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Open Access Highly Accessed Research article

Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease

Judit Marsillach, Jordi Camps*, Natàlia Ferré, Raul Beltran, Anna Rull, Bharti Mackness, Michael Mackness and Jorge Joven

Author Affiliations

Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigacions Sanitàries Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Spain

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BMC Gastroenterology 2009, 9:3  doi:10.1186/1471-230X-9-3

Published: 14 January 2009

Abstract

Background

Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.

Methods

CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.

Results

High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARδ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).

Conclusion

Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.