Uptake from water, biotransformation, and biliary excretion of pharmaceuticals by rainbow trout

Abstract

An urgent need exists to assess the exposure of fish to pharmaceuticals. The aim of the present study was to assess the uptake and metabolism of waterborne pharmaceuticals in rainbow trout (Oncorhynchus mykiss). A further objective was to determine the possibility of monitoring exposure to low levels of pharmaceuticals by bile assays. Rainbow trout were exposed for 10 d under flow-through conditions to mixtures of five pharmaceuticals (diclofenac, naproxen, ibuprofen, bisoprolol, and carbamazepine) at high and low concentrations. The low concentration was used to mimic the conditions prevailing in the vicinity of the discharge points of wastewater treatment plants. The uptake and the bioconcentration were determined by blood plasma and bile analyses. The average bioconcentration factor in plasma ranged from below 0.1 for bisoprolol to 4.9 for diclofenac, the values being approximately similar at low and high ambient concentrations. The biotransformation of diclofenac, naproxen, and ibuprofen was considered efficient, because several metabolites could be detected in concentrations clearly exceeding those of the unmetabolized compounds. The glucuronides were the dominant metabolites for all three pharmaceuticals. The total bioconcentration in the bile was two to four orders of magnitude higher than in the plasma. The results of this work show that the exposure of fish to pharmaceuticals in environmentally relevant concentrations may be monitored by blood plasma and bile analyses, the latter allowing detection at markedly lower ambient concentration.

Does ketoprofen or diclofenac pose the lowest risk to fish?

“…Several studies have reported effects on fish at these concentrations of diclofenac, ranging from cytological and histological effects [14][15][16][17] to effects on gene expression [15,18]. Reported bioconcentration factors (BCFs) for diclofenac in rainbow trout varies between studies [10,11,16,18,19]. However, the most recent studies are in relatively close agreement, showing a stable BCF from water to blood plasma of approximately 4 [18,19].…”

“…Reported bioconcentration factors (BCFs) for diclofenac in rainbow trout varies between studies [10,11,16,18,19]. However, the most recent studies are in relatively close agreement, showing a stable BCF from water to blood plasma of approximately 4 [18,19]. We have recently shown effects on the global hepatic gene expression at exposure concentrations of diclofenac down to 1.6 g/L, even though the corresponding plasma concentration of exposed fish was relatively low (approximately 6 ng/mL) in comparison with the human therapeutic plasma concentrations (HTPC) of >420 ng/mL [20,21].…”

Metabolite profiling of carbamazepine and ibuprofen in Solea senegalensis bile using high-resolution mass spectrometry

“…In addition to the dosing experiments of this marine species with CBZ, bile was harvested and profiled for drug metabolites after administration of IBU. The findings obtained for the marine fish were contrasted with those reported for rainbow trout inhabiting freshwater environments [15,21]. The work presented here was carried out as part of a broader study on the biological interactions of human drugs with hepatic enzymes in fish [22].…”

Pharmaceutical pollution of aquatic environment: an emerging and enormous challenge

“…For example, the popular non-steroidal anti-inflammatory drugs, diclofenac, naproxen and ibuprofen, were all shown to accumulate in fish (Lahti et al 2011). The concentration of ibuprofen determined in the fish plasma and bile samples was 100 to 1000-fold higher than in corresponding water samples (Jeffries et al 2015).…”