Time-course studies of pancreatic exocrine damage induced by excess dietary zinc in the chick

Experiments were conducted to determine the time course of Zn-induced changes in the exocrine status of the chick pancreas. In experiments 1 and 2, chicks killed at intervals after the addition of excess Zn (500 mg/kg as ZnO) to a purified diet containing 70 mg Zn/kg showed a rapid increase in plasma Zn concentration that reached a plateau within 1 h. The pancreatic soluble Zn level increased linearly for 24 h, but then its rate of accumulation diminished. The same pattern of accumulation was shown by pancreatic metallothionein (MT), which correlated highly with pancreatic Zn; that is, MT-associated Zn consistently accounted for 70 to 80% of pancreatic Zn. Plasma amylase activity started to increase 8-10 h after Zn introduction and reached a maximum by 24 h. Two critical levels of pancreatic soluble Zn (1 and 2.7 μg Zn/mg of protein, respectively) were observed at which amylase activities increased in the plasma and decreased in the pancreas. In experiment 3, feeding excess Zn reduced the incorporation of [³H]leucine into pancreatic amylase protein. This was associated with a reduction of tracer incorporation into total pancreatic proteins, that is, the fraction that is precipitable by trichloracetic acid (TCA). In experiment 4, the enzyme (or potential) activities of the exportable Zn-containing enzymes procarboxypeptidases A and B and ribonuclease were not affected by excess Zn intake, indicating the selective nature of the effect of excess Zn on pancreatic function.