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Acetaminophen‐induced hepatic injury: Protective role of glutathione in man and rationale for therapy
Author(s) -
Mitchell Jerry R.,
Thorgeirsson Snorri S.,
Potter William Z.,
Jollow David J.,
Keiser Harry
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974164676
Subject(s) - acetaminophen , glutathione , cysteamine , pharmacology , chemistry , metabolite , liver injury , nucleophile , biochemistry , medicine , enzyme , catalysis
Recent studies of acetaminophen‐induced liver damage in animals indicate that acetaminophen is converted in the liver to a chemically reactive arylating agent that normally is detoxified by conjugation with glutathione. When the dose of acetaminophen is large enough to deplete hepatic glutathione, however, there is extensive arylation of hepatic macromolecules and cell death. This paper presents evidence that administration of glutathione‐like nucleophiles, such as cysteamine, protects mice from arylation of hepatic macromolecules, hepatic necrosis, and death caused by the reactive acetaminophen metabolite. Additional studies indicate that glutathione may serve a similar protective function in man as in other animals. Thus, logical treatment of patients overdosed with acetaminophen might be based on cysteamine or other nucleophiles.