Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ACETAMINOPHEN HEPATOTOXICITY IN TUMOR NECROSIS FACTOR-LYMPHOTOXIN-ALPHA GENE KNOCKOUT MICE
Autore:
BOESS F; BOPST M; ALTHAUS R; POLSKY S; COHEN SD; EUGSTER HP; BOELSTERLI UA;
Indirizzi:
ETH ZURICH,INST TOXICOL,SWISS FED INST TECHNOL,SCHORENSTR 16 CH-8603 SCHWERZENBACH SWITZERLAND ETH ZURICH,INST TOXICOL,SWISS FED INST TECHNOL CH-8603 SCHWERZENBACH SWITZERLAND UNIV ZURICH CH-8603 SCHWERZENBACH SWITZERLAND UNIV CONNECTICUT,DEPT PHARMACEUT SCI,TOXICOL PROGRAM STORRS CT 00000
Titolo Testata:
Hepatology
fascicolo: 4, volume: 27, anno: 1998,
pagine: 1021 - 1029
SICI:
0270-9139(1998)27:4<1021:AHITNF>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED HEPATIC NECROSIS; BINDING LIVER PROTEINS; COVALENT BINDING; MOUSE-LIVER; IN-VIVO; IMMUNOCHEMICAL DETECTION; ACTIVATED MACROPHAGES; DRUG-METABOLISM; POTENTIAL ROLE; CELL-LYSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
F. Boess et al., "ACETAMINOPHEN HEPATOTOXICITY IN TUMOR NECROSIS FACTOR-LYMPHOTOXIN-ALPHA GENE KNOCKOUT MICE", Hepatology, 27(4), 1998, pp. 1021-1029

Abstract

Recent evidence suggests that macrophages and/or other nonparenchymalcells may release important mediators contributing to the hepatic necrosis induced by high doses of acetaminophen (APAP), The nature and causative role of these mediators has remained elusive, however, To investigate the role of the proinflammatory cytokine, tumor necrosis factor (TNF) in the initiation and early propagation of APAP-induced liver injury we have used mice deficient in both TNF and the closely relatedlymphotoxin-alpha (LT-alpha), Male TNF/LT-alpha knockout mice and C57BL/6 wild-type mice were treated with a hepatotoxic dose of APAP (400 mg/kg, intraperitoneally), and the development of liver injury was monitored over 8 hours, Both genotypes exhibited similar basal activitiesof hepatic cytochrome P450 2E1 and 1A2, After APAP administration, both the rate of glutathione consumption and the extent of subsequent selective protein binding did not differ significantly in the knockout and wild-type mice, The TNF/LT-alpha-deficient mice developed severe centrilobular necrosis and exhibited highly increased levels of serum alanine aminotransferase and aspartate aminotransferase, the extent of which was not significantly different from that in wild-type mice, In C57BL/6 mice exposed to APAP, no increases in hepatic transcripts of TNF or LT-alpha were found by reverse transcription-polymerase chain reaction, nor was immunoreactive serum TNF detected by enzyme-linked immunosorbent assay over 8 hours posttreatment. These data indicate that, in the absence of the genes encoding for TNF and LT-alpha, APAP bioactivation was not altered and mice still developed severe hepatic necrosis, Thus, TNF is unlikely to be a key mediator in the early pathogenesis of APAP-induced hepatotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/21 alle ore 02:44:05