PMID- 10378475
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 133
IP  - 2-3
DP  - 1999 Apr 15
TI  - Impairment of TNF-alpha expression and secretion in primary rat liver cell 
      cultures by acetaminophen treatment.
PG  - 85-92
AB  - Tumor necrosis factor-alpha (TNF-alpha) is assumed to act as a mediator in toxic 
      liver injury, aggravating the primary damage to the parenchymal liver cell, but 
      also stimulating liver regeneration. Reports on the effect of acetaminophen in 
      vivo on TNF-alpha transcript concentrations and serum TNF-alpha concentrations, 
      under different experimental, or clinical conditions have yielded controversial 
      results. We used primary rat hepatocyte and Kupffer cell cultures to test the 
      direct action of subtoxic and toxic concentrations of acetaminophen on TNF-alpha 
      expression and release. We observed a dose-dependent decrease of TNF-alpha mRNA 
      in the hepatocytes, and of TNF-alpha release into the medium of hepatocyte 
      cultures. The data also indicate an impairment of TNF-alpha release in Kupffer 
      cell cultures after treatment with nontoxic, as well as with toxic, acetaminophen 
      concentrations. The results suggest that inhibition of TNF-alpha expression and 
      release in the liver is a consequence of acetaminophen exposure. It is at present 
      unknown how this effect modulates the course of acetaminophen intoxication.
FAU - Nastevska, C
AU  - Nastevska C
AD  - Institute of Toxicology, University of Dusseldorf, Germany.
FAU - Gerber, E
AU  - Gerber E
FAU - Horbach, M
AU  - Horbach M
FAU - Rohrdanz, E
AU  - Rohrdanz E
FAU - Kahl, R
AU  - Kahl R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 362O9ITL9D (Acetaminophen)
SB  - IM
MH  - Acetaminophen/*toxicity
MH  - Analgesics, Non-Narcotic/*toxicity
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Kupffer Cells/cytology/drug effects/metabolism
MH  - Liver/cytology/*drug effects/*metabolism
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/*metabolism
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
AID - S0300-483X(99)00007-4 [pii]
AID - 10.1016/s0300-483x(99)00007-4 [doi]
PST - ppublish
SO  - Toxicology. 1999 Apr 15;133(2-3):85-92. doi: 10.1016/s0300-483x(99)00007-4.