TI: Role of ATP and glycogen reserves in both paracetamol
sulfation and glucuronidation by cultured precision-cut rat liver slices.
AU: Evdokimova,-E; Taper,-H; Buc-Calderon,-P
AD: Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie,
Departement de Sciences Pharmaceutiques, Universite Catholique de Louvain,
Brussels, Belgium.
SO: Toxicol-In-Vitro. 2001 Dec; 15(6): 683-90
JN: Toxicology-in-vitro
PY: 2001
AB: Precision-cut rat liver slices (PCLS) were used to investigate
the formation of paracetamol conjugates. The time course of biochemical
markers such as ATP and GSH content, glycogen levels and protein synthesis
rates was recorded over a period of time of 26 h and taken as index of
slices viability. Low values of ATP (3.6 nmol/mg prot), GSH (7.1 nmol/mg
prot) and protein synthesis rates (94.1 pmol leu/mg prot x min(-1)) were
initially observed. Thereafter, they gradually recovered up to 6 h but
decreased values were seen after 20 h. Glycogen, however, dropped rapidly
during the first 6 h, being no longer detected after 20 h of incubation.
The reincubation of PCLS in a fresh medium for 6 h allowed a strong recovery
of GSH, ATP and protein synthesis rates, but no gluconeogenesis was observed.
Meanwhile, paracetamol sulfate formation was fairly constant (about 3 microg/mg
protein) while glucuronide gradually disappeared. The amount of both UGT1A1
and ST1A1 did not correlate with their respective enzymatic activities.
We suggest that loss of glycogen impair glucuronide conjugation by decreasing
the availability of UDPGA, and that low values of ATP are largely enough
to support sulfotransferase activity.