Molecular Responses of Daphnids to Chronic Exposures to Pharmaceuticals

Pharmaceutical compounds are among several classes of contaminants of emerging concern, such as pesticides, heavy metals and personal care products, all of which are a major concern for aquatic ecosystems. The hazards posed by the presence of pharmaceutical is one which affects both freshwater organisms and human health—via non-target effects and by the contamination of drinking water sources. The molecular and phenotypic alterations of five pharmaceuticals which are commonly present in the aquatic environment were explored in daphnids under chronic exposures. Markers of physiology such as enzyme activities were combined with metabolic perturbations to assess the impact of metformin, diclofenac, gabapentin, carbamazepine and gemfibrozil on daphnids. Enzyme activity of markers of physiology included phosphatases, lipase, peptidase, β-galactosidase, lactate dehydrogenase, glutathione-S-transferase and glutathione reductase activities. Furthermore, targeted LC-MS/MS analysis focusing on glycolysis, the pentose phosphate pathway and the TCA cycle intermediates was performed to assess metabolic alterations. Exposure to pharmaceuticals resulted in the changes in activity for several enzymes of metabolism and the detoxification enzyme glutathione-S-transferase. Metabolic perturbations on key pathways revealed distinct groups and metabolic fingerprints for the different exposures and their mixtures. Chronic exposure to pharmaceuticals at low concentrations revealed significant alterations of metabolic and physiological endpoints.