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
Download full-text


Available from: Nathalie Delzenne, Aug 06, 2015
7 Reads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Biochemical and Biophysical Research Communications 08/2009; 385(3):351-6. DOI:10.1016/j.bbrc.2009.05.070 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we tested the hypothesis that dietary oligofructose (FOS) can modulate both the response to an endotoxic shock induced by lipopolysaccharide (LPS) administration and the activity of resident hepatic macrophages, i.e., Kupffer cells. Male Wistar rats (n = 5-9 per group) were fed a standard diet or a diet supplemented with 10 g/100 g FOS for 3 wk. LPS (10 mg/kg) or saline were injected i.p. after dietary treatment. After LPS injection, serum levels of tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, and prostaglandin E(2) (PGE(2)), an immunosuppressive mediator, were higher in FOS-treated rats than in control rats. Alanine aminotransferase (ALT) activity was approximately 50% lower than in controls 24 h after LPS administration in FOS-treated rats, suggesting less hepatic injury; this was confirmed through histological analysis. FOS treatment increased the number of large phagocytic Kupffer cells, as assessed by histological examination of the liver after colloidal carbon injection into the portal vein. Precision-cut liver slices (PCLS) from FOS-treated rats released more TNF-alpha and PGE(2) into the incubation medium than PCLS from control rats, independently of LPS challenge in vitro. This would suggest that the higher Kupffer cell phagocytic activity and secretion capacity due to FOS supplementation improve LPS clearance in liver tissue and reduce hepatocyte alterations. This study supports the hypothesis that oligofructose might decrease liver tissue injury after endotoxic shock and sepsis.
    Journal of Nutrition 06/2004; 134(5):1124-9. · 3.88 Impact Factor
Show more