Memory dysfunction and Oxidative DNA damage in rat treated by Arsenic

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

1Faculty 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 stress-

induced 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.