title: Increased levels of hepatic metallothionein in rat and mouse after injection of acetaminophen.
abstract: Induction of hepatic metallothionein (MT) by acetaminophen was characterized in the rat and mouse. Treatment of rats with the hepatotoxin resulted in increase of liver MT in a dose-dependent manner. MT concentration was elevated by 41%, 140% and 260% following acetaminophen injection at doses of 250, 500 and 1000 mg/kg, respectively. The cadmium-binding protein was identified as MT by Sephadex G-75 gel filtration (Ve/Vo = 2.1). In the mouse the hepatotoxin was more potent i.e. maximal effect (increase of 230%) was achieved at the lowest applied dose (250 mg/kg). In both species maximal induction was observed 24 h post exposure and thereafter the hepatic MT content declined, indicating a relatively short half-life of the protein. The elevation of the intracellular concentration of a sulfhydryl-rich protein such as MT may serve as self protecting mechanism of the hepatocyte against highly reactive metabolites of toxic substances.
authors.affiliation: Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Wormser
authors.forename: D
authors.initials: D
authors.lastname: Calp
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000082:Acetaminophen; D008668:Metallothionein