Biological Trace Element Research

, Volume 21, Issue 1, pp 317–323 | Cite as

Subclinical response to cadmium in liver cells

  • Ludwig Müller
  • Neill H. Stacey
Section 4 Mechanisms of Metal Toxicity


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 of 0.2 μmol Cd/kg and by incubation of isolated hepatocytes with up to 25 μM 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 μM Cd decreased CYT C OX but not mitochondrial PrH. Moreover, simultaneous incubation of hepatocytes with 25 μM 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 μM 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.

Index Entries

Cadmium toxicity metallothionein thiol agents, cytochrome c oxidase protoheme 









reduced glutathione






cytochrome c oxidase






sorbitol dehydrogenase


atomic absorption spectrometer


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Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • Ludwig Müller
    • 1
  • Neill H. Stacey
    • 2
  1. 1.Institute of ToxicologyUniversity of DüsseldorfDüsseldorfFRG
  2. 2.National Institute of Occupational Health and SafetyThe University of SydneyAustralia

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