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Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs

Ghosh, S.; Lahens, N.; Barekat, K.; Tang, S.-Y.; Theken, K. N.; Ricciotti, E.; Sengupta, A.; Joshi, R.; Bushman, F. D.; Weljie, A.; Grosser, T.; FitzGerald, G. A.

2024-12-02 systems biology
10.1101/2024.11.26.625478 bioRxiv
Show 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.

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The top 6 journals account for 50% of the predicted probability mass.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.