Influence of age on arsenic-induced behavioral and cholinergic perturbations: Amelioration with zinc and α-tocopherol

Abstract

This study was planned to determine arsenic (As) (10 mg/kg body weight given through oral gavage) induced behavioral and cholinergic perturbations in three different age groups of rats; young (postnatal day 21), adult (3 months), and aged (18 months) at 7 days post-acute exposure ( n = 6 for each of the four groups of all three age points). Further, we also evaluated the ameliorative effect of essential metal zinc (Zn; 0.02% through drinking water) and an antioxidant, α-tocopherol (vitamin E; 125 mg/kg body weight through oral gavage) against As-induced neurotoxicity. As exposure showed significant alterations in behavioral functions (open-field behavior, total locomotor activity, grip strength, exploratory behavior, and water maze learning). Cholinergic studies in three brain regions (cerebral cortex, cerebellum, and hippocampus) of different age groups also showed significant increase in acetylcholine levels and a decrease in acetylcholinesterase activity. These effects were more pronounced in hippocampus followed by cerebral cortex and cerebellum. Among the three different age points, aged animals were found to be more vulnerable to the As-induced toxicity as compared to young and adult animals suggesting that As neurotoxicity is age dependent. These As-induced alterations were significantly reversed following supplementation with Zn or vitamin E. However, vitamin E was found to elicit greater protection as compared to Zn in restoring the altered behavioral and cholinergic perturbations, providing evidence for As-induced oxidative damage.