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Figure3: Protein carbonyl contents in rat brains with and without TRF supplementation. There was no significant difference in the level of protein carbonyl between young and older groups. TRF supplementation significantly reduced the level of protein carbonyl. Data is presented as mean ± SEM (n=6). Similar alphabets, a and b, denote significant difference between the groups (p<0.05).  

Figure3: Protein carbonyl contents in rat brains with and without TRF supplementation. There was no significant difference in the level of protein carbonyl between young and older groups. TRF supplementation significantly reduced the level of protein carbonyl. Data is presented as mean ± SEM (n=6). Similar alphabets, a and b, denote significant difference between the groups (p<0.05).  

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Introduction: Tocotrienol exerts neuroprotective effects resulting in an improved circulating oxidative status. However, accumulation of tocotrienol due to long-term intake may exert pro-oxidant effects. Thus the effects of short-and long-term supplementation of vitamin E tocotrienol rich fraction (TRF) on the parameters of oxidative status in rat...

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... 12,13 On the other hand, excess and long-term supplementation of T3 may cause a build-up of itself and potentially may have prooxidant and even neurotoxic effects in vitro. 12,14 Thalamic dysfunction is linked to alcohol abuse. 15 The thalamic area is reported to be susceptible to neurodegenerative diseases 16 and oxidative stress. ...
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Background: Functional deterioration of thalamic structures has been reported in many occasions of ethanol-induced neurodegeneration. Neuroprotective role of Tocotrienol (T3) is well established along with its antioxidant property. Interaction of oral T3 supplementation modalities with the thalamic oxidative stress parameters were studied in low-to-moderate doses of ethanol (Et) exposures. Materials and Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), prior supplementation (PT3), simultaneous supplementation (ST3) and total supplementation (TT3) with T3 for 6 weeks. Thalamic levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were estimated. Results: Two-way ANOVA demonstrated that all the thalamic GSH and LPO were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of only LPO level of thalamus. Conclusion: Out of the tested modalities, best protection in terms of oxidative stress was observed when prior and simultaneous supplementation modalities were combined (TT3).
... Both CAT and GSH are antioxidants which are1 responsible for the reduction of the peroxides that are produced from the reaction catalyzed by SOD. Therefore, the consumption of GSH might be sufficient to meet the brain needs (Musalmah et al. 2013). Moreover, in rat brain, the catalase mRNA is present in a high level in the cytoplasm of neuronal cells with heterogeneous distribution pattern along with different subsets of neuron in the brain of rat (Schad et al. 2003). ...
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Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant, where some reports claimed their anti-inflammatory, cytotoxic, and antituberculosis effects, without investigating its role on the brain. Therefore, forty mature male rats were equally divided into 4 groups; the 1st was kept as control. Rats in groups 2 and 4 were orally given P. odorata extract daily at a dose of 500 mg/kg B.W., while those in groups 3 and 4 were daily administrated aluminum chloride “AlCl3” (70 mg/kg B.W.). The treatments extended for 30 successive days. At the end of the experimental period, brain samples were collected for biochemical assay of glutathione reductase (GSH), catalase, malondialdehyde (MDA), and acetylcholinesterase activity (AChE). Besides, monoamines (norepinephrine, dopamine, serotonin), amino acids (glutamine, serine, arginine, taurine and gamma-aminobutyric acid (GABA)), neurotransmitters, DNA damage, cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α genes were estimated. Moreover, brain samples were obtained for histopathological investigation. Aluminum toxicity resulted in a decline of GSH concentration, elevation of MDA, and AChE activity. Except for GABA which exhibited a significant decrease, there was a marked increase in the measured amino acid and monoamine neurotransmitters. Also, an increase in mRNA expressions of TNF-α and COX-2 was detected. It was noticed that Premna odorata extract reduced the oxidative stress and counteracted the augmentations in AChE caused by AlCl3. Marked improvements in most measured neurotransmitters with downregulation of pro-inflammatory gene expression were recorded in P. odorata + AlCl3 group. Premna odorata restores the altered histopathological feature induced by AlCl3. In conclusion, the present findings clarify that P. odorata extract could be important in improving and treatment of neurodegenerative disorders as it was able to reduce oxidative stress, DNA damage, biochemical alterations, and histopathological changes in rats exposed to AlCl3 toxicity.
... [19] With prolonged use, accumulation of T3 is possible and T3 may act as pro-oxidant and even neurotoxic in vitro. [19,20] Hence, the current study evaluates the efficacy of varied modalities of T3 supplementation against the cerebellar oxidative stress because of low-to-moderated doses of Et exposure and appraises the superoxide and peroxide handling capacities (SPHC) of cerebellum in such conditions. ...
... [51] Similarly, in a study with 3 months and 8 months of TRF supplementation, no alteration in brain catalase was observed. [20] Considering the crucial role of catalase in Et metabolism and generation of oxidative stress and with the report of highest level of catalase mRNA expression cerebellum of rat, [44] detailed study of catalase with different levels of Et exposure and antioxidant supplementation is required. Keeping the SOD expression unaltered, pretreatment with T3 increased the gastric mucosal SOD activity in response to stress. ...
... Both 3 months and 8 months of TRF supplementation increased the brain SOD activity of aged rats without much difference between the increments done by these supplementation schedules. [20] They also noticed differential response of catalase and SOD activities in response to TRF supplementation. In the present study, cerebellar SOD activity of TT3 group was significantly raised in comparison to the NT3 group in all the Et phases. ...
