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

常用药物对硒、铜代谢的影响

• 批准号: 349847280
• 负责人: Professor Dr. Lutz Schomburg
• 金额: --
• 依托单位: Institut für Experimentelle Endokrinologie (CVK)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/349847280?language=en
• 关键词: Effects; commonly; used; drugs; metabolism

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.

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，在肝脏中，膳食微量营养素被代谢成蛋白质结合形式，使其能够全身供应并运输到目标细胞。为此，肝细胞合成并分泌富硒硒蛋白P和富铜蓝蛋白。营养供应的限制或肝脏微量元素代谢的中断与健康风险和疾病有关。鉴于我们的老龄化社会，需要更详细地描述两个相关问题，以便尽量减少因硒和铜代谢紊乱而造成的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来最好地监测血清中的微量元素状态，以及ii)哪些常用药物/药物组合通过破坏硒蛋白P和铜蓝蛋白的常规生物合成来影响硒和/或铜的代谢，或两者联合使用？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已建立的和新开发的硒和铜代谢生物标志物，并与临床参数相关联。为此，我们将对前瞻性队列受试者进行疾病风险分析，并对老年患病患者进行队列疾病参数与硒、铜状态的关系研究。除了这些分析研究外，常用药物还将通过新开发的体外实验来评估其破坏常规硒和铜代谢的可能性。值得注意的是，将评估常用药物的组合是否具有破坏性。将在硒缺乏的情况下评估关键药物或药物组合，以确定补充硒或铜以改善这些破坏性影响的潜在价值。这些实验将确定并提出更可靠的硒或铜缺乏量化和风险评估的适当措施，并强调某些药物或药物组合作为常规硒和铜代谢的有效干扰物所施加的风险。将确定特别关键的药物和药物组合，这将强调有必要更好地监测这些药物与硒和铜状态的关系，并强调潜在的补充策略，以改善与微量元素代谢的不良药物作用相关的健康风险增加。