Transcriptional Response to Non-Steroidal Anti-Inflammatory Drugs and Tryptophan Supplementation

Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by adverse effects in the gastrointestinal and cardiovascular systems. We compared the effects of placebo, naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase (COX)-2 inhibitor, in the plasma of healthy volunteers. We found a decrease in tryptophan and kynurenine levels in the plasma of those volunteers treated with naproxen. Based on these findings we treated mice with control, celecoxib, or naproxen diets, and examined their effects on the heart and jejunum transcriptomes. Additionally, we tested if tryptophan treatment rescued the transcriptional effects of naproxen treatment. Overall design: RNA-Seq profiling of heart or jejunum tissue from female C57BL/6 mice following three weeks of treatment with celecoxib, naproxen, tryptophan, naproxen + tryptophan, or control. Celecoxib and naproxen treatments were provided through diet, while tryptophan treatment was administered through intraperitoneal injection. Tissue samples were collected and sequenced in four different experimental batches with 5-8 mice per combination of treatment and experiment. The first experimental batch collected from heart tissue of mice treated with control or naproxen diets also included 5 male mice per treatment.