Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition

BACKGROUND: The mechanism of aluminum-induced neurotoxicity is not clear. The involvement of glutamate in the aluminium-induced neurocomplications has been suggested. Brain glutamate levels also found to be altered in protein malnutrition. Alterations in glutamate levels as well as glutamate-α-decarboxylase in different regions of rat brain has been reported in response to aluminum exposure. Thus the study of glutamate metabolising enzymes in different brain regions of rats maintained on either normal or restricted protein diet may be of importance for understanding the neurotoxicity properties of aluminium. RESULTS: Dietary protein restrictions does not have an significant impact on regional aluminum content of the brain. The interaction of aluminum intoxication and protein restriction is significant in the thalamic area and the midbrain-hippocampal region in cases of glutamate oxaloacetate transaminase. In the case of gluatmate pyruvate transaminase, this interaction is significant only in thalamic area. CONCLUSION: The metabolism of amino acids, as indicated by activities of specific transaminases, of brain is altered in response to aluminum exposure. These alterations are region specific and are dependent on dietary protein intake or manipulation of the brain amino acid homeostasis

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

BACKGROUND: Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. RESULTS: Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. CONCLUSION: The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders

EFFECT OF TOCOTRIENOL PRETREATMENT ON EX VIVO SUPEROXIDE AND PEROXIDE HANDLING CAPACITIES (SPHC) OF RAT SERUM AND BRAIN

Objective: Tocotrienol (TT), a constituent of vitamin E, present only in selected seed oil. Because of the isoprenoid side chain, antioxidant property of tocotrienol is recently highlighted. Application of tocotrienol is also proven to be neuroprotective. The current study was aimed to evaluate the effect of tocotrienol pretreatment on the serum and brain oxidative stress parameters and oxidant handling capacities.Methods: Male albino Wistar rats were treated with tocotrienol (10 mg/day) for two weeks and maintained for the next four weeks. Levels of reduced glutathione and lipid peroxidation and activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were estimated fortnightly in serum. After sacrifice, oxidative stress parameters were measured in the frontal cortex, temporal cortex, thalamic area, hippocampus and cerebellum. Glutathione-dependent and glutathione-independent superoxide and peroxide handling capacities (SPHC) were calculated for serum and brain regions. Data collected from both the groups are statistically processed with Kruskal-Wallis test and Mann-Whitney pairwise comparisons.Results: Significant impacts of TT treatment have been observed in terms of growth and water intake. Serum SPHC (Glutathione-independent) has been found to be reduced significantly immediately after the TT treatment. Region-specific alterations in oxidative stress parameters have also been observed after 4 w of supplementation. Global reductions in reduced glutathione and lipid peroxidation have been observed in the brain without any alteration in the SPHC.Conclusion: From the results, it can be suggested that the tocotrienol pretreatment possibly be used as neuroprotective measure particularly against oxidative stress. In addition, the antioxidant impacts of TT were found to be maintained for a longer period in brain regions, even though it was not so in the case of serum

TOCOTRIENOL OPPOSES THE EFFECT OF LIGHT TO MODERATE ETHANOL EXPOSURES IN ELEVATED PLUS MAZE PERFORMANCE OF RATS

ABSTRACTObjective: Tocotrienol is a naturally rare isoform of vitamin E. Consumption of ethanol is a common problem. Ethanol acts as an anxiolytic, buthastens cognitive problems. The current study is aimed to evaluate the effect of tocotrienol against ethanol-induced cognitive and anxiolytic behavior.Methods: Male albino Wistar rats were divided into two sets; one set of rats were exposed with low-to-moderate doses of ethanol for 4 weeks, whileanother set was exposed to tocotrienol orally (10 mg/day) plus low-to-moderate doses of ethanol for 4 weeks. Performances of rats on elevatedplus maze were carried out at the end of the treatment protocol for 3 days. Video recordings were analyzed for acquisition time, retention time, andnumber of entries to open arms and closed arms. Numbers of protected stretch attend posture, unprotected stretch attend posture, protected headdipping, unprotected head dipping, grooming, rearing, paw licking, immobile sniffing, and fecal boli were also counted from the video recording.Results: Statistically significant influences of tocotrienol and ethanol exposures have been observed in aquisition time and retention time after24 hrs and 48 hrs, respectively. Number of exits from the closed arms and grooming and rearing behaviors also found to be significantly influencedby tocotrienol treatment.Conclusion: From the current study, it can be concluded that tocotrienol facilitates the explorative behaviors of control rats. In addition, the currentprotocol of tocotrienol treatment opposes the ethanol-induced cognitive impairment as well as ethanol-induced anxiolytic activity in rats.Keywords: Tocotrienol, Ethanol, Elevated plus maze, Acquisition time, Retention time, Protected stretch attend posture, Unprotected stretch attendposture, Protected head dipping, Unprotected head dipping, Grooming, Rearing, Paw licking, Immobile sniffing

Effect of Tocotrienol on medium dose ethanol-induced alternations in serum superoxide and peroxide handling capacities (SPHC) in rat

