Biomarkers and antioxidant responses in mussels exposed to fluoxetine, propranolol and their mixture

Pharmaceuticals are molecules designed to produce therapeutic effects at low doses, nevertheless they may provoke side effects after prolonged or high-dose administrations. An increasing number of pharmaceutical residues are found in the aquatic environment, many of which are bioaccumulated by non-target organisms. Two main approaches are followed in our studies on environmental pharmaceuticals and their possible effects on wildlife, a first one concerning the Mode of Action (MOA), to assess whether specific molecular targets are found in mussels as they are in humans, and a second one to evaluate a range of potential side effects. In the present work we addressed our attention to the alteration of physiological parameters related to oxidative stress. The xenobiotic-induced enhancement of reactive oxygen species (ROS) results in oxidative stress when it exceeds antioxidant defense mechanisms in exposed animals. One of the defense mechanisms involves the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). Other enzymes participate to detoxification, for example phase II glutathione S-transferase (GST). In mussels exposed for 7 days to fluoxetine (FX), propranolol (PROP) and their mixture (MIX) at environmental concentrations, we observed significant reduction of lysosome membrane stability and increase in lysosome/cytosol ratio and lipofuscin accumulation. Concomitantly CAT gene expression was decreased in all experimental conditions. SOD and GST gene expressions were decreased after exposure to PROP and MIX, respectively. As to enzyme activities, only small increases were observed in the presence of PROP. Altogether, we hypothesise that detoxification responses are not adequately enhanced to protect mussels from oxidative effects due to pharmaceutical exposure.