Oral ibuprofen differentially affects plasma and sweat lipid mediator profiles in healthy adult males

Authors: AGRAWAL, KARAN - University Of California, Davis; BOSVIEL, REMY - University Of California, Davis; PICCOLO, BRIAN - University Arkansas For Medical Sciences (UAMS); Newman, John

Submitted to: Prostaglandins & Other Lipid Mediators
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2018
Publication Date: 5/17/2018
Citation: Agrawal, K., Bosviel, R., Piccolo, B.D., Newman, J.W. 2018. Oral ibuprofen differentially affects plasma and sweat lipid mediator profiles in healthy adult males. Prostaglandins & Other Lipid Mediators. 137:1-8. https://doi.org/10.1016/j.prostaglandins.2018.05.009.
DOI: https://doi.org/10.1016/j.prostaglandins.2018.05.009

Interpretive Summary: Sweat contains molecules produced by the body, including a variety of fatty substances or lipids, which are known to regulate a wide array of biological process. How these metabolites enter the sweat is not known. Understanding where these lipid mediators are produced and how they enter the sweat will aid interpretation of their levels in sweat, which may provide novel non-invasive biomarkers of health. By studying the behavior of drugs, it is believed that ingested compounds which appear in sweat are either secreted from the blood or from the skin cells surrounding the sweat gland. However, the sweat gland itself can also produce some of lipid mediators. Here we tested whether blood was a major source of sweat lipid mediators, and determined if over the counter anti-inflammatory medication ibuprofen could change the level of inflammatory mediators in sweat. To this end we collected blood plasma and sweat from apparently healthy men immediately before, and 30 min, 2 hr and 4 hr after they consumed 400 mg of ibuprofen by mouth. We measured concentrations of ibuprofen and ~100 lipid mediators in the collected plasma and sweat by mass spectrometry. We detected approximately 45 lipid mediators in both plasma and sweat, 36 of which were found in both. Before ibuprofen consumption the concentrations and relative abundance of the 36 lipid mediators which were common to both matrices differed in plasma and sweat. Consistent with the pharmacological effects of ibuprofen, consumption of this drug caused changes in concentrations of specific oxylipins (i.e. prostaglandin E2, 11-hydroxyeicosatetraenoic acid and 20-hydroxyeicosatetraenoic acid) and nitrolipids (9-nitrooleate) in sweat. Similar effects in plasma were not observed. Additionally, ibuprofen consumption decreased concentrations of specific endocannabinoids (i.e. oleoylethanolamide and linoleoylethanolamide) in sweat and increased concentrations of these same compounds in plasma. As the measured mediators are generally short lived and locally produced this result suggests that they were derived from local tissues and not the associated blood supply. Collectively, these experiments demonstrate that blood and sweat provide different biochemical information regarding ibuprofen consumption, and that blood is unlikely to be the predominant source of the sweat lipid mediator profile

Technical Abstract: Sweat contains a variety of lipid mediators, but whether they originate from the plasma filtrate or from the cutaneous sweat glandular tissues themselves is unknown. To explore this knowledge gap, we collected plasma and sweat from healthy men (n = 9) immediately before and 0.5, 2 and 4 h after oral administration of 400 mg ibuprofen. Of the over 100 lipid mediators assayed by liquid chromatography-tandem mass spectrometry, ~45 were detected in both plasma and sweat, and 36 were common to both matrices. However, baseline concentrations in each matrix were not correlated and metabolite relative abundances between matrices differed. Oral ibuprofen administration altered sweat lipid mediators, reducing prostaglandin E2, linoleoylethanolamide, and oleoylethanolamide, while increasing 11-hydroxyeicosatetraenoic acid, and causing transient changes in 9-nitrooleate, N arachidonylglycine and 20-hydroxyeicosatetraenoic acid. Meanwhile, plasma N-acylethanolamide concentrations increased with ibuprofen administration. These results suggest that sweat and plasma differentially reflect biochemical changes due to oral ibuprofen administration, and that plasma is unlikely to be the predominant source of the sweat lipid mediator profile.