| 15686116 |
Su PH, Takehashi M, Tanaka S, Banasik M, Stedeford T, Ueda K, Muro-Cacho C, Harbison RD: Hepatocellular accumulation of poly (ADP-ribose) in male ICR mice treated with a necrogenic dose of carbon tetrachloride. Res Commun Mol Pathol Pharmacol. 2003;113-114:171-9.
Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) in response to oxidative stress has been shown to contribute to necrotic cell death by consuming NAD+ and ATP. In the present study, PARP-1 overactivation was determined by identifying the distribution and accumulation of poly (ADP-ribose) following intraperitoneal administration of a hepatotoxic dose of carbon tetrachloride (572 mg/kg). Treated animals exhibited lipid peroxide levels 16.5-fold higher than controls. Serum activities of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase were increased by 6.1-fold and 22.8-fold, respectively. Lactate dehydrogenase activity was significantly increased by 1.2-fold. Histopathological analyses revealed severe necrosis and increased poly (ADP-ribsyl) ation of cells in the centrilobular region of treated animals versus saline controls. These results demonstrate the role of PARP-1 overactivation in chemical-induced pathologies and suggest the potential role of PARP-1 inhibitors at preventing toxicity. |
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