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Acetaminophen does not decrease hepatic 3'-phosphoadenosine 5'-phosphosulfate in mice

H J Kim¹, P Rozman, C D Klaassen

¹Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA.

The Journal of Pharmacology and Experimental Therapeutics

|December 1, 1995

Summary

Acetaminophen decreases sulfate levels in mice but does not affect 3'-phosphoadenosine 5'-phosphosulfate (PAPS) levels, indicating sulfation is not PAPS-limited in mice. Species differences in drug metabolism regulation exist between rats and mice.

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Area of Science:

Pharmacology
Biochemistry
Drug Metabolism

Background:

Sulfation capacity is often limited by 3 -phosphoadenosine 5 -phosphosulfate (PAPS) availability.
PAPS availability is thought to be limited by inorganic sulfate precursor levels.
Previous studies in rats suggested acetaminophen (AA) affects PAPS and sulfate concentrations.

Purpose of the Study:

To investigate the effects of acetaminophen (AA) on PAPS and inorganic sulfate concentrations in mice.
To determine if AA sulfation in mice is limited by PAPS availability.
To compare AA sulfation regulation between mice and rats.

Main Methods:

Mice were administered varying doses of acetaminophen (AA).
Serum and liver concentrations of inorganic sulfate were measured.

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Hepatic concentrations of PAPS were quantified.

Main Results:

Acetaminophen administration significantly reduced serum and liver sulfate concentrations by approximately 50% in mice.
Contrary to findings in rats, acetaminophen did not decrease hepatic PAPS concentrations in mice.
Hepatic sulfation of high-dose AA in mice was not limited by PAPS availability.

Conclusions:

Acetaminophen decreases inorganic sulfate levels but not PAPS levels in mice.
Hepatic sulfation of acetaminophen in mice is not limited by PAPS availability.
Significant species-specific differences exist in the regulation of acetaminophen sulfation between rats and mice.