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Background and Objectives: Self-intoxication with Ethanol (Et) is a common problem worldwide. Being a psychoactive drug, neurotoxic effects of Et are well known. Cerebellum is highly vulnerable to Et exposure. Tocotrienols (T3) are relatively rare components of vitamin E and have the potential to prevent the oxidative stress and act as neuroprotective. Varied modalities of T3 supplementations were evaluated to identify the possibilities of countering cerebellar oxidative stress caused by low-to-moderate doses of Et exposure. Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), Prior Supplementation (PT3), Simultaneous Supplementation (ST3) and Total Supplementation (TT3) with T3 for 6 weeks. Cerebellar levels of reduced Glutathione (GSH), Lipid Peroxidation (LPO) and activities of catalase, Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) were estimated and Superoxide and Peroxide Handling Capacities (SPHCs) were calculated. Results: All the tested cerebellar oxidative stress parameters and handling capacities were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of LPO level, GPx activity, GR activity and glutathione-dependent SPHC of cerebellum. Conclusion: Critical evaluation of studied parameters suggest insufficient overall performance of ST3 type of supplementation, whereas, TT3 type of supplementation was the best among the modalities of T3 supplementation. However, excess T3 supplementation may not be beneficial in some cases of oxidative stress parameters and SPHC of cerebellum.
... [19] With prolonged use, accumulation of T3 is possible and T3 may act as pro-oxidant and even neurotoxic in vitro. [19,20] Hence, the current study evaluates the efficacy of varied modalities of T3 supplementation against the cerebellar oxidative stress because of low-to-moderated doses of Et exposure and appraises the superoxide and peroxide handling capacities (SPHC) of cerebellum in such conditions. ...
... [51] Similarly, in a study with 3 months and 8 months of TRF supplementation, no alteration in brain catalase was observed. [20] Considering the crucial role of catalase in Et metabolism and generation of oxidative stress and with the report of highest level of catalase mRNA expression cerebellum of rat, [44] detailed study of catalase with different levels of Et exposure and antioxidant supplementation is required. Keeping the SOD expression unaltered, pretreatment with T3 increased the gastric mucosal SOD activity in response to stress. ...
... Both 3 months and 8 months of TRF supplementation increased the brain SOD activity of aged rats without much difference between the increments done by these supplementation schedules. [20] They also noticed differential response of catalase and SOD activities in response to TRF supplementation. In the present study, cerebellar SOD activity of TT3 group was significantly raised in comparison to the NT3 group in all the Et phases. ...
Article
Full-text available
Background: Self-intoxication with ethanol (Et) is a common problem worldwide. Being a psychoactive drug, neurotoxic effects of Et are well known. Cerebellum is highly vulnerable to Et exposure. Tocotrienols (T3) are relatively rare components of vitamin E and have the potential to prevent the oxidative stress and act as neuroprotective. Varied modalities of T3 supplementations were evaluated to identify the possibilities of countering cerebellar oxidative stress caused by low-to-moderate doses of Et exposure. Materials and Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), prior supplementation (PT3), simultaneous supplementation (ST3) and total supplementation (TT3) with T3 for 6 weeks. Cerebellar levels of reduced glutathione (GSH), lipid peroxidation (LPO) and activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were estimated, and superoxide and peroxide handling capacities (SPHCs) were calculated. Results: All the tested cerebellar oxidative stress parameters and handling capacities were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of LPO level, GPx activity, GR activity and glutathione-dependent SPHC of cerebellum. Discussion: Critical evaluation of studied parameters suggest insufficient overall performance of ST3 type of supplementation, whereas, TT3 type of supplementation was the best among the modalities of T3 supplementation. However, excess T3 supplementation may not be beneficial in some cases of oxidative stress parameters and SPHC of cerebellum. Conclusion: Supplementation with T3 was very effective in countering the cerebellar oxidative stress caused by low-to-moderate doses of Et exposure; nevertheless, the modality of supplementation must be employed carefully to obtain the best out of it.
... The vitamin E in HDFs cells was extracted out by the following procedure as previously described with modification to allow vitamin E extraction from the cells 60 . The HDFs cells in culture dish were washed with PBS solution and harvested with accutase (PAA, Austria). ...
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Tocotrienol-rich fraction (TRF) is palm vitamin E that consists of tocopherol and tocotrienol. TRF is involved in important cellular regulation including delaying cellular senescence. A key regulator of cellular senescence, Sirtuin 1 (SIRT1) is involved in lipid metabolism. Thus, SIRT1 may regulate vitamin E transportation and bioavailability at cellular level. This study aimed to determine the role of SIRT1 on cellular uptake and bioavailability of TRF in human diploid fibroblasts (HDFs). SIRT1 gene in young HDFs was silenced by small interference RNA (siRNA) while SIRT1 activity was inhibited by sirtinol. TRF treatment was given for 24 h before or after SIRT1 inhibition. Cellular concentration of TRF isomers was determined according to the time points of before and after TRF treatment at 0, 24, 48, 72 and 96 h. Our results showed that all tocotrienol isomers were significantly taken up by HDFs after 24 h of TRF treatment and decreased 24 h after TRF treatment was terminated but remained in the cell up to 72 h. The uptake of α-tocopherol, α-tocotrienol and β-tocotrienol was significantly higher in senescent cells as compared to young HDFs indicating higher requirement for vitamin E in senescent cells. Inhibition of SIRT1 gene increased the uptake of all tocotrienol isomers but not α-tocopherol. However, SIRT1 inhibition at protein level decreased tocotrienol concentration. In conclusion, SIRT1 may regulate the cellular uptake and bioavailability of tocotrienol isomers in human diploid fibroblast cells while a similar regulation was not shown for α-tocopherol.
Article
Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.