Study of Metal-Metal Interactions and Their Biomarkers Using an Intestinal Human Cell Line

From the time of dietary intake to their utilization, the number of important interactions occurs among mineral elements, which can affect their bioavailability because of similarity in physicochemical properties and common absorptive pathways. However, the studies that have analyzed the interactions among copper, iron, and zinc have conflicting results and need further exploration. HT-29 cells grown to confluence in 6-well plates were incubated with increasing concentrations (0 to 200 μM) of Cu, Fe, and Zn for 3 and 6 h for uptake studies. Interaction studies involved measuring the uptake of metal in the presence of 0:1-4:1 ratio of the other metal for 3 h using atomic absorption spectrophotometer. The concentration of metal biomarkers and cytokines was also measured in the cell lysate following extracellular supplementation. The presence of 50 μM Zn significantly decreased (P < 0.05) cellular Cu uptake in HT-29 cells at 0.5:1 Cu:Zn ratio and also the cellular Fe uptake at the ratios 0.5:1, 2:1, and 4:1 Fe:Zn. The presence of 50 μM Fe significantly (P < 0.05) decreased cellular Cu uptake at the ratios 1:1, 2:1, and 4:1 Cu:Fe. The concentration of metallothionein responded significantly (P < 0.05) to changes in extracellular Zn concentration (supplementation and depletion). There was a decrease in concentration of IL-1β and TNF-α (P < 0.05) with an increasing extracellular concentration of Cu and Fe. The results of the study indicated that the presence of one mineral in the diet and multi mineral supplement may influence the bioavailability of the other mineral. Copper and iron may find application in promoting gut health.