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Randomized Controlled Trial
. 2025 Jun 1;57(6):1092-1102.
doi: 10.1249/MSS.0000000000003659. Epub 2025 Jan 29.

Effect of Ibuprofen on Markers of Acute Kidney Injury, Intestinal Injury, and Endotoxemia after Running in the Heat

Affiliations
Randomized Controlled Trial

Effect of Ibuprofen on Markers of Acute Kidney Injury, Intestinal Injury, and Endotoxemia after Running in the Heat

Jonathan W Specht et al. Med Sci Sports Exerc. .

Abstract

Purpose: To test the hypothesis that ibuprofen ingestion exacerbates markers of acute kidney injury (AKI), gastrointestinal (GI) injury, and endotoxemia after running in the heat.

Methods: Using a randomized double-blind crossover design, 11 physically active individuals (six women) ingested 600 mg of ibuprofen or placebo 12- and 1-h before running 1 h in a heated chamber (35°C, 20%-60% R.H.) at an intensity of 60% V̇O 2peak . Blood and urine samples were collected preexercise, postexercise, and 1-h postexercise to assess cytokines and markers of AKI, GI injury, and endotoxemia.

Results: One hour of running in the heat increased markers of AKI (urinary product of IGFBP7•TIMP2 [Placebo: ∆ 1.8 ± 0.8 log 10 (ng·mL 2 )/1000, Ibuprofen: ∆ 1.8 ± 0.9 log 10 (ng·mL 2 )/1000], urinary NGAL, and serum cystatin C), GI damage (I-FABP [Placebo: ∆ 631 ± 446 pg·mL -1 , Ibuprofen: ∆ 576 ± 455 pg·mL -1 ]), and inflammatory cytokines (TNFα [Placebo: ∆ 5.2 ± 3.5 pg·mL -1 , Ibuprofen: ∆ 6.2 ± 4.9 pg·mL -1 ], IL-6, IL-10, and MCP-1), but these changes were not exacerbated by ibuprofen ingestion. There were effects of time ( P < 0.001) and condition ( P = 0.03) for serum IL-8, with greater concentrations in the ibuprofen (pre: 11.4 ± 5.1 pg·mL -1 , post: 15.5 ± 7.3 pg·mL -1 ) trials than placebo (pre: 9.7 ± 4.2 pg·mL -1 , post: 11.7 ± 5.4 pg·mL -1 ). There were no effects of time or condition on markers of endotoxemia (LBP [Placebo: ∆ -1.2 ± 3.2 μg·mL -1 , Ibuprofen: ∆ 1.0 ± 1.6 μg·mL -1 ], sCD14).

Conclusions: These findings indicate that ibuprofen ingestion does not worsen intestinal or renal injury experienced during 1 h of exercise in the heat, but increases pro-inflammatory IL-8.

Keywords: CYTOKINE; EXERCISE; EXERTIONAL HEAT STRESS; NSAID.

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Conflict of interest statement

This study was partially funded by Wilderness Medical Society and the Academy of Wilderness Medicine, the University of New Mexico’s Graduate and Professional Student Association, the Rocky Mountain American College of Sports Medicine regional chapter, and R01OH011528 (to ZJS). ZJM was funded by the National Institutes of Health Grant F32HL168826. ZJS has received consultant fees from Otsuka Holdings Co., Ltd.

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