ACETAMINOPHEN DECREASES ADENOSINE 3'-PHOSPHATE 5'-PHOSPHOSULFATE AND URIDINE DIPHOSPHOGLUCURONIC ACID IN RAT-LIVER

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (1) , 35-41
Abstract
The effects of acute administration of acetaminophen [an analgesic and antipyretic drug] on adenosine 3''-phosphate 5''-phosphosulfate (PAPS) and UDP-glucuronic acid concentrations were determined in fed male rats. Acetaminophen produced a dosage-dependent decline in rat hepatic PAPS concentrations which was significant after dosages of 150, 300 or 600 mg/kg i.p. The time course of the decline in PAPS values after 600 mg acetaminophen/kg showed that PAPS concentrations reached a nadir 1 h after dosing (40% of control values). Serum sulfate concentrations were also decreased by large dosages of acetaminophen (32 and 15% of control 2 h after 150 and 600 mg/kg, respectively) and a significant, positive correlation between serum sulfate and hepatic PAPS concentrations was noted. Hepatic Cys and glutathione concentrations were lowered by high dosages of acetaminophen. Hepatic UDP-glucuronic acid concentrations were greatly decreased for 2 h after a dosage of 600 mg acetaminophen/kg (15, 23 and 42% of control 0.5, 1.0 and 2.0 h after dosing, respectively) whereas 150 mg/kg produced a less pronounced and more transient decrease. These findings demonstrate that both PAPS and UDP-glucuronic acid concentration in liver are decreased after administration of acetaminophen and imply that capacity-limited sulfation and glucuronidation of acetaminophen are due to a decrease in co-substrate availability.