Ibuprofen bioconcentration and prostaglandin E2 levels in the bluntnose minnow Pimephales notatus

Prostanoids are oxygenated derivatives of arachidonic acid with a wide range of physiological effects in vertebrates including modulation of inflammation and innate immune responses. Nonsteroidal anti-inflammatory drugs (NSAIDs) act through inhibition of cyclooxygenase (COX) conversion of arachidonic acid to prostanoids. In order to better understand the potential of environmental NSAIDS for interruption of normal levels of COX products in fishes, we developed an LC/MS/MS-based approach for tissue analysis of 7 prostanoids. Initial studies examining muscle, gut and gill demonstrated that prostaglandin E2 (PGE2) was the most abundant of the measured prostanoids in all tissues and that gill tissue had the highest and most consistent concentrations of PGE2. After short-term 48-h laboratory exposures to nominal concentrations of 5, 25, 50 and 100 mu g/L ibuprofen, 50 mu g/L and 100 mu g/L exposure concentrations resulted in significant reduction of gill tissue PGE2 concentration by approximately 30% and 80% respectively. The lower exposures did not result in significant reductions when compared to unexposed controls. Measured tissue concentrations of ibuprofen indicated that this NSAID had little potential for bioconcentration (BCF = 1.3) and the IC50 of ibuprofen for inhibition of PGE2 production in gill tissue was estimated to be 0.4 mu M. (C) 2010 Elsevier Inc. All rights reserved.