Arsenic-induced cell death in liver and brain of experimental rats.
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.
Bashir
Somia
S
Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences (AIIMS), New Delhi-29, India.
Sharma
Yukti
Y
Irshad
M
M
Gupta
S Dutta
SD
Dogra
T D
TD
D000818:Animals; D017209:Apoptosis; D018053:Arsenites / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009336:Necrosis; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D020169:Caspases; D005978:Glutathione