title: Prolonged acetaminophen ingestion by mice fed a methionine-limited diet does not affect iron-induced liver lipid peroxidation or S-adenosylmethionine.
abstract: This study determined whether acetaminophen (ACAP)-induced glutathione depletion was associated with liver lipid peroxide formation, or the concentrations of liver S-adenosylmethionine and S-adenosylhomocysteine in mice fed diets with L-methionine below or at the requirement level (0.25 or 0.5%) for 7 wk. Iron dextran (281 mg/kg body wt) or saline was administered for 2 d before measurement of lipid peroxide formation. Chronic dietary ACAP (0.5%) in mice fed 0.25% methionine caused a failure to maintain body weight even though food intake was similar to intake by all other treatment groups. Liver GSH (measured as nonprotein sulfhydryl concentration) and cysteine concentrations were depleted by ACAP and by ACAP plus iron. Liver lipid peroxide formation was increased by iron but was not altered additionally by ACAP ingestion. Liver glutathione peroxidase activity was increased by methionine in controls, whereas glutathione S-transferase activity was increased by ACAP ingestion in mice fed 0.5% methionine compared with controls. Liver S-adenosylmethionine and nuclear 5-methyldeoxycytidine concentrations were not affected by dietary ACAP or methionine. Liver S-adenosylhomocysteine levels were lower in mice fed ACAP and 0.25% methionine compared with mice fed ACAP and 0.5% methionine. In conclusion, chronic ACAP did not increase the susceptibility of mice to liver lipid peroxidation or alter the availability of methyl groups for methylation reactions.
authors.affiliation: Food and Drug Administration, Washington, DC 20204.
authors.forename: M M
authors.initials: MM
authors.lastname: Reicks
authors.forename: F R
authors.initials: FR
authors.lastname: Fullerton
authors.forename: L A
authors.initials: LA
authors.lastname: Poirier
authors.forename: P
authors.initials: P
authors.lastname: Whittaker
authors.forename: J N
authors.initials: JN
authors.lastname: Hathcock
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D051379:Mice; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000082:Acetaminophen; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D007501:Iron; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D003545:Cysteine