Acute toxicity of hexavalent chromium in isolated teleost hepatocytes.
Acute toxic effects of hexavalent chromium [Cr(VI)], a widely recognised carcinogenic, mutagenic and redox active metal, were investigated in isolated hepatocytes of goldfish (Carassius auratus). Exposure to 250 microM Cr(VI) induced a significant decrease of cell viability from 94% in controls to 88% and 84% after 30 min and 4 h of exposure, respectively. Cr-toxicity was associated with a concentration-dependent stimulation of the formation of reactive oxygen species (ROS). As one potential source of ROS formation we identified the lysosomal Fe(2+) pool, since the ferric ion chelator deferoxamin inhibited ROS formation by approximately 15%. Lysosomal membranes remained nevertheless intact during Cr-exposure, as determined from neutral red retention in this compartment. Another significant source of ROS appear to be the mitochondria, where a presumably uncoupled increase of respiration by 20-30% was triggered by the metal. Inhibition of mitochondrial respiration by cyanide caused an approximately 40% decrease of Cr-induced ROS-formation, whereas the uncoupling agent carbonyl cyanide m-chlorophenyl hydrazine was without effect. Cellular Ca(2+) homeostasis was not disturbed by Cr(VI) and thus played no role in this scenario. Overall, our data show that Cr(VI) is acutely toxic to goldfish hepatocytes, and its toxicity is associated with the induction of radical stress, presumably involving lysosomes and mitochondria as important sources of ROS formation.
Krumschnabel
Gerhard
G
Institut für Zoologie und Limnologie, Abteilung für Okophysiologie, Center for Molecular Biosciences Innsbruck (CMBI), Universität Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria. gerhard.krumschanbel@uibk.ac.at
Nawaz
Muhammad
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D003486:Cyanides / Q000494:pharmacology; D006054:Goldfish / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D014475:Uncoupling Agents / Q000494:pharmacology
D003486:Cyanides; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D002857:Chromium; C074702:chromium hexavalent ion; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D007501:Iron; D002118:Calcium