Abstract 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.

Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice / ZAMARA E; GALASTRI S; ALEFFI S; PETRAI I; ARAGNO M; MASTROCOLA R; NOVO E; BERTOLANI C; MILANI S; VIZZUTTI F; VERCELLI A; M. PINZANI; LAFFI G; LAVILLA G; PAROLA M; MARRA F. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - STAMPA. - 46:(2007), pp. 230-238.

Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice

GALASTRI, SARA;ALEFFI, SARA;PETRAI, ILARIA;BERTOLANI, CRISTIANA;MILANI, STEFANO;VIZZUTTI, FRANCESCO;PINZANI, MASSIMO;LAFFI, GIACOMO;LA VILLA, GIORGIO;MARRA, FABIO
2007

Abstract

Abstract 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.
2007
46
230
238
ZAMARA E; GALASTRI S; ALEFFI S; PETRAI I; ARAGNO M; MASTROCOLA R; NOVO E; BERTOLANI C; MILANI S; VIZZUTTI F; VERCELLI A; M. PINZANI; LAFFI G; LAVILLA G; PAROLA M; MARRA F
File in questo prodotto:
File Dimensione Formato  
laffi 3.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 850.57 kB
Formato Adobe PDF
850.57 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/255245
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact