Effects of commonly used drugs on the metabolism of selenium and copper

Project Summary

The trace elements selenium and copper are essential trace elements for humans. The liver mainly controls their metabolism, where the two micronutrients are converted into a protein-bound conformation for systemic transport. For this purpose, the hepatocytes synthesize and release the transport proteins selenoprotein P and ceruloplasmin, respectively.  An insufficient supply or a disturbance of the hepatic selenium or copper metabolism is associated with health risks and diseases. Thus, given our aging society, two fundamental questions arise about selenium and copper metabolism that need to be better characterized to reduce age-related health risks and better care for diseased individuals: (i) what biomarkers can most appropriately and reliably determine trace element supply status for selenium and copper from serum samples, and (ii) what drug/drug combinations interfere with selenium or copper metabolism and biosynthesis of the transport proteins selenoprotein P or ceruloplasmin, or both simultaneously? To address these questions, established and newly developed biomarkers of selenium and copper status will be determined in healthy and diseased individuals and associated with clinical parameters. For this purpose, a prospective cohort will be analyzed for disease risks and a cohort of diseased elderly patients will be analyzed for associations with disease parameters. In addition to these analytical studies, commonly used drugs will be investigated in cell culture using molecular methods for their potential to interfere with selenium and copper metabolism. Combinations of drugs are also used here to assess the risk of polypharmacy on trace element metabolism. Particularly critical effects will also be investigated under selenium or copper deficiency to identify protective supplementation, if necessary. Taken together, these experiments will identify appropriate avenues for improved analytics and risk assessment of selenium or copper deficiency via appropriate biomarkers, and outline the dangers and strategies for managing the risk of drugs as potential disruptors of the metabolism of these essential trace elements. Particularly critical combinations of drugs will be identified for better analysis and avoidance.