Modulation of paracetamol metabolism by Kupffer cells: A study on rat liver slices

Citation
A. Neyrinck et al., Modulation of paracetamol metabolism by Kupffer cells: A study on rat liver slices, LIFE SCI, 65(26), 1999, pp. 2851-2859
Citations number
35
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
00243205 → ACNP
Volume
65
Issue
26
Year of publication
1999
Pages
2851 - 2859
Database
ISI
SICI code
0024-3205(19991119)65:26<2851:MOPMBK>2.0.ZU;2-F
Abstract
Recent studies support the hypothesis that non parenchymal cells (mainly ma crophages) may play a role in the metabolism and cellular effects of parace tamol. In order to investigate this hypothesis, male Wistar rats were intra venously injected with either 7.5 mg/kg gadolinium chloride (Gd+) or NaCl 0 .9% (Gd-). The treatment with GdCl3 decreased the number and the function o f Kupffer cells in liver tissue, as assessed by the histological examinatio n of the liver after colloidal carbon injection in the portal vein. Precisi on-cut liver slices (PCLS) were prepared from both groups of rats and cultu red for 8h in Waymouth's medium in the presence and absence of 5 mM paracet amol. Interestingly, PCLS obtained from Gd+ rats exhibited a lower release of tumor necrosis factor (TNF-alpha) and a better viability than PCLS from control (Gd-) rats. Incubation with paracetamol led to a decreased glycogen level in liver slices from Gd+ or Gd-, without modifying neither liver mor phology nor ATP level nor LDH release. A higher proportion of paracetamol g lucuronide, was secreted from the slices obtained from Gd+ rats. These data suggest that Kupffer cells could affect the viability of PCLS in culture a nd are involved in the regulation of phase II metabolism in the adjacent he patocytes. We propose that PCLS in culture is a suitable model to elucidate the biochemical mechanism underlying the modulation of metabolism occurrin g through hepatocytes-Kupffer cells interactions.