title: Subclinical response to cadmium in liver cells.
abstract: Effects of cadmium (Cd) in vivo and in vitro were studied in the absence of enhanced metallothionein (MT) production and overt Cd toxicity. Such a condition was established by extended oral exposure of male rats to 0.2 mumols Cd/kg and by incubation of isolated hepatocytes with up to 25 microM for 30 min. Subsequently, mitochondrial and extramitochondrial responses to Cd were recorded. Cadmium diminished the activity of cytochrome c oxidase (CYT C OX) by 50% in vivo and by 35% in vitro. In hepatocytes, this was accompanied by increased Cd and decreased protoheme (PrH) in mitochondria. Extramitochondrial PrH and cytochrome P 450 were not significantly altered. In hepatocytes from phenobarbitone pretreated rats, 25 microM Cd decreased CYT C OX but not mitochondrial PrH. Moreover, stimultaneous incubation of hepatocytes with 25 microM Cd and either 2.5 mM dithiothreitol or 5 mM reduced glutathione diminished cellular and mitochondrial Cd and prevented the decrease in CYT C OX but not that in PrH. In contrast, coincubation with either 250 microM L-buthionine-sulfoximine or diethylmaleate, which did not alter Cd uptake, prevented the decrease in PrH but not that in CYT C OX owing to Cd. These results show that Cd exerts mitochondrial alterations in vivo and in vitro in the absence of enhanced MT production. Moreover, Cd effects on CYT C OX and PrH do not seem to be firmly linked.
authors.affiliation: Institute of Toxicology, University of Düsseldorf, FRG.
authors.forename: L
authors.initials: L
authors.lastname: Müller
authors.forename: N H
authors.initials: NH
authors.lastname: Stacey
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis; D008099:Liver / Q000166:cytology*; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D013438:Sulfhydryl Compounds; D002104:Cadmium; D006418:Heme; D008668:Metallothionein; D003576:Electron Transport Complex IV; D010634:Phenobarbital