729-734Tocotrienols are members of vitamin E family present in low concentrations and possess high antioxidant activity. Consumption of ethanol is a common problem and induces oxidative stress. In this study, we evaluated the effect of tocotrienol against ethanol-induced oxidative stress. Male albino Wistar rats were divided into two sets; one set of rats were exposed with low to moderate doses of ethanol for 4 weeks, while another set was exposed to tocotrienol orally (10 mg/day) in addition to the ‘low to moderate doses of ethanol for 4 weeks’. Oxidative stress parameters, like levels of reduced glutathione and lipid peroxidation, activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were determined in serum before the initiation of treatment protocol and at the end of 2nd and 4th week of treatment. Serum levels of superoxide and peroxide handling capacities were also calculated in those three time points. Tocotrienol-treated rats showed statistically significant enhancement in reduced glutathione level, glutathione peroxidase and glutathione reductase activities. Glutathione-dependent superoxide and peroxide handling capacity of those rats were found to be higher. The current study suggests that the tocotrienol-induced protection against the oxidative stress is most likely mediated by glutathione-based system

Correlation between regional oxidative stress markers of the cerebrum and spatial learning in tocotrienol-mediated protection against light-to-moderate doses of ethanol exposure

341-350Tocotrienol, a multipotent nutraceutical with antioxidative, anti-inflammatory and neuroprotective properties, could be used to maintain the cognitive functions even in the presence of neurotoxicants. Oral supplementation of two doses of tocotrienol was used during the three doses of ethanol exposure (comparable with low-to-moderate doses of alcohol consumption in human), and learning, retention, and utilisation of navigation performances were evaluated and correlated with the level of oxidative stress markers in cerebral regions. Rats received ethanol exposure for 4 weeks and tocotrienol supplementation for 4 weeks of ethanol exposure and continued for 2 more weeks. The significant decrement in weight gain during the experimentation was observed only in the groups receiving the highest amount of ethanol exposure (0.6 mg/kg body weight). Only the group exposed to ethanol at 0.4 mg/kg bw demonstrated alterations in acquisition time and post-48 h retention time of Morris water maze navigation task. Significant influences of ethanol exposure and tocotrienol supplementation were observed in the probe test using the Morris water maze. The correlation between oxidative stress parameters of cerebral regions and probe test did not provide any significant information; however, indicated that investigated domains of cognition most likely were associated with frontal cortex and temporal cortex functions

Thalamic superoxide and peroxide handling capacity (SPHC): An experimental study with aluminum, ethanol and tocopherol in rats

568-573Superoxide and peroxide handling capacity (SPHC) is an important determinant of oxidative stress. Neurotoxic impacts of aluminum are associated with oxidant imbalance. Here, we studied the influence of aluminum on oxidative stress parameters, antioxidative enzymes and SPHC of thalamic area on pro-oxidant (ethanol) and antioxidant (-tocopherol) exposure. Two sets of male Wistar rats were divided into 8 groups (6 each) and exposed to aluminum (10 mg/Kg body wt.), ethanol (0.6 g/Kg body wt.) and -tocopherol (5 IU/day) for 4 wk, each having respective control group. Levels of reduced glutathione (GSH), lipid peroxidation (TBARS) along with activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) of thalamic area were estimated for each group. Glutathione-independent superoxide peroxide handling capacity (GI-SPHC) and glutathione-dependent superoxide peroxide handling capacity (GD-SPHC) were calculated from the GPx, CAT and SOD values. Concomitant exposure to aluminum and ethanol demonstrated significant increase in SOD activity and significant decrease in GPx activity compared to the control group, while lone aluminum-exposed rats showed raised GR activity, without alterations in GPx and SOD activities. However, significant reduction of both GI- and GD- SPHC were found in ethanol-exposed groups. -Tocopherol supplementation could resist most of the alterations. In addition, current antioxidant exposure reduced the inherent GD-SPHC, and thus, made thalamic area more vulnerable to oxidant threat. The present study corroborates the thalamic susceptibility to aluminum-augmented oxidant imbalance and suggests cautious use of antioxidant supplementation against neurodegenerative disorders. </span

Influence of ethanol on aluminum-induced alterations in oxidative stress of rat thalamic area

Background: Neurotoxic impacts of aluminum are associated with oxidant imbalance and implicated in many senile neurodegenerative disorders. Thalamus is relatively protected from aging-related issues, however, seldom studied. Aims: The study is aimed to find out the aluminum-induced oxidative stress in thalamic area and the influence of ethanol on that. Settings and Design: Influence of aluminum on oxidative stress parameters in the thalamic area has been studied in the presence of varied levels of ethanol exposures. Materials and Methods: Male Wistar rats were exposed to aluminum (10 mg/kg bw) and ethanol (0.8-1.6 g/kg bw). Thalamic levels of reduced glutathione (GSH) and lipid peroxidation thiobarbituric acid reactive substances (TBARS) were studied, along with the activities of superoxide dismutase (SOD), catalase, glutathione peroxidise (GPx), and glutathione reductase (GR). Statistical Analysis Used: The data were statistically analyzed using Kruskal-Wallis test for variance and the significance of the difference between groups was studied using Mann-Whitney U test. Results: Lone aluminum exposure failed to produce any alterations in all the tested parameters, except the GPx activity of thalamic area. Nevertheless, concomitant ethanol exposure caused significant alterations in those thalamic parameters barring GSH level and SOD activity. Maximum response was observed with the highest dose of ethanol exposure. Conclusions: Though thalamic area is reported to be selectively susceptible to aluminum-induced oxidative stress, concomitant presence of pro-oxidant dominance might have augmented the aluminum-induced oxidative stress there. The observation may help to understand the mechanistic riddle of oxidative stress created by aluminum, a redox-inactive metal