Premium
Metabolic effects of acetaminophen. Studies in the isolated perfused rat liver
Author(s) -
Itinose Ana Maria,
Sakuno Marlene Leiko Doi,
Bracht Adelar
Publication year - 1989
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.290070405
Subject(s) - glycogenolysis , acetaminophen , glycogen , gluconeogenesis , chemistry , glycolysis , metabolite , metabolism , fructose , respiration , medicine , endocrinology , glycogen synthase , biochemistry , mitochondrion , glycogenesis , biology , botany
The effects of acetaminophen on the metabolism of the isolated perfused rat liver were investigated. The following results were obtained: (1) Acetaminophen increased glucose release and glycolysis from endogenous glycogen (glycogenolysis). (2) Oxygen uptake, gluconeogenesis from either pyruvate or fructose and glycogen synthesis were inhibited. (3) In isolated rat liver mitochondria acetaminophen decreased state III and state IV respiration; it also decreased the ADP/O ratio and the respiratory control ratio. (4) The action of acetaminophen on glycogenolysis was not affected by N ‐acetylcysteine; this compound, however, increased glycogen synthesis. (5) The effects of acetaminophen are reversible.It was concluded that glycogen depletion by acetaminophen can be produced by two mechanisms. The first, as previously demonstrated by several workers, depends on irreversible binding of a reactive metabolite. The second, however, is reversible and depends primarily on an inhibition of mitochondrial energy metabolism.