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

Tocotrienol, 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.

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

Tocotrienols 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.

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

Superoxide 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.

Aluminum and ethanol induce alterations in superoxide and peroxide handling capacity (SPHC) in frontal and temporal cortex.

Aluminum is an omnipresent neurotoxicant and has been associated with several neuropathological disorders. Cerebrum and cerebellum have been shown to face augmented oxidative stress when animals are exposed to aluminum and high doses of ethanol. To establish the link between oxidative stress and neurobehavioral alterations, the present study was conducted to determine the extent of oxidative stress in low levels of pro-oxidant (ethanol exposure) status of the functionally discrete regions of the cerebrum. Male Wistar rats were exposed to aluminum (10 mg/kg body wt) and ethanol (0.2-0.6 g/kg body wt) for 4 weeks. Spontaneous motor activity (SMA) and Rota-Rod performances (RRP) were recorded weekly during the period of exposure. At the end of 4th week, oxidative stress parameters were determined from the homogenized cerebral tissue. GSH-independent superoxide peroxide handling capacity (GI-SPHC) and GSH-dependent superoxide peroxide handling capacity (GD-SPHC) were determined for FC and TC upon exposure to ethanol in the absence and presence of aluminum exposure. Aluminum was found to augment the oxidative stress at higher doses (0.6 g Ethanol/kg body wt) of ethanol, particularly in FC. The SPHC of FC was also found to be compromised significantly in aluminum-ethanol co-exposed animals. It was concluded that even though the manifestation of oxidative stress was not observed as revealed by assaying the widely used oxidative stress biochemical markers (indices), aluminum and ethanol (low doses) exposure induced alterations in the handling capacity of oxidant imbalance that could be recognized by studying the SPHC of FC. Comparison of GD-SPHC and GI-SPHC offered a possible mechanism of compromised SPHC in FC. This observation is likely to offer insights into the mechanism of association between aluminium exposure and behavioral changes in neurodegenerative disorders towards therapeutic strategies for these disorders.

Effect of aluminum exposure on superoxide and peroxide handling capacities by liver, kidney, testis and temporal cortex in rat.

Oxidant imbalance is one of the causative mechanisms of aluminum-induced neurotoxicity. In this study, we investigated aluminum-induced oxidant imbalance in non-neuronal tissues (liver, kidney and testis) and temporal cortex in rats. The differences in adaptations to superoxide and peroxide handling capacities (SPHC) of studied organs due to aluminum insult were also evaluated. Male Wistar rats were exposed to aluminum (10 mg/Kg body wt/day) for 4 weeks through orogastric intubation. Liver showed significant decrease in reduced glutathione level, while significant alteration in lipid peroxidation was observed in temporal cortex in aluminium-exposed animals. Superoxide dismutase activity was significantly altered in liver and temporal cortex and catalase activity significantly reduced in the liver due to aluminum exposure, while glutathione reductase and glutathione peroxidase activities were altered in all the tested organs. Among the organs, glutathione-independent SPHC was relatively higher in liver and kidney, while glutathione-dependent SPHC was relatively higher in testis and temporal cortex. As compared to control, aluminum-exposed rats demonstrated reduction in glutathione-dependent SPHC in temporal cortex and increment of the same in testis, while increment in glutathione-independent SPHC was observed in liver. In conclusion, aluminum-induced alteration in oxidant handling capacity could be the cause of oxidative stress both in the neuronal and non-neuronal tissues.