WA8 Exposure and Effect Endpoints
Room 19A/B, Level 4
8:00 AM - 12:00 PM, Wednesday, 12 November 2003
Chair: Williams, Bill ,
(395) Piscine intestinal zinc uptake: competition, complexation and toxicological implications.
Glover, C1, Bury, N2, Hogstrand, C2, 1 McMaster University, Hamilton, Ontario, CANADA2 King's College, London, UK
ABSTRACT- The fate of a toxicant in the gastrointestinal tract is likely to be highly dependent upon luminal composition. The diet is a complex chemical mixture the constituents of which will alter interactions of the toxicant with the uptake surface, and/or modify the fate and transport of the toxicant beyond the epithelial surface. This investigation used in vivo (intestinal perfusion) and in vitro (brush-border membrane vesicles) methods to initially characterise the mechanism of intestinal Zn(II) uptake in a freshwater teleost. Important differences between these two methods suggested that homeostatic control (mucus secretion, endocrine feedback) in intact animals may play a vital role in regulating uptake. Once uptake patterns were established, the influence of simple mixtures containing either competing cations (e.g. Cd, Cu, Ca) or complexing agents (e.g. histidine, bicarbonate) were examined. Complexation influences were qualitative, with inorganic chelation reducing Zn(II) uptake, while evidence of transport of Zn(II)-histidine moieties was found. Evidence of calcium-sensitive intestinal uptake, at environmentally realistic levels, suggested that dietary composition may play an important role in modifying the uptake, and potentially the toxicity, of Zn(II) in the gastrointestinal tract. Surprisingly, this effect did not appear to be mediated by competition at an apical calcium channel indicating a fundamentally different uptake mechanism to that at the piscine gill. Copper and cadmium had significant influences in vivo, but these effects were not exerted at an apical locus. Effects of competition and complexation on compartmental Zn(II) burden may change without an alteration in whole body burden, suggesting that significant interactions at the uptake surface and beyond may be overlooked.
Key words: zinc, Dietary metals, chemical mixtures, nutrition