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

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.