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

Abstract

The widespread occurrence of pharmaceuticals in the aquatic environment has raised concerns about potential adverse effects on exposed wildlife. Very little is currently known on exposure levels and clearance mechanisms of drugs in marine fish. Within this context, our research was focused on the identification of main metabolic reactions, generated metabolites, and caused effects after exposure of fish to carbamazepine (CBZ) and ibuprofen (IBU). To this end, juveniles of Solea senegalensis acclimated to two temperature regimes of 15 and 20°C for 60 days received a single intraperitoneal dose of these drugs. A control group was administered the vehicle (sunflower oil). Bile samples were analyzed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry on a Q Exactive (Orbitrap) system, allowing to propose plausible identities for 11 metabolites of CBZ and 13 metabolites of IBU in fish bile. In case of CBZ metabolites originated from aromatic and benzylic hydroxylation, epoxidation, and ensuing O-glucuronidation, O-methylation of a catechol-like metabolite was also postulated. Ibuprofen, in turn, formed multiple hydroxyl metabolites, Oglucuronides, and (hydroxyl)-acyl glucuronides, in addition to several taurine conjugates. Enzymatic responses after drug exposures revealed a water temperature-dependent induction of microsomal carboxylesterases. The metabolite profiling in fish bile provides an important tool for pharmaceutical exposure assessment.

Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses

“…Interestingly, we were able to detect a second bioTP of CBZ, CBZ-DH, through analysis of the exposure medium. CBZ-DH is formed from CBZ-Ep, facilitated by soluble epoxide hydrolase (sEH) enzymes, and has been previously reported to form in fish. , One of these studies found sEH in high quantities in the liver, kidney, and gills of rainbow trout (Salmo gairdneri). The discrepancy in CBZ-DH formation could indicate that epoxide hydrolase activity is low or nonpresent in liver microsome extracts, possibly through sEH inactivation during the preparation of the microsome extract because CBZ-DH is predominantly biotransformed in the gills, kidneys, or a combination of the two.…”

Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation

“…(Data not shown). Moreover, these degraded products are expected to further accumulate in water bodies via biotic and abiotic mechanisms (Aceña et al, 2017). Thus, the implications discussed in this work, degradation and toxicological effects, are transferable to the environmentally-relevant conditions.…”

Behavioural and Biochemical Responses of the Sea Snail Tritia Reticulata to Lithium Concentration Gradient

“…Regarding biotransformation enzymes, glutathione S-transferases (GSTs) are Phase II enzymes known to be involved in xenobiotic detoxification by catalysing hydrophobic and electrophilic molecules when conjugated with glutathione, making them less toxic and thus more easily eliminated (Allocati et al, 2018). Carboxylesterases (CEs) are Phase I hydrolytic enzymes well-known for pesticide detoxification and the metabolic transformation of some pharmaceutical drugs (Acena et al, 2017;Solé et al, 2018). In the present study, no significant differences were observable between the activity of biotransformation enzymes of contaminated and non-contaminated organisms, highlighting the absence of a response of T. reticulata to Li.…”