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Memory dysfunction and Oxidative DNA damage in rat treated by Arsenic

Muhammad Shahdaat Bin Sayeed1, Faizule Hasan2, Mohammad Arif2, Abul Hasnat3

Faculty of pharmacy, 2Department of Biochemistry and molecular biology , 3Department of

Clinical Pharmacy and Pharmacology; University of Dhaka, Dhaka-1000, Bangladesh.

ABSTRACT: Recent studies have pointed out that Arsenic trioxide is associated with the formation of reactive oxygen species, injury/damage to the nervous system and behavioral abnormalities. However, the causal relationship between Reactive Oxygen Species (ROS) and neuronal DNA damage and their synergistic role in the pathogenesis of Arsenic trioxide are obscure. Therefore, in the present study we examined the dose dependent effect of Arsenic Trioxide (0, 25, 50, 100 mg/kg body weight) on oxidative stress and oxidative DNA damage in rat brain regions. We further measured the spatial memory performance by T-maze following five days consecutive treatment with Arsenic. Arsenic exposure dose-dependently increased the level of lipid peroxidation, protein carbonyl, 2-deoxyrobose degradation and glutathione peroxidase along with a down regulated level of superoxide dismutase only in the hippocampus at the doses of 50 and 100 mg/kg. No significant change was observed in other brain regions in any doses tested. A significant increase in mean comet tail length was observed at both 50 and 100 mg/kg doses in the hippocampus as compared with controls. Furthermore, treatment with Arsenic at does of 50 and 100 mg/kg impaired the working memory as measured by T-maze. In conclusion, the present study gives an indication of an association between oxidative stressinduced DNA damage and cognitive decline in animal model of Arsenic poisoning.

Alumnus, IBRO-APRC School of neuroscience: Bioimaging, Behavior and Functional Genomics: BRIMS, Monash University Sunway Campus, Malaysia, 4-14 October 2010. Country of Residence: Bangladesh.