PMID- 17125873
OWN - NLM
STAT- MEDLINE
DCOM- 20070316
LR  - 20161124
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 46
IP  - 2
DP  - 2007 Feb
TI  - Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient 
      mice.
PG  - 230-8
AB  - BACKGROUND/AIMS: Administration of carbon tetrachloride determines liver injury, 
      inflammation and oxidative stress, but the molecular mechanisms of damage are 
      only partially understood. In this study, we investigated the development of 
      acute toxic damage in mice lacking monocyte chemoattractant protein-1 (MCP-1), a 
      chemokine which recruits monocytes and activated lymphocytes. METHODS: Mice with 
      targeted deletion of the MCP-1 gene and wild type controls were administered a 
      single intragastric dose of carbon tetrachloride. Serum liver enzymes, histology, 
      expression of different chemokines and cytokines, and intrahepatic levels of 
      oxidative stress-related products were evaluated. RESULTS: Compared to wild type 
      mice, peak aminotransferase levels were significantly lower in MCP-1-deficient 
      animals. This was paralleled by a delayed appearance of necrosis at histology. In 
      addition, MCP-1-deficient mice showed a shift in the pattern of infiltrating 
      inflammatory cells, with a predominance of polymorphonuclear leukocytes. Lack of 
      MCP-1 was also accompanied by reduced intrahepatic expression of cytokines 
      regulating inflammation and tissue repair. The increase in tissue levels of 
      reactive oxygen species and 4-hydroxy-nonenal following administration of the 
      hepatotoxin was also significantly lower in animals lacking MCP-1. CONCLUSIONS: 
      Lack of MCP-1 affords protection from damage and development of oxidative stress 
      in a toxic model of severe acute liver injury.
FAU - Zamara, Elena
AU  - Zamara E
AD  - Dipartimento di Medicina e Oncologia Sperimentale, University of Turin, Italy.
FAU - Galastri, Sara
AU  - Galastri S
FAU - Aleffi, Sara
AU  - Aleffi S
FAU - Petrai, Ilaria
AU  - Petrai I
FAU - Aragno, Manuela
AU  - Aragno M
FAU - Mastrocola, Raffaella
AU  - Mastrocola R
FAU - Novo, Erica
AU  - Novo E
FAU - Bertolani, Cristiana
AU  - Bertolani C
FAU - Milani, Stefano
AU  - Milani S
FAU - Vizzutti, Francesco
AU  - Vizzutti F
FAU - Vercelli, Alessandro
AU  - Vercelli A
FAU - Pinzani, Massimo
AU  - Pinzani M
FAU - Laffi, Giacomo
AU  - Laffi G
FAU - LaVilla, Giorgio
AU  - LaVilla G
FAU - Parola, Maurizio
AU  - Parola M
FAU - Marra, Fabio
AU  - Marra F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061023
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Aldehydes)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Reactive Oxygen Species)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aldehydes/analysis
MH  - Animals
MH  - Carbon Tetrachloride/toxicity
MH  - Chemical and Drug Induced Liver Injury/*genetics/*immunology/prevention & control
MH  - Chemokine CCL2/*genetics
MH  - Cytokines/genetics/metabolism
MH  - Gene Deletion
MH  - Liver/drug effects/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Neutrophils
MH  - Oxidative Stress/*genetics
MH  - Reactive Oxygen Species/analysis/metabolism
EDAT- 2006/11/28 09:00
MHDA- 2007/03/17 09:00
CRDT- 2006/11/28 09:00
PHST- 2006/04/10 00:00 [received]
PHST- 2006/09/16 00:00 [revised]
PHST- 2006/09/17 00:00 [accepted]
PHST- 2006/11/28 09:00 [pubmed]
PHST- 2007/03/17 09:00 [medline]
PHST- 2006/11/28 09:00 [entrez]
AID - S0168-8278(06)00553-8 [pii]
AID - 10.1016/j.jhep.2006.09.007 [doi]
PST - ppublish
SO  - J Hepatol. 2007 Feb;46(2):230-8. doi: 10.1016/j.jhep.2006.09.007. Epub 2006 Oct 
      23.