bioRxivSystems BiologyPreprint
Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs
Soumita GhoshiD, Nick Lahens, Kayla Barekat, Soon‐Yew Tang, Katherine N. ThekeniD, Emanuela RicciottiiD, Arjun SenguptaiD, Robin JoshiiD, Frederic D. BushmaniD, Aalim M. WeljieiD, Tilo GroßeriD, Garret A. FitzGeraldiD
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-1{beta} in the heart.
- organism: human
- organism: mouse
- assay: metabolomics
- research focus: differential expression
- research focus: drug response / drug discovery
- approach: statistical model
- Citations
- 1
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