title: Copper, but not cadmium, is acutely toxic for trout hepatocytes: short-term effects on energetics and ion homeostasis.
abstract: The toxic effects of cadmium (Cd) and copper (Cu) on cellular energy metabolism and ion homeostasis were investigated in hepatocytes from the rainbow trout, Oncorhynchus mykiss. The metal content of cells did not increase during incubation with Cu, whereas a dose-dependent increase was seen with Cd. Cell viability was unaffected in the presence of 100 microM Cd and 10 microM Cu but was significantly reduced after 30 min of exposure to 100 microM Cu, both in the presence and absence of extracellular calcium. Oxygen consumption (VO(2)) was not affected by 100 microM Cd or 10 microM Cu, whereas 100 microM Cu caused a significant and calcium-dependent increase of VO(2). Lactate production and basal glucose release were not altered by either of the metals. However, the epinephrine-stimulated rate of glucose release was significantly reduced after 2 h of incubation with 100 microM Cu. Hepatocytes exposed to Cd showed only a marginal increase of intracellular free calcium (Ca(i)(2+)), whereas with Cu a pronounced and dose-dependent increase of Ca(i)(2+) was induced after a delay of 10 to 15 min, the calcium being of extracellular origin. Intracellular pH was not altered by Cd but decreased significantly in the presence of Cu. Overall our data demonstrate that Cu, but not Cd, is acutely toxic for trout hepatocytes. Since Cu does not enter the cells in the short term it appears to exert its acutely toxic effects at the cell membrane. Although Cu toxicity is associated with an uptake of calcium from extracellular space, leading to an elevation of cellular respiration, cytotoxicity does not appear to be dependent on the presence of extracellular calcium.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000493:pharmacokinetics / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000322:Adrenergic Agonists; D002104:Cadmium; D019344:Lactic Acid; D003300:Copper; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium; D004837:Epinephrine