title: Hepatocellular accumulation of poly(ADP-ribose) in male ICR mice treated with a necrogenic dose of carbon tetrachloride.
abstract: 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.
authors.affiliation: Center for Environmental and Occupational Risk Analysis and Management, Department of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa, Florida 33612, USA.
authors.forename: Phi-Huynh
authors.initials: PH
authors.lastname: Su
authors.forename: Masanori
authors.initials: M
authors.lastname: Takehashi
authors.forename: Seigo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Marek
authors.initials: M
authors.lastname: Banasik
authors.forename: Todd
authors.initials: T
authors.lastname: Stedeford
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ueda
authors.forename: Carlos
authors.initials: C
authors.lastname: Muro-Cacho
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Harbison
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D008315:Malondialdehyde; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases