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

硒和铜是人体必需的两种微量元素。它们的代谢主要由肝脏控制，其中膳食微量营养素被代谢成蛋白质结合形式，以使系统供应和运输到靶细胞。为此，肝细胞合成并分泌富硒硒蛋白P和富铜铜蓝蛋白。营养供应的限制或肝脏微量元素代谢的破坏与健康风险和疾病有关。鉴于我们的社会正在老龄化，有两个相关问题需要更详细地加以说明，以尽量减少硒和铜代谢紊乱对与年龄有关的健康风险，并改善病人护理; i）如何通过合适的生物标志物最好地监测来自血清的微量元素状态，和ii）哪些常用药物/药物组合影响硒和/或硒的代谢。或通过破坏硒蛋白P和铜蓝蛋白的正常生物合成或两者结合来抑制铜代谢？为了解决这些研究问题，将从一组健康和患病受试者中确定硒和铜代谢的已建立和新开发的生物标志物，并将其与临床参数相关联。为此，将分析前瞻性受试者队列的疾病风险，并研究患病老年患者队列的疾病参数与硒和铜状态的关系。除了这些分析研究外，还将通过新开发的体外试验对常用药物进行实验评估，以确定其破坏常规硒和铜代谢的潜力。值得注意的是，将评估常用药物的组合的破坏潜力。关键药物或药物组合将在硒缺乏下进行评估，以确定硒或铜补充剂对改善这些破坏性影响的潜在价值。这些实验将确定并建议适当的措施，以更可靠地量化和评估硒或铜缺乏症的风险，并强调某些药物或药物组合作为常规硒和铜代谢的强效干扰物所产生的风险。将确定特别关键的药物和药物组合，这将强调更好地监测这些药物与硒和铜状态的必要性，并强调潜在的补充策略，以改善与药物对微量元素代谢的不良影响相关的相应增加的健康风险。

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.