ORAL AND SUBCUTANEOUS ADMINISTRATION OF CADMIUM CHLORIDE AND THE DISTRIBUTION OF METALLOTHIONEIN AND CADMIUM ALONG THE VILLUS-CRYPT AXIS INRAT JEJUNUM

The route of Cd uptake influences the distribution of Cd, other metals , and metallothionein (MT). Although intestinal MT levels related to t he tissue mass did not show proximodistal gradients after sc administr ation of CdCl2, orally administered-high doses of CdCl2 increased muco sal MT levels longitudinally from the duodenum to the ileum. The gradi ent abolished when the mucosal MT level was related to the intestinal length. To further elucidate this finding, three groups of rats were s tudied: a control group, a group receiving dietary CdCl2 and a group r eceiving sc injections of CdCl2. The small intestine was removed after a 14-d treatment. Midjejunal segments were mounted in a cryomicrotome and cut transversally into five layers along the villus-crypt axis. M ucosal enzymes were measured to control these sections. Cd was measure d by AAS and MT by RIA. Alkaline phosphatase and lactase activities ex hibited the typical villus-crypt gradient. Mucosal MT levels parallele d those of Cd. Although Cd and MT concentrations were high; at the tip of the villi and low in the crypts after oral administration, sc trea tment reversed that profile. A molar Cd-MT ratio of approx 10 or 1 was reached after po or sc treatment, respectively. This demonstrates tha t only oral Cd may lead to an accumulation of Cd in the mucosal tissue fairly exceeding the binding capacity of small intestinal MT. The res ults show that different routes of Cd intake lead to a different MT-in duction pattern in the intestinal wall and that longitudinal Cd and MT concentration gradients in the small intestine observed after high or al doses are a result of their high levels at the villus tips.