title: Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Dipartimento di Medicina e Oncologia Sperimentale, University of Turin, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zamara
authors.forename: Sara
authors.initials: S
authors.lastname: Galastri
authors.forename: Sara
authors.initials: S
authors.lastname: Aleffi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Petrai
authors.forename: Manuela
authors.initials: M
authors.lastname: Aragno
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mastrocola
authors.forename: Erica
authors.initials: E
authors.lastname: Novo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bertolani
authors.forename: Stefano
authors.initials: S
authors.lastname: Milani
authors.forename: Francesco
authors.initials: F
authors.lastname: Vizzutti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Giorgio
authors.initials: G
authors.lastname: LaVilla
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
mesh_terms: D000447:Aldehydes / Q000032:analysis; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism
chemical_list: D000447:Aldehydes; D018932:Chemokine CCL2; D016207:Cytokines; D017382:Reactive Oxygen Species; D002251:Carbon Tetrachloride; C027576:4-hydroxy-2-nonenal