Affordable Access

Publisher Website

Species differences in hepatic glutathione depletion, covalent binding and hepatic necrosis after acetaminophen

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
14
Issue
11
Identifiers
DOI: 10.1016/0024-3205(74)90092-7
Disciplines
  • Biology

Abstract

Abstract Acetaminophen, a widely prescribed analgesic that causes fulminant hepatic necrosis in overdosed humans, produced varying degrees of hepatotoxixity in mice, rats, hamsters, guinea pigs and rabbits. The severity of hepatic injury paralleled the rate of activation of acetaminophen by hepatic microsomal enzymes to a potent arylating agent. The severity of hepatic damage in various species also correlated directly with the rate of hepatic glutathione depletion after acetaminophen. These findings support the hypothesis that the electrophilic arylating agent formed from acetaminophen in vibo is preferentially detoxified by conjugation with glutathione and that arylation of hepatic macromolecules occurs only when glutathione availability is exceeded. Since N-hydroxylation of another N-acetylarylamine (2-acetylaminofluorene) occurs to a much greater extent in the species that are susceptible to acetaminophen-induced hepatic necrosis, the data also are consistent with the hypothesis that the toxic metabolite of acetaminophen results from N-hydroxylation.

There are no comments yet on this publication. Be the first to share your thoughts.