Organic chemistry

Enzyme

Hyalella azteca

Biology

Environmental chemistry

Pharmacokinetics

Metabolome

Toxicodynamics

Metabolomics

Chemistry

Ecology

Toxicokinetics

Amphipoda

Diclofenac

Biotransformation

Toxicity

Chromatography

Biochemistry

Bioaccumulation

Crustacean

Pharmacology

Environmental Science & Technology

The exposure of ecologically critical invertebrate species to biologically active pharmaceuticals poses a serious risk to the aquatic ecosystem. Yet, the fate and toxic effects of pharmaceuticals on these nontarget aquatic invertebrates and the underlying mechanisms are poorly studied. Herein, we investigated the toxicokinetic (TK) processes (i.e., uptake, biotransformation, and elimination) of the pharmaceutical diclofenac and its biotransformation in the freshwater invertebrate Hyalella azteca. We further employed mass spectrometry-based metabolomics to assess the toxic effects of diclofenac on the metabolic functions of H. azteca exposed to environmentally relevant concentrations (10 and 100 μg/L). The TK results showed a quick uptake of diclofenac by H. azteca (maximum internal concentration of 1.9 μmol/kg) and rapid formation of the conjugate diclofenac taurine (maximum internal concentration of 80.6 μmol/kg), indicating over 40 times higher accumulation of diclofenac taurine than that of diclofenac in H. azteca. Depuration kinetics demonstrated that the elimination of diclofenac taurine was 64 times slower than diclofenac in H. azteca. Metabolomics results suggested that diclofenac inhibited prostaglandin synthesis and affected the carnitine shuttle pathway at environmentally relevant concentrations. These findings shed light on the significance of the TK process of diclofenac, especially the formation of diclofenac taurine, as well as the sublethal effects of diclofenac on the bulk metabolome of H. azteca. Combining the TK processes and metabolomics provides complementary insights and thus a better mechanistic understanding of the effects of diclofenac in aquatic invertebrates.

Metabolomic Profiling and Toxicokinetics Modeling to Assess the Effects of the Pharmaceutical Diclofenac in the Aquatic Invertebrate <i>Hyalella azteca</i>

Metabolomic Profiling and Toxicokinetics Modeling to Assess the Effects of the Pharmaceutical Diclofenac in the Aquatic Invertebrate Hyalella azteca