Research in Molecular Medicine, University of Lahore, from November 2016 to March 2017.

METHODOLOGY:

WJMSCs were obtained from umbilical cord tissue with enzyme digestion method. Isolated cells were characterized for CD90 and CD45 by immunocytochemistry. Pretreatment and conjugation therapies of vitamin E in 50mM and 100mM concentration were used on WJMSCs and breast cancer plasma was provided to mimic the cancer conditions, while WJMSCs provided with normal plasma were considered control. Cells’ viability, proliferation and death were evaluated by crystal violet staining, MTT assay and LDH assay, respectively. Oxidative stress was observed by activity of anti-oxidant enzymes (GSH, catalase, SOD) and reactive oxygen species (MDA).

RESULTS:

The isolated cells expressed mesenchymal stem cells marker CD90 and lacked hematopoietic marker CD45. Vitamin E improved the viability and proliferation of WJMSCs in normal plasma, in conjugation with breast cancer plasma and in pretreatment groups but conjugation group showed even better results with concentration of 100mM as compared to the pretreatment group and opposite was observed for LDH assay for cells death analysis. Vitamin E also reduced the oxidative stress in 100mM more pronounced in conjugation group as compared to pretreatment group while left no harmful effects on WJMSCs in normal plasma.

CONCLUSION:

Vitamin E conjugation with breast cancer conditions significantly improved growth of WJMSCs. Thus vitamin E treated WJMSCs are better therapeutic options for breast cancer.

Das Gupta S, Patel M, Wahler J, Bak MJ, Wall B, Lee MJ, Lin Y, Shih WJ, Cai L, Yang CS, Suh N

Cancer Prev Res (Phila). 2017 Dec;10(12):694-703. doi: 10.1158/1940-6207.CAPR-17-0190. Epub 2017 Sep 28.

Abstract

Despite experimental evidence elucidating the antitumor activities of tocopherols, clinical trials with α-tocopherol (α-T) have failed to demonstrate its beneficial effects in cancer prevention. This study compared the chemopreventive efficacy of individual tocopherols (α-, δ-, and γ-T) and a γ-T-rich tocopherol mixture (γ-TmT) in the August-Copenhagen Irish (ACI) rat model of estrogen-mediated mammary cancer. Female ACI rats receiving 17β-estradiol (E2) implants were administered with 0.2% α-T, δ-T, γ-T, or γ-TmT for 30 weeks. Although α-T had no significant effects on mammary tumor growth in ACI rats, δ-T, γ-T, and γ-TmT reduced mammary tumor volume by 51% (P < 0.05), 60% (P < 0.01), and 59% (P < 0.01), respectively. Immunohistochemical analysis revealed that δ-T, γ-T, and γ-TmT reduced levels of the cell proliferation marker, proliferating cell nuclear antigen, in the rat mammary tumors. To gain further insight into the biological functions of different forms of tocopherols, RNA-seq analysis of the tumors was performed. Treatment with γ-T induced robust gene expression changes in the mammary tumors of ACI rats. Ingenuity Pathway Analysis identified “Cancer” as a top disease pathway and “Tumor growth” and “Metastasis” as the top signaling pathways modulated by γ-T. Although the results need further functional validation, this study presents an unbiased attempt to understand the differences between biological activities of individual forms of tocopherols at the whole transcriptome level. In conclusion, δ-T and γ-T have superior cancer preventive properties compared to α-T in the prevention of estrogen-mediated mammary carcinogenesis.