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.
ABSTRACT
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.