Precision-cut liver slices in culture as a tool to assess the physiological involvement of Kupffer cells in hepatic metabolism

Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Département des Sciences Pharmaceutiques, Université Catholique de Louvain, PMNT-UCL 73 avenue Mounier, B-1200 Brussels, Belgium.
Comparative Hepatology (Impact Factor: 1.88). 02/2004; 3 Suppl 1:S45. DOI: 10.1186/1476-5926-2-S1-S45
Source: PubMed
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Available from: Nathalie Delzenne, Aug 06, 2015
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    • "In order to investigate the potential role of CoQ10 as an anti-inflammatory compound during acute sepsis, we have tested the potential modulation of acute hepatic inflammation induced in vitro in rat precision-cut liver slices (PCLS). The PCLS model was chosen because it allows to keep functional the different cell types-including immune liver cells-and respects the cellecell interactions occurring in the liver tissue in vivo [1] [3]. Moreover we have tested the role of Qx oral supplementation on hepatic LPS-induced inflammation in vivo in mice 1 h after the injection of 0.1 mg/kg body weight LPS. "
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    ABSTRACT: Sepsis is characterized by a systemic dysregulated inflammatory response and oxidative stress. A large body of evidence supports a key role of mitochondrial dysfunction during the various phases of sepsis (early and late-phase of sepsis-associated multiorgan failure). Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial and respiratory chain, and is depleted in septic shock patients. However its effect on acute sepsis remains unexplored. The reduced form of CoQ10 (Qx) has been shown to lessen pro-inflammatory response in macrophages or fibroblasts in culture. The aim of the study is to investigate the effect of Qx on hepatic inflammation in models of acute LPS-induced inflammation.
    Full-text · Article · Sep 2015
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    • "GdCl 3 , a specific inhibitor of Kupffer cells, is often used as tool for studying the role of Kupffer cells [11] [12] [13] [14] [15] [16]. Furthermore, we have previously demonstrated in vitro that inflammatory mediators released by the liver tissue (TNF-a, PGE 2 and nitrites) are decreased after GdCl 3 -treatment, independently of the presence of inflammatory stimulus [8]. In the present study, we demonstrate that the phagocytic and functionality of Kupffer cells are inhibited after administration of GdCl 3 without acting on resident macrophages in other organs, such as the spleen or the white adipose tissue , as previously described [11] [12] [14]. "
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    ABSTRACT: The aim of this study was to investigate the role of Kupffer cell in glucose metabolism and hepatic insulin sensitivity in mice. Both phagocytic activity and secretory capacity of Kupffer cells were blunted 24h after GdCl3 administration. Glucose tolerance--evaluated following an oral glucose tolerance test (OGTT)--was higher in GdCl3-treated mice whereas fasting insulinemia and HOMA-IR index decreased. The improvement of glucose tolerance and hepatic insulin signalling pathway after inhibition of Kupffer cells was supported by a lower hepatic gluconeogenic enzyme expression and a higher phosphorylation of Akt upon insulin challenge. Moreover, fasting hyperglycemia, insulin resistance and impaired glucose tolerance--induced by high fat (HF) diet--were improved through chronic administration of GdCl3. Interestingly, the inhibition of Kupffer cell exerted antiobesity effects in HF-fed mice, and lowered hepatic steatosis. Therefore, strategies targeting Kupffer cell functions could be a promising approach to counteract obesity and related metabolic disorders.
    Full-text · Article · Aug 2009 · Biochemical and Biophysical Research Communications
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    ABSTRACT: Influenced by the ancient literature of various communities and reports presented by modern authors regarding the medicinal uses of Colocacia esculenta., present study was conducted to investigate the antihepatotoxic efficacy associated with Colocacia esculenta whole leaf juice. The antihepatotoxic and hepatoprotective studies were carried against two well known hepaotoxins paracetamol and CCl 4 using in vitro liver slice method. The free radicals generated by CCl 4 and paracetamol cause oxidative stress as well as damage various cell organellaes consequently resulting in injury to the hepatocytes. The extent of damage caused by these free radicals as well as evaluation of antihepatotoxic and hepatoprotective efficacy associated with the Colocacia esculenta leaf juice was measured using the leakage of marker enzymes of liver function viz AST, ALT and ALP in the incubation medium. In presence of CCL 4 as well as paracetamol there was increase in the levels of marker enzymes indicating hepatotoxicity of these compounds. At one and two hours interval insignificant alterations were observed in the enzymes levels. Marked elevations of toxicity marker enzymes were noted at four hours in presence of CCl 4 as well as paracetamol. However the leaf juice of Colocacia esculenta remarkably declined the leakage of AST, ALT and ALP in the medium indicating hepatocyte integrity. The investigation is supportive to conclude that the Colocacia esculenta leaf juice as a whole possesses antihepatotoxic and hepatoprotective efficacy when tested in vitro using rat liver slice model.
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