对非甾体抗炎药的代谢组学反应

Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs.

作者信息

Ghosh Soumita, Lahens Nick, Barekat Kayla, Tang Soon-Yew, Theken Katherine N, Ricciotti Emanuela, Sengupta Arjun, Joshi Robin, Bushman Frederic D, Weljie Aalim, Grosser Tilo, FitzGerald Garret A

机构信息

Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.

出版信息

bioRxiv. 2024 Dec 2:2024.11.26.625478. doi: 10.1101/2024.11.26.625478.

DOI:10.1101/2024.11.26.625478

PMID:39677795

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642787/

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase -2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.

摘要

非甾体抗炎药（NSAIDs）是缓解疼痛和炎症的常用药物；然而，它们会伴随胃肠道和心血管系统的副作用。我们比较了传统NSAID萘普生和环氧化酶-2（Cox-2）抑制剂塞来昔布对人体的影响。我们的研究结果显示，服用萘普生的志愿者血浆中色氨酸和犬尿氨酸水平降低。我们在小鼠中进一步验证了这一结果。此外，我们发现色氨酸的减少与Cox-1和Cox-2的抑制均无关，而是由于萘普生取代了结合的色氨酸。在服用萘普生的小鼠中补充色氨酸可挽救粪便失血以及由心脏中的IL-1β驱动的炎症基因表达。