Effect of atherosclerosis and the protective effect of the antioxidant vitamin E on the rabbit cerebellum

Elbeltagy MAF, Elkholy WB, Salman AS

Microscopy (Oxf). 2019 Jul 15. pii: dfz023. doi: 10.1093/jmicro/dfz023. [Epub ahead of print]

Abstract

BACKGROUND:

Atherosclerosis is a major cardiovascular disease and one of the commonest causes of mortality in the world. Speech, balance, fine motor control and cognition are affected by atherosclerosis of cerebellar arteries. This study investigated the protective role of vitamin E against induced atherosclerosis in the rabbit cerebellum.

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Vitamin E modifies high-fat diet-induced reduction of seizure threshold in rats: Role of oxidative stress

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.

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α-Tocopherol Restriction Dysregulates Neurogenesis-Related Gene Expression in Brains of Weanling α-Tocopherol Transfer Protein Knockout Mice (P11-134-19)

Ranard K, Kuchan M, Erdman J Jr

Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz048.P11-134-19. doi: 10.1093/cdn/nzz048.P11-134-19. eCollection 2019 Jun.

Abstract

OBJECTIVES:

Humans with vitamin E (α-tocopherol, αT) deficiency develop neurological disorders. Similarly, α-tocopherol transfer protein knockout (Ttpa-/- ) mice have low vitamin E status and exhibit neurodegeneration with age. Shifts in the transcriptome may precede behavioral manifestations of vitamin E deficiency, but it is unknown how early abnormalities occur. Aberrations during brain development could have lifelong implications. The study objective was to determine how αT restriction during early-life affects the expression of pre-selected neurogenesis-related genes in the cerebellum (CB) and cerebral cortex (CC) of Ttpa-/- weanlings.

METHODS:

Female Ttpa+/+ (n = 9) and Ttpa-/- (n = 10) mice were nursed by Ttpa+/- dams until postnatal day 21. Dams were fed AIN-93G diet (75 mg αT/kg diet) during days 1-9 of gestation, and αT-stripped diet for the rest of the study. Homogenized brain tissues from 21 day old weanlings were used to measure αT concentrations via HPLC-PDA. The expression of genes critical for brain development (RoraShh), myelination (Plp1, Cntnap1, Mbp, Mobp, Nr1h3), synaptic function (Cplx1, Cplx2, Vamp2, Necab1, Prkcg), and αT cellular uptake (Scarb1) were measured in the CB and CC via real-time qPCR.

RESULTS:

αT levels were significantly decreased in brains of Ttpa-/- mice (0.1 ± 0.1 nmol/g) compared to Ttpa+/+ mice (9.8 ± 1.4 nmol/g) (P < 0.001), confirming their low αT status. RoraShhCntnap1, and Mbp were significantly upregulated (P < 0.05) in both the CB and CC of Ttpa-/- mice, while several genes were only upregulated in one brain region (Plp1 in the CB, Mobp in the CC). Necab1 and Scarb1 were significantly downregulated in the CB of Ttpa-/- mice (P < 0.05).

CONCLUSIONS:

αT restriction during the fetal and postnatal periods alters the expression of neurogenesis-related genes. These findings support a role for αT in brain development.

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Vitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19)

Park HA, Mnatsakanyan N, Broman K, Jonas E

Curr Dev Nutr. 2019 Jun 13;3(Suppl 1). pii: nzz052.P14-024-19. doi: 10.1093/cdn/nzz052.P14-024-19. eCollection 2019 Jun.

Abstract

OBJECTIVES:

B-cell lymphoma-extra large (Bcl-xL) is a pro-survival protein localized to mitochondria. Bcl-xL is reported to support brain function by enhancing neuronal energy metabolism, synapse formation, and neurite outgrowth. However, under exposure to excitotoxic stimulation and subsequent oxidative stress, Bcl-xL undergoes caspase dependent cleavage to ∆N-Bcl-xL. Accumulation of ∆N-Bcl-xL is associated with neuronal death; thus, approaches that prevent ∆N-Bcl-xL accumulation protect neurons from excitotoxic insult. In this study, we hypothesize that ∆N-Bcl-xL formation is regulated by redox status in mitochondria. We thus tested if production of ∆N-Bcl-xL can be inhibited by the fat-soluble antioxidant α-tocotrienol (TCT) given its ability to scavenge free radicals produced in the mitochondrial membrane.

