title: Effect of acetaminophen hepatotoxicity on hepatic mitochondrial and microsomal calcium contents in mice.
abstract: The effect of toxic doses of acetaminophen on hepatic intracellular calcium compartmentation were studied in mice. No effects on the calcium contents of the mitochondria, microsomes or cytosol were observed 4 h after the administration of 175 and 375 mg/kg acetaminophen when compared to saline-treated controls. However, doses of 500 and 750 mg/kg of acetaminophen increased mitochondrial calcium contents at this time. Also, the 750 mg/kg dose caused marked alterations in the calcium contents of microsomal and cytosolic compartments. The time-course of the onset of these effects was examined using a 500 mg/kg dose. No changes in either mitochondrial, microsomal or cytosolic calcium contents were observed in the livers of mice treated with acetaminophen compared to saline-treated controls at either 1 or 2 h after dose administration. However, at 3, 4 and 24 h after acetaminophen, mitochondrial and cytosolic calcium contents were significantly increased above control values. The increases in mitochondrial and cytosolic calcium contents observed in the acetaminophen-intoxicated mouse liver appear to occur at the same time as the appearance of plasma membrane damage, as measured by sorbitol dehydrogenase leakage. The data suggest that a perturbation in hepatic calcium compartmentation is not an early event in acetaminophen-induced hepatotoxicity in the mouse.
authors.affiliation: Department of Pharmacology, Queen Elizabeth II Medical Centre, University of Western Australia, Nedlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Burcham
authors.forename: A W
authors.initials: AW
authors.lastname: Harman
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000082:Acetaminophen; D002251:Carbon Tetrachloride; D007064:L-Iditol 2-Dehydrogenase; D002118:Calcium