ABSTRACT
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.
ABSTRACT
Neurotoxic role of aluminum is being implicated in the neurodegenerative changes and neurobehavioral pathology. Prooxidant (ethanol) exposures were found to augment the neurochemical alterations in different brain regions. Current study was aimed to follow up aluminum-induced alterations in open-field behavior of rats in absence and presence of varied doses of ethanol (prooxidant) exposure for four weeks. Male Wistar rats were exposed to oral aluminum chloride gavage (Al+ animals; 10 mg/Kg bw) and concomitantly treated with ethanol (0.2, 0.4 and 0.6 g/Kg bw) daily. Open-field behavior of rats were recorded weekly and processed for ambulatory, thigmotaxic and spatial behaviors; and compared with controls – Al0 (without aluminum exposure) and Et-0 (without ethanol exposure). Lone aluminum exposure was found to alter the quadrant preferences only at the end of 4th week of treatment. However, differences in quadrant preferences between Al0 and Al+ animals were observed at the end of 1st week itself in presence of prooxidant exposures. Significant influences of aluminum was seldom during the initial weeks and were restricted to right angle turn and wall climbing behaviors, while many parameters were significantly influenced by ethanol exposures at the end of third week. By the end of 4th week, ambulation, thigmotaxis and quadrant preferences were found to be significantly influenced by either aluminum or ethanol exposures and/or their interactions. The study clearly indicates that certain aspect of neurobehavioral toxicity of aluminum can be aggravated by concomitant presence of prooxidant dominance. Present investigation accentuates the role of aluminum toxicity in behavioral neuropathology and revealed that there are at least two specific mechanisms of aluminum-induced neurobehavioral alterations – one is oxidative stress dependent while the other is not.