Subclinical response to cadmium in liver cells
- 24 Downloads
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 EntriesCadmium toxicity metallothionein thiol agents, cytochrome c oxidase protoheme
- CYT C OX
cytochrome c oxidase
atomic absorption spectrometer
Unable to display preview. Download preview PDF.
- 4.G. S. Wagner, M. L. Dinamarca, and T. R. Tephly,Porphyrins in Human Diseases, Doss, ed., pp. 111–122, Karger, Basel, 1976.Google Scholar
- 13.M. Asada and J. T. Galambos,Gastroenterol. 44, 578 (1963).Google Scholar
- 14.T. Omura and R. Sato,J. Biol. Chem. 239, 2370 (1963).Google Scholar
- 15.R. J. Porra and O. T. G. Jones,Biochem. J. 87, 182 (1963).Google Scholar
- 19.C. A. Tyson,Toxicol. Ind. Hlth. 3, 459 (1987).Google Scholar