Toxic and biochemical effects of zinc in Caco-2 cells.
Zinc (in relatively high concentrations) can be toxic to intestinal cells. The aim of the present study was to quanitfy cellular injury in preconfluent, colonic cancerous cells and in postconfluent, differentiating human intestinal Caco-2 cells. Cellular damage was measured by using cell proliferation, lactate dehydrogenase (LDH)-release, and apoptosis studies. Furthermore, the activities of the major antioxidative enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase] and differentiation markers (alkaline phosphatase and aminopeptidase-N) were determined after exposure of the cells to increasing amounts of zinc sulfate. Proliferation and viability decreased in a concentration-dependent manner. A noticeable increase of LDH-release correlated to cell rounding and detachment at relatively high zinc levels (200 muM) was observed in both groups of cells. Above 100 muM of zinc, significant apoptotic activity was found in the preconfluent cells. Zinc supplementation did not alter SOD activities. However, GPx and, in part, catalase activities tended to be higher in zinc-treated cells (nevertheless the results were not significant). Differentiation markers were noticeably induced by increasing amounts of zinc, especially in the preconfluent cells. In conclusion, we suggest that the susceptibility to zinc induced damage is equal in both confluentation groups of Caco-2 cells. Risk assessment for high concentrations seems recommendable.
Department of Physiology, Faculty of Medicine, University of Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. bettina.zoedl@univie.ac.at
Bettina
B
Zödl
Michaela
M
Zeiner
Mansour
M
Sargazi
Norman B
NB
Roberts
Wolfgang
W
Marktl
Ilse
I
Steffan
Cem
C
Ekmekcioglu
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D018826:CD13 Antigens / Q000187:drug effects / Q000378:metabolism; D018938:Caco-2 Cells; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity
D015415:Biomarkers; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D018826:CD13 Antigens; D015032:Zinc