Project Details
Projekt
Effects of commonly used drugs on the metabolism of selenium and copper
Applicant
Professor Dr. Lutz Schomburg
Subject Area
Endocrinology, Diabetology, Metabolism
Nutritional Sciences
Nutritional Sciences
Term
from 2017 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 316442145
Selenium and copper are two essential trace elements for humans. Their metabolism is mainly controlled by liver where the dietary micronutrients are metabolized into a protein-bound form for enabling the systemic supply and transport to target cells. To this end, hepatocytes synthesize and secrete selenium-rich selenoprotein P and Cu-rich ceruloplasmin. A limitation in the nutritional supply or a disruption of hepatic trace element metabolism is associated with health risks and disease. In view of our ageing society, two relevant issues need to be characterized in more detail in order to minimize-age-related health risks from a disturbed metabolism of selenium and copper and to improve patient care; i) how best to monitor the trace element status from serum by suitable biomarkers, and ii) which commonly used drugs/drug combinations affect selenium and/or copper metabolism via disrupting the regular biosynthesis of selenoprotein P and ceruloplasmin or both in combination? In order to address these research issues, established and newly developed biomarkers of the selenium and copper metabolism will be determined from a set of healthy and diseased subjects and associated to clinical parameters. To this end, a prospective cohort of subjects will be analyzed in respect to disease risks, and a cohort of diseased elderly patients will be studied for the relation of disease parameters with the selenium and copper status. Besides these analytical studies, commonly used drugs will be experimentally evaluated by newly developed in vitro assays for their potential to disrupt regular selenium and copper metabolism. Notably, combinations of commonly used drugs will be assessed for their disruptive potential. Critical drugs or drug combinations will be evaluated under Se deficiency, in order to identify the potential value of selenium or copper supplementation to ameliorate these disruptive effects. These experiments will identify and suggest suitable measures for a more reliable quantification and risk assessment of selenium or copper deficiency, and highlight the risks exerted by certain drugs or drug combinations as potent disruptors of regular selenium and copper metabolism. Particularly critical drugs and drug combinations will be identified, which will emphasize the necessity for a better monitoring of these drugs in relation to selenium and copper status, and highlight potential supplementation strategies for ameliorating the respectively increased health risks associated with the adverse drug effects on trace element metabolism.
DFG Programme
Research Units