METHODS:

Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both, and mitochondrial oxidative stress, mitochondrial potential, caspase activity, and ∆N-Bcl-xL protein levels were quantified.

RESULTS:

Glutamate caused abnormalities in mitochondrial function leading to neuronal death. The antioxidant α-TCT protected neurons from glutamate-induced mitochondrial dysfunction and cytotoxicity. α-TCT treatment protected against cleavage of full length anti-apoptotic Bcl-xL to form pro-death ∆N-Bcl-xL. α-TCT significantly attenuated glutamate-induced reactive oxygen species (ROS) formation, caspase 3 activation and ∆N-Bcl-xL formation at mitochondria.

CONCLUSIONS:

Our data suggests that oxidative stress production during excitotoxicity is responsible for the formation of ∆N-Bcl-xL. Thus, application of a lipophilic antioxidant such as vitamin E is neuroprotective by improving mitochondrial redox status and preventing production of neurotoxic ∆N-Bcl-xL.

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Protective potential of Vitamin E against methylphenidate-induced male gonadal changes in albino rats.

Iqbal S, Hameed U, Hasan B, Zia-Ul-Islam, Ahmed M, Brohi AH

Int J Health Sci (Qassim). 2019 May-Jun;13(3):19-23.

Abstract

OBJECTIVE:

Attention deficit hyperactivity disorder ranks among the top neuropsychiatric disorder of childhood and adolescents. Methylphenidate (MPH) is the most frequently used pharmacologic agent to treat this condition. Its long-term use has been associated with many unwanted and adverse effects on many organs including male gonads, but so far no study has been done to find out a protective agent. This study investigated the protective potential of Vitamin E (Vit E) against the microscopic and morphometric alterations in male gonads induced by MPH, using albino rats.

METHODS:

Adult male albino rats were assigned into three equal groups including one control and two experimental groups. Experimental groups administered with MPH (10 mg/kg) and MPH (10 mg/kg) + Vit E orally (50 mg/kg), daily for 40 days. Testes of the sacrificed animals were removed, processed, and stained with hematoxylin and eosin for examining the microscopic and morphometric alterations and protective potential of Vit E. Data were analyzed using ANOVA.

RESULTS:

Experimental animals treated with MPH showed a significant decrease in the diameter of seminiferous tubules (296.86 ± 14.70 µm) and height of germinal epithelium (51.73 ± 3.15 µm) with a corresponding gain in the thickness of the interstitium (47.05 ± 4.94 µm). Animals treated with MPH + Vit E did not reveal any significant testicular microscopic changes and seminiferous tubular alterations induced by MPH.

CONCLUSION:

Vit E demonstrated a protective potential against the adverse changes induced by MPH in the male gonads in albino rats.

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Vitamin E status in healthy population in Asia: a review of current literature

Malik A, Eggersdorfer M, Trilok-Kumar G

Int J Vitam Nutr Res. 2019 May 24:1-14. doi: 10.1024/0300-9831/a000590. [Epub ahead of print]

Abstract

Vitamin E is a lipid soluble antioxidant which mainly circulates as α-tocopherol in the human plasma. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions. Although substantial data on vitamin E status has been published worldwide, there is paucity of data on the extent of deficiency from most Asian countries, including India. Part of the problem is lack of validated biomarkers for vitamin E and no consensus on cut offs for defining deficiency and sufficiency. Thus, interpretation of the data on the vitamin E status is difficult. Limited available data from 31 studies on vitamin E status in healthy people from Asia, the most populated continent, has been collated for the purpose of this review. Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs. The findings are not surprising as both, vitamin E intakes and its status have not received too much attention in the past. Lack of conclusive data accentuates the need for more research on the vitamin E status across all age groups and to define age, gender and physiological state specific cut offs for vitamin E levels.

