OBJECTIVE:

Oxidative stress and dysregulated antioxidant defence may be involved in the pathophysiology of schizophrenia. In the present study, we investigated changes in antioxidants and oxidative stress from an acute to a later stable phase. We hypothesised that the levels of oxidative markers are increased in schizophrenia compared with healthy controls; change from the acute to the stable phase; and are associated with the levels of membrane polyunsaturated fatty acids (PUFAs) and symptom severity.

METHODS:

Fifty-five patients with schizophrenia spectrum disorders, assessed during an acute phase and 5 years later during a stable phase, and 51 healthy controls were included. We measured antioxidants (α-tocopherol, uric acid, albumin and bilirubin), markers of oxidative stress (F2-isoprostane and reactive oxygen metabolites) and membrane fatty acids. Antioxidants and oxidative stress markers were compared in schizophrenia versus healthy controls, adjusting for differences in sex, age and smoking, and changes over time. Associations between symptoms and PUFA were also investigated.

RESULTS:

In the acute phase, α-tocopherol was significantly higher (p < 0.001), while albumin was lower (p < 0.001) compared with the stable phase. Changes in α-tocopherol were associated with PUFA levels in the acute phase. In the stable phase, schizophrenia patients had higher uric acid (p = 0.009) and lower bilirubin (p = 0.046) than healthy controls. CRP was higher in patients in the stable phase (p < 0.001), and there was no significant change from the acute phase.

CONCLUSION:

The present findings of change in antioxidant levels in the acute versus stable phase of schizophrenia the present findings suggest that redox regulation is dynamic and changes during different phases of the disorder.

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Vitamin E has been proposed as a potential clinical intervention for Alzheimer’s disease (AD) given the plausibility of its various biological functions in influencing the neurodegenerative processes associated with the condition. The tocopherol and tocotrienol isoforms of vitamin Ehave multiple properties including potent antioxidant and anti-inflammatory characteristics, in addition to influences on immune function, cellular signalling and lowering cholesterol. Several of these roles offer a theoretical rationale for providing benefit for the treatment of AD-associated pathology. Diminished circulating concentrations of vitamin E have been demonstrated in individuals with AD. Reduced plasma levels have furthermore been associated with an increased risk of AD development while intake, particularly from dietary sources, may limit or reduce the rate of disease progression. This benefit may be linked to synergistic actions between vitamin E isoforms and other micronutrients. Nevertheless, randomised trials have found limited and inconsistent evidence of vitamin E supplementation as an effective clinical intervention. Thus, despite a strong rationale in support of a beneficial role for vitamin E for the treatment of AD, the evidence remains inconclusive. Several factors may partly explain this discrepancy and represent the difficulties of translating complex laboratory evidence and dietary interactions into clinical interventions. Methodological design limitations of existing randomised trials and restrictions to supplementation with a single vitamin E isoform may also limit the influence of effect. Moreover, several factors influence individual responsiveness to vitamin E intake and recent findings suggest variation in the underlying genetic architecture attenuates vitamin E biological availability and activity which likely contributes to the variation in clinical responsiveness and the failure of randomised trials to date. Importantly, the clinical safety of vitamin E remains controversial and warrants further investigation.

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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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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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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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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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