Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-alpha gene knockout mice

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
F BoessUrs A Boelsterli

Abstract

Recent evidence suggests that macrophages and/or other nonparenchymal cells 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 related lymphotoxin-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 activities of 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-ty...Continue Reading

References

Sep 1, 1992·Toxicology and Applied Pharmacology·L B SchookM J Myers
Feb 14, 1992·Biochemical and Biophysical Research Communications·N R PumfordJ A Hinson
Jan 1, 1992·Drug Metabolism Reviews·N P VermeulenR Van de Straat
Sep 11, 1990·European Journal of Biochemistry·K Decker
Nov 1, 1990·Seminars in Liver Disease·S D Nelson
Jun 15, 1987·Life Sciences·S I ShedlofskyC J McClain
Apr 14, 1986·Biochemical and Biophysical Research Communications·P GhezziM Bianchi
Apr 15, 1987·Biochemical Pharmacology·J B BartoloneE A Khairallah
Apr 1, 1995·Toxicology and Applied Pharmacology·F KayamaM I Luster
Oct 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J Muntané-RelatP Maurel
Oct 1, 1995·Toxicology and Applied Pharmacology·S J BuleraE A Khairallah
Jul 1, 1995·Toxicology and Applied Pharmacology·M E BlazkaM I Luster
Jan 1, 1995·Drug Metabolism Reviews·J A HinsonD W Roberts
Jan 1, 1995·Scandinavian Journal of Gastroenterology·I SakaidaK Okita
Apr 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D L LaskinD J Jollow
Dec 1, 1994·Toxicology and Applied Pharmacology·J E ManautouS D Cohen
Jun 9, 1993·Biochemical Pharmacology·G M Adamson, A W Harman
May 17, 1996·The Journal of Biological Chemistry·S S LeeF J Gonzalez
Feb 1, 1996·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J E ManautouS D Cohen
Sep 1, 1996·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·T A MacridesP F Wright
Jul 1, 1996·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·D J HoivikS D Cohen
Aug 1, 1996·The Journal of Pathology·R D GoldinS N Wickramasinghe
Jan 1, 1996·International Journal of Clinical & Laboratory Research·H J Gruss
Mar 1, 1997·Toxicology and Applied Pharmacology·S D CohenJ A Hinson
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·M W MarinoL J Old
Oct 1, 1995·Trends in Cell Biology·P VandenabeeleW Fiers

❮ Previous
Next ❯

Citations

Jul 1, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S L MichaelJ A Hinson
Jan 28, 2005·Journal of Biochemical and Molecular Toxicology·Helieh S OzTheresa S Chen
Aug 10, 2010·European Journal of Clinical Pharmacology·Hugh G LavertyB Kevin Park
Sep 12, 2000·Current Gastroenterology Reports·C J McClainS Shedlofsky
Jun 8, 2002·Biochemical and Biophysical Research Communications·Mohammed BourdiLance R Pohl
Mar 30, 1999·European Journal of Pharmacology·N MilosevicP Maier
Mar 30, 2005·Journal of Pediatric Gastroenterology and Nutrition·Judith A O'Connor, Sean Bennett
Jan 18, 2012·Critical Care : the Official Journal of the Critical Care Forum·Runkuan YangJyrki Tenhunen
Feb 5, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mohammed BourdiLance R Pohl
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hidenari NagaiNeil Kaplowitz
Apr 1, 2008·Digestive Diseases and Sciences·Helieh S Oz, Theresa S Chen
Mar 19, 2013·Immunopharmacology and Immunotoxicology·Irmak FerahElif Cadirci
Jul 25, 2006·Expert Opinion on Drug Metabolism & Toxicology·Zhang-Xu Liu, Neil Kaplowitz
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Hartmut Jaeschke
Jun 17, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lily DaraNeil Kaplowitz
Apr 7, 2000·The American Journal of Pathology·C M HogaboamS L Kunkel
Nov 13, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mitchell R McGillHartmut Jaeschke
Sep 20, 2008·Journal of Hepatology·Charalambos Gustav AntoniadesDiego Vergani
Aug 29, 2007·Clinics in Liver Disease·Basuki K Gunawan, Neil Kaplowitz
Oct 15, 2003·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Yoshiya ItoRobert S McCuskey
Mar 17, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Calivarathan LatchoumycandaneUrs A Boelsterli
Jul 13, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Hartmut JaeschkeMary L Bajt
Jun 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anup RamachandranHartmut Jaeschke
Nov 19, 2008·Chemico-biological Interactions·Yasuhiro MasubuchiToshiharu Horie
Mar 10, 2001·Clinics in Liver Disease·N Kaplowitz
Aug 21, 2012·Toxicology and Applied Pharmacology·Shubhra ChaudhuriLaura P James
Oct 3, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Kahkashan RashidParames C Sil
Oct 11, 2012·Journal of Hepatology·Junfeng AnStefan Donath
Feb 5, 2013·The American Journal of Pathology·Patrick ScheiermannHeiko Mühl
Mar 22, 2002·Toxicology and Applied Pharmacology·Eric B Harstad, Curtis D Klaassen
Mar 19, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Wei ZhengChang Liu
Oct 15, 2003·Journal of Leukocyte Biology·Yuko IshidaNaofumi Mukaida
Nov 5, 2017·Biochemical Society Transactions·Bernd Gesslbauer, Valery Bochkov
Jun 16, 2017·Gene Regulation and Systems Biology·Lisl Km ShodaBrett A Howell
Jan 28, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Herbert C YoheJacqueline F Sinclair
Jun 13, 2012·The Journal of Toxicological Sciences·Shingo ArakawaYasushi Yamazoe

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.