PMID- 11698170 OWN - NLM STAT- MEDLINE DCOM- 20020131 LR - 20190916 IS - 0887-2333 (Print) IS - 0887-2333 (Linking) VI - 15 IP - 6 DP - 2001 Dec TI - Role of ATP and glycogen reserves in both paracetamol sulfation and glucuronidation by cultured precision-cut rat liver slices. PG - 683-90 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. FAU - Evdokimova, E AU - Evdokimova E AD - Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement de Sciences Pharmaceutiques, Universite Catholique de Louvain, Brussels, Belgium. FAU - Taper, H AU - Taper H FAU - Buc Calderon, P AU - Buc Calderon P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Analgesics, Non-Narcotic) RN - 0 (Glucuronides) RN - 0 (Ugt1a1 protein, rat) RN - 2616-64-0 (Uridine Diphosphate Glucuronic Acid) RN - 362O9ITL9D (Acetaminophen) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9005-79-2 (Glycogen) RN - EC 2.4.1.- (UGT1A1 enzyme) RN - EC 2.4.1.17 (Glucuronosyltransferase) RN - EC 2.8.2.1 (Arylsulfotransferase) RN - GAN16C9B8O (Glutathione) SB - IM MH - Acetaminophen/*metabolism MH - Adenosine Triphosphate/analysis/*metabolism MH - Analgesics, Non-Narcotic/*metabolism MH - Animals MH - Arylsulfotransferase/analysis/*metabolism MH - Glucuronides/metabolism MH - Glucuronosyltransferase/analysis/*metabolism MH - Glutathione/metabolism MH - Glycogen/analysis/*metabolism MH - Immunoblotting MH - In Vitro Techniques MH - Liver/chemistry/drug effects/*enzymology MH - Male MH - Protein Biosynthesis MH - Rats MH - Rats, Wistar MH - Uridine Diphosphate Glucuronic Acid/metabolism EDAT- 2001/11/08 10:00 MHDA- 2002/02/01 10:01 CRDT- 2001/11/08 10:00 PHST- 2001/11/08 10:00 [pubmed] PHST- 2002/02/01 10:01 [medline] PHST- 2001/11/08 10:00 [entrez] AID - S0887-2333(01)00091-1 [pii] AID - 10.1016/s0887-2333(01)00091-1 [doi] PST - ppublish SO - Toxicol In Vitro. 2001 Dec;15(6):683-90. doi: 10.1016/s0887-2333(01)00091-1.