Acute and chronic effects of paracetamol exposure on Daphnia magna: how oxidative effects may modulate responses at distinct levels of organization in a model species

The modern usage of pharmaceutical drugs has led to a progressive increase in their presence and environment concentrations, particularly in the aquatic compartment which is the most common final dumping location for this specific class of chemicals. These substances, due to their chemical and biological properties, can exert mostly uncharacterized toxic effects to non-target aquatic species, given the diverse pathways they activate, and the large number of putative targets in the wild. Among drugs in the environment, paracetamol assumes a leading role, considering its widespread therapeutic use and consequently, environmental presence. The present study aimed to assess the acute and chronic effects of paracetamol, in ecologically relevant levels, in the freshwater cladoceran Daphnia magna, namely focusing on biochemical and reproductive parameters. Considering the pro-oxidant effects of paracetamol, already described for a large set of aquatic organisms, specific enzymes involved in the anti-oxidant and metabolic responses were quantified, namely catalase (CAT) and glutathione S-transferases (GSTs) activities. Cholinesterases (ChEs) activity was quantified to evaluate the capacity of paracetamol to induce neurotoxicity, an indirect outcome of oxidative effects by paracetamol, that may affect feeding behavior and reproductive outcomes of this crustacean. Paracetamol in the tested levels showed no effect on reproductive traits of D. magna. Results obtained for organisms acutely exposed included significant increases in the activities of both GSTs and CAT, demonstrating a short-term pro-oxidative effect by paracetamol. On the contrary, ChEs activity was significantly decreased in organisms exposed to this drug, showing a possible interference with neurotransmission. On the contrary, no noteworthy effects were reported for organisms chronically exposed to ecologically realistic concentrations, evidencing the transient nature of the obtained biological response. These results demonstrate the responsiveness of D. magna to paracetamol, especially for high levels of exposure that, despite not being environmentally relevant, are able to trigger significant antioxidant responses. No population effects were likely to be caused by realistic levels of paracetamol, and the absence of biochemical changes after chronic exposure suggests that this specific organism may not be deleteriously affected by low levels of paracetamol, under real scenarios of contamination.