Arsenic induced apoptosis in rat liver following repeated 60 days exposure.
BACKGROUND
Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 microM) concentration.


OBJECTIVE
The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver.


METHODS
Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis.


RESULTS
A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern.


CONCLUSIONS
Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis.
Bashir
Somia
S
Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India. somia24bashir@rediffmail.com
Sharma
Yukti
Y
Irshad
M
M
Nag
T C
TC
Tiwari
Monica
M
Kabra
M
M
Dogra
T D
TD
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009336:Necrosis / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases