Manzl Claudia, Ebner Hannes, Köck Günter, Dallinger Reinhard, Krumschnabel Gerhard
Abteilung für Okophysiologie, Universität Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
Toxicol Appl Pharmacol. 2003 Sep 15;191(3):235-44. doi: 10.1016/s0041-008x(03)00247-3.
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.
研究了镉（Cd）和铜（Cu）对虹鳟（Oncorhynchus mykiss）肝细胞能量代谢和离子稳态的毒性作用。在与铜孵育期间，细胞中的金属含量没有增加，而镉则呈现剂量依赖性增加。在存在100微摩尔/升镉和10微摩尔/升铜的情况下，细胞活力未受影响，但在暴露于100微摩尔/升铜30分钟后，无论有无细胞外钙，细胞活力均显著降低。100微摩尔/升镉或10微摩尔/升铜对耗氧量（VO₂）没有影响，而100微摩尔/升铜导致VO₂显著且依赖于钙的增加。两种金属均未改变乳酸生成和基础葡萄糖释放。然而，在与100微摩尔/升铜孵育2小时后，肾上腺素刺激的葡萄糖释放速率显著降低。暴露于镉的肝细胞仅显示细胞内游离钙（Ca(i)²⁺）略有增加，而铜则在延迟10至15分钟后诱导Ca(i)²⁺显著且剂量依赖性增加，钙来源于细胞外。镉未改变细胞内pH，但铜存在时细胞内pH显著降低。总体而言，我们的数据表明，铜而非镉对虹鳟肝细胞具有急性毒性。由于铜在短期内不会进入细胞，它似乎在细胞膜上发挥其急性毒性作用。尽管铜毒性与从细胞外空间摄取钙有关，导致细胞呼吸增加，但细胞毒性似乎不依赖于细胞外钙的存在。
