title: Cadmium-induced apoptosis of hepatocytes is not associated with death receptor-related caspase-dependent pathways in the rat.
abstract: Cadmium (Cd) is a heavy metal of considerable environmental and occupational concern. The liver is the major target organ of Cd toxicity that follows from repeated exposure to Cd. The aim of this study was to investigate the mechanism of cell death of Cd-induced hepatotoxicity in a rat model. Eighteen adult male Sprague-Dawley (SD) rats were injected daily with a dose of Cd acetate (30μM/kg body weight, subcutaneously). After 1, 2 and 7 days rats were euthanized and blood and liver tissues were sampled for analysis. Biochemical analyses of the level of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were undertaken. Histopathological and Western blot analyses for liver cellular damage and cell death were also performed. The results for the Cd-treated group of animals were compared to those from 12 control rats. The serum AST/ALT levels increased significantly 24h after CD exposure. From the Western blot analyses, activation of Bid, independent of caspase-8 was seen and Bax induced the release of cytochrome c into the cytosol from mitochondria in a dose-dependent manner. The level of Bcl-2 was decreased. Eventually, caspase-9 and caspase-3 were activated, and poly(ADP-ribose) polymerase (PARP) was cleaved in a dose-dependent manner. A histopathological analysis and DNA fragmentation test showed apoptotic cell death of the hepatocytes increased over time. These results suggest that Cd-induced liver cell apoptosis in the rat, over a period of 7 days, may not be related to the death-receptor pathway. Moreover, apoptosis is dose-dependent and associated with the decrement of Bcl-2.
authors.affiliation: Department of Pathology, College of Medicine, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Lim