ALTERATIONS IN INTESTINAL UPTAKE AND COMPARTMENTALIZATION OF ZINC IN RESPONSE TO SHORT-TERM DEXAMETHASONE THERAPY OR EXCESS DIETARY ZINC IN PIGLETS

Premature infants receive high dietary zinc and often glucocorticoids as a treatment for chronic lung disease. A piglet model was developed to investigate intestinal zinc transport and distribution of tissue zinc in response to treatment with short-term (5 d) glucocorticoid therapy or a high zinc diet. Piglets (13-15 d old; n = 21) were randomly allocated to: 1) dexamethasone (DEX) therapy (1.5 mg/kg intramuscularly twice a day), 2) high zinc diet (15.3 mmol/kg), or 3) control group (0.3 mmol dietary zinc/kg and saline intramuscularly twice a day). Pig weight, formula intake, urine volume, and blood glucose were monitored. At necropsy, tissue samples were obtained to measure zinc in plasma and zinc and metallothionein in liver and small intestinal mucosa. Velocity of zinc uptake by intestinal brush border membrane vesicles was measured using Zn-65 tracer. Maximum uptake rate and Km for zinc uptake by brush border membrane vesicles were significantly greater (p < 0.05) in DEX compared with control and high zinc groups. DEX-treated piglets had a significantly lower (p < 0.05) zinc efflux rate across brush border membrane vesicles compared with that of the control. The high zinc group had a higher liver (p < 0.05) and mucosal (p < 0.05) zinc content and higher liver metallothionein concentration (p < 0.001) compared with the control and DEX groups. Weight gain over 5 d was not different among groups. Daily blood glucose was higher (p < 0.05) in DEX versus control and high zinc groups. Short-term DEX treatment induced changes in mucosal uptake of zinc that are consistent with up-regulation of specific mucosal proteins, but this was not the case with metallothionein. These alterations in zinc metabolism may have consequences for zinc status in premature infants who receive glucocorticoids such as DEX and/or high zinc diets.