Arsenic is a well established human
carcinogen and is ubiquitous in the environment. The present study demonstrates the effect of acute
arsenic administration at three different doses in liver and brain of Wistar rats.
Sodium arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg of
body weight on the basis of a lethal dose 50% (LD50) for 24 hr. After administration of
arsenites, liver and brain were analyzed for various parameters of oxidative stress, histopathological changes and
caspase-3 activity.
Glutathione levels were decreased significantly in the liver at all doses. In liver the following biochemical changes were observed, a significant lipid peroxidation and cytochrome-P450 induction along with significant decrease in
catalase and
superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of
glutathione peroxidase was increased significantly at all doses. In brain, no significant change was observed at 6.3 mg/kg. However, a significant increase in lipid peroxidation and
glutathione peroxidase activity along with significant decrease in the activity of
glutathione,
catalase and
superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of
glutathione-S-transferase was decreased significantly in both liver and brain at 10.5 and 12.6 mg/kg. No significant alteration in the activity of
glucose-6-phosphate dehydrogenase and
glutathione reductase was observed in either liver or brain at any dose. Dose-dependent histopathological changes, observed in both liver and brain are also described. A significant increase in
caspase-3 activity was observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain.
Sodium arsenite caused DNA cleavage into fragments and manifested as "
DNA laddering", a hallmark of apoptosis.