| 16555952 |
Wang SS, Chen L, Xia SK: Cadmium is acutely toxic for murine hepatocytes: effects on intracellular free Ca (2+) homeostasis. Physiol Res. 2007;56(2):193-201. Epub 2006 Mar 23.
We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca (2+) concentration ([Ca (2+)](i)) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl (2), 5, 10, 25 microM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p <0.05 for 25 microM CdCl (2) vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 microM CdC1 (2)-exposed groups were observed (p <0.05 and p <0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC1 (2) treatment. The Ca (2+) concentrations in the culture medium of CdCl (2)-exposed hepatocytes were significantly decreased, while [Ca (2+)](i) appeared to be significantly elevated (p <0.05 or p <0.01 vs. control). We found that in Ca (2+)-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl (2) elicited [Ca (2+)](i) increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca (2+)-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl (2) caused a mild [Ca (2+)](i) elevation in the absence of an initial rise phase. Removal of extracellular Ca (2+) showed that CdCl (2) induced an initially slow [Ca (2+)](i) rise alone without being followed by a markedly elevated phase, but in a Ca (2+)-free HBSS with addition of 2-APB, CdCl (2) failed to elicit the [Ca (2+)](i) elevation. These results suggest that abnormal Ca (2+) homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca (2+)](i) elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca (2+) entry and an excessive release of Ca (2+) from intracellular stores. |
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