PMID- 14550746
OWN - NLM
STAT- MEDLINE
DCOM- 20031124
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 192
IP  - 2
DP  - 2003 Oct 15
TI  - Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor 
      receptor-1. Potential role of inflammatory mediators.
PG  - 119-30
AB  - Transgenic mice with a targeted disruption of the tumor necrosis factor receptor 
      1 (TNFR1) gene were used to analyze the role of TNF-alpha in pro- and 
      anti-inflammatory mediator production and liver injury induced by acetaminophen. 
      Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in 
      centrilobular hepatic necrosis. This was correlated with expression of inducible 
      nitric oxide synthase (NOS II) and nitrotyrosine staining of the liver. 
      Expression of macrophage chemotactic protein-1 (MCP-1), KC/gro, interleukin-1beta 
      (IL-1beta), matrix metalloproteinase-9 (MMP-9), and connective tissue growth 
      factor (CTGF), inflammatory mediators known to participate in tissue repair, as 
      well as the anti-inflammatory cytokine, interleukin-10 (IL-10), also increased in 
      the liver following acetaminophen administration. TNFR1(-/-) mice were found to 
      be significantly more sensitive to the hepatotoxic effects of acetaminophen than 
      wild-type mice. This was correlated with more rapid and prolonged induction of 
      NOS II in the liver and changes in the pattern of nitrotyrosine staining. 
      Acetaminophen-induced expression of MCP-1, IL-1beta, CTGF, and MMP-9 mRNA was 
      also delayed or reduced in TNFR1(-/-) mice relative to wild-type mice. In 
      contrast, increases in IL-10 were more rapid and more pronounced. These data 
      demonstrate that signaling through TNFR1 is important in inflammatory mediator 
      production and toxicity induced by acetaminophen.
FAU - Gardner, Carol R
AU  - Gardner CR
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University and 
      University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical 
      School, Piscataway, NJ 08854-8020, USA.
FAU - Laskin, Jeffrey D
AU  - Laskin JD
FAU - Dambach, Donna M
AU  - Dambach DM
FAU - Chiu, Hawjyh
AU  - Chiu H
FAU - Durham, Stephen K
AU  - Durham SK
FAU - Zhou, Peihong
AU  - Zhou P
FAU - Bruno, Mary
AU  - Bruno M
FAU - Gerecke, Donald R
AU  - Gerecke DR
FAU - Gordon, Marion K
AU  - Gordon MK
FAU - Laskin, Debra L
AU  - Laskin DL
LA  - eng
GR  - ES04738/ES/NIEHS NIH HHS/United States
GR  - ES05022/ES/NIEHS NIH HHS/United States
GR  - ES06897/ES/NIEHS NIH HHS/United States
GR  - EY09056/EY/NEI NIH HHS/United States
GR  - GM34310/GM/NIGMS NIH HHS/United States
GR  - HL677708/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 362O9ITL9D (Acetaminophen)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Acetaminophen/*toxicity
MH  - Analgesics, Non-Narcotic/*toxicity
MH  - Animals
MH  - Antigens, CD/*genetics/physiology
MH  - Blotting, Western
MH  - *Chemical and Drug Induced Liver Injury/enzymology/metabolism
MH  - Cytokines/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Induction
MH  - Injections, Intraperitoneal
MH  - *Liver/drug effects/enzymology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nitric Oxide Synthase/biosynthesis
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger/analysis
MH  - Receptors, Tumor Necrosis Factor/*genetics/physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction/physiology
MH  - Time Factors
EDAT- 2003/10/11 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/10/11 05:00
PHST- 2003/10/11 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/10/11 05:00 [entrez]
AID - S0041008X03002734 [pii]
AID - 10.1016/s0041-008x(03)00273-4 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2003 Oct 15;192(2):119-30. doi: 
      10.1016/s0041-008x(03)00273-4.