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Transcriptomic Analysis of MAPK Signaling in NSC-34 Motor Neurons Treated with Vitamin E

Chiricosta L, Gugliandolo A, Tardiolo G, Bramanti P, Mazzon E

Nutrients. 2019 May 15;11(5). pii: E1081. doi: 10.3390/nu11051081.

Abstract

Vitamin E family is composed of different tocopherols and tocotrienols that are well-known as antioxidants but that exert also non-antioxidant effects. Oxidative stress may be involved in the progression of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), characterized by motor neuron death. The aim of the study was the evaluation of the changes induced in the transcriptional profile of NSC-34 motor neurons treated with α-tocopherol. In particular, cells were treated for 24 h with 10 µM α-tocopherol, RNA was extracted and transcriptomic analysis was performed using Next Generation Sequencing. Vitamin E treatment modulated MAPK signaling pathway. The evaluation revealed that 34 and 12 genes, respectively belonging to “Classical MAP kinase pathway” and “JNK and p38 MAP kinase pathway”, were involved. In particular, a downregulation of the genes encoding for p38 (Log2 fold change -0.87 and -0.67) and JNK (Log2 fold change -0.16) was found. On the contrary, the gene encoding for ERK showed a higher expression in cells treated with vitamin E (Log2 fold change 0.30). Since p38 and JNK seem more involved in cell death, while ERK in cell survival, the data suggested that vitamin E treatment may exert a protective role in NSC-34 motor neurons. Moreover, Vitamin E treatment reduced the expression of the genes which encode proteins involved in mitophagy. These results indicate that vitamin E may be an efficacious therapy in preventing motor neuron death, opening new strategies for those diseases that involve motor neurons, including ALS.

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Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus

Nesari A, Mansouri MT, Khodayar MJ, Rezaei M

Nutr Neurosci. 2019 May 14:1-11. doi: 10.1080/1028415X.2019.1601888. [Epub ahead of print]

Abstract

OBJECTIVE:

The ubiquitin-proteasome system plays a key role in memory consolidation. Proteasome inhibition and free radical-induced neural damage were implicated in neurodegenerative states. In this study, it was tested whether alpha-tocopherol (αT) in low and high doses could improve the long-term memory impairment induced by proteasome inhibition and protects against hippocampal oxidative stress.

METHODS:

Alpha-tocopherol (αT) (60, 200 mg/kg, i.p. for 5 days) was administered to rats with memory deficit and hippocampal oxidative stress induced by bilateral intra-hippocampal injection of lactacystin (32 ng/μl) and mitochondrial evaluations were performed for improvement assessments.

RESULTS:

The results showed that lactacystin significantly reduced the passive avoidance memory performance and increased the level of malondialdehyde (MDA), reactive oxygen species (ROS) and diminished the mitochondrial membrane potential (MMP) in the rat hippocampus. Furthermore, Intraperitoneal administration of αT significantly increased the passive avoidance memory, glutathione content and reduced ROS, MDA levels and impaired MMP.

CONCLUSIONS:

The results suggested that αT has neuroprotective effects against lactacystin-induced oxidative stress and memory impairment via the enhancement of hippocampal antioxidant capacity and concomitant mitochondrial sustainability. This finding shows a way to prevent and also to treat neurodegenerative diseases associated with mitochondrial impairment.

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Vitamin E and Alzheimer’s disease: the mediating role of cellular aging

Casati M, Boccardi V, Ferri E, Bertagnoli L, Bastiani P, Ciccone S, Mansi M, Scamosci M, Rossi PD, Mecocci P, Arosio B

Aging Clin Exp Res. 2019 May 3. doi: 10.1007/s40520-019-01209-3. [Epub ahead of print]

Abstract

BACKGROUND:

Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer’s disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects.

AIM:

Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD.

METHODS:

53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, β-, γ- and δ-tocopherol, α-, β-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured.

RESULTS AND DISCUSSION:

Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, β-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and β-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging.

CONCLUSIONS:

Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.

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Vitamin E modifies high-fat diet-induced reduction of seizure threshold in rats: Role of oxidative stress

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

Physiol Behav. 2019 Apr 13;206:200-205. doi: 10.1016/j.physbeh.2019.04.011. [Epub ahead of print]

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.

Read More

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