PMID- 11906245
OWN - NLM
STAT- MEDLINE
DCOM- 20020425
LR  - 20161124
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 179
IP  - 3
DP  - 2002 Mar 15
TI  - Tumor necrosis factor-alpha-null mice are not resistant to cadmium 
      chloride-induced hepatotoxicity.
PG  - 155-62
AB  - Acute administration of cadmium results in hepatotoxicity. Recent reports 
      indicate that Kupffer cells, the resident macrophages of the liver, participate 
      in the manifestation of chemical-induced hepatotoxicity. Tumor necrosis 
      factor-alpha (TNF-alpha) is a proinflammatory cytokine that is a major product of 
      Kupffer cells and mediates the hepatotoxic effects of lipopolysaccharide (LPS). 
      It has been speculated that cadmium also may exert its hepatotoxicity via the 
      production of TNF-alpha by the Kupffer cells. Therefore, this study was 
      undertaken to determine whether mice deficient in TNF-alpha are resistant to 
      Cd-induced hepatotoxicity. TNF-alpha-null (TNF-KO) and wild-type (WT) mice were 
      dosed ip with saline, LPS (0.1 mg/kg)/Gln (d-galactosamine, 700 mg/kg), or CdCl2 
      (2.2, 2.8, 3.4, and 3.9 mg Cd/kg). Serum alanine aminotransferase (ALT) and 
      sorbitol dehydrogenase (SDH) activities were quantified to assess liver injury. 
      Caspase-3 activity was quantified to assess hepatocellular apoptosis. LPS/Gln 
      treatment increased ALT (17-fold) and SDH (21-fold) in WT mice. In contrast, 
      LPS/Gln-treatment did not significantly increase ALT or SDH in TNF-KO mice. 
      LPS/Gln-treatment caused a 7.8-fold increase in caspase-3 activity in WT mice but 
      did not increase caspase-3 in TNF-KO mice. Cadmium caused a dose-dependent 
      increase in liver injury in both WT and TNF-KO mice. However, the liver injury 
      produced by Cd in the TNF-KO mice was not different from that in WT at any dose. 
      No significant increase in caspase-3 activity was detected in any of the 
      Cd-treated mice. These data indicate that, in contrast to LPS/Gln-induced 
      hepatotoxicity, TNF-alpha does not appear to mediate Cd-induced hepatotoxicity.
CI  - Copyright 2002 Elsevier Science (USA).
FAU - Harstad, Eric B
AU  - Harstad EB
AD  - Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas 
      Medical Center, Kansas City, Kansas 66160, USA.
FAU - Klaassen, Curtis D
AU  - Klaassen CD
LA  - eng
GR  - ES-01142/ES/NIEHS NIH HHS/United States
GR  - ES-07079/ES/NIEHS 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 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 1.1.1.14 (L-Iditol 2-Dehydrogenase)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - J6K4F9V3BA (Cadmium Chloride)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cadmium Chloride/*toxicity
MH  - Caspase 3
MH  - Caspases/analysis
MH  - *Chemical and Drug Induced Liver Injury
MH  - Galactosamine/pharmacology
MH  - Histocytochemistry
MH  - L-Iditol 2-Dehydrogenase/blood
MH  - Lipopolysaccharides/pharmacology
MH  - Liver Diseases/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Tumor Necrosis Factor-alpha/deficiency/*physiology
EDAT- 2002/03/22 10:00
MHDA- 2002/04/26 10:01
CRDT- 2002/03/22 10:00
PHST- 2002/03/22 10:00 [pubmed]
PHST- 2002/04/26 10:01 [medline]
PHST- 2002/03/22 10:00 [entrez]
AID - S0041008X01993627 [pii]
AID - 10.1006/taap.2001.9362 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2002 Mar 15;179(3):155-62. doi: 10.1006/taap.2001.9362.