Abstract

The parenteral administration of a toxic dose of the calcium chelate of ethylenediaminetetracetate (CaEDTA) to rats caused a marked increase in the permeability of the intestinal wall to normally nonpermeating solutes. By contrast, the administration of an equi m dose of CrEDTA, a highly stable and inert chelate that does not undergo metal exchange in vivo, did not produce any observable toxic effects, and the permeability of the intestine was not affected. The possibility was investigated that either deposition or depletion of metals or a derangement of the connective tissue matrix might explain the enhanced permeability of the intestinal wall. Although no significant changes in metal concentrations of the intestinal wall were measured, the study did not rule out the possibility of an inactivation of metals in situ due to the formation of ternary complexes. The urinary excretion of hydroxyproline, an imino acid virtually specific for collagen, increased approximately 6-fold in rats treated with CaEDTA, When proline- 14C was administered 1 mo preceding treatment with CaEDTA, the urinary excretion of hydroxyproline- 14C increased, but its specific activity remained unchanged. The urinary excretion of hydroxyproline was not affected by the administration of CrEDTA. Thus it seems that CaEDTA effects collagen degradation by virtue of its chelating property.

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