Gender and organ responsiveness in Dreissena polymorpha exposed to the antidepressant sertraline: from uptake to effects

Sessile bivalves like Zebra mussels are effective bioindicators of aquatic contaminants due to their ability to bioaccumulate various pollutants. In the aquatic environment, pharmaceuticals like selective serotonin reuptake inhibitor (SSRI) have been reported to exert effect on bioaccumulation, metabolism and physiological functions. In this study, the gender-specific absorption, distribution, and metabolism of sertraline, a toxic SSRI and its effect on physiological functions in the digestive gland and gonad tissues of mussels was evaluated. The findings revealed a clear concentration-dependent accumulation of sertraline, with females exhibiting higher metabolic conversion to its active metabolite, norsertraline, particularly at intermediate doses than males. This suggests a potential sex-specific differences in cytochrome P450 enzyme activity and hormonal influence on drug metabolism. Sertraline exposure disrupted vital physiological processes like filter feeding, energy metabolism and mitochondria function. Interestingly, males showed more pronounced mitochondrial and metabolic disruptions, including a shift from aerobic to anaerobic respiration, and altered energy reserves. Females, while less sensitive, exhibited compensatory metabolic adaptations at higher doses. Hemolymph osmolality decreased significantly in both genders, implying impaired osmoregulation potentially linked to serotonergic pathway disruptions. Moreover, sertraline exposure modulated monoamine oxidase (MAO) activity, reduced total antioxidant capacity (TAC), and altered markers of oxidative stress, inflammation and apoptosis, especially at intermediate to high concentrations. These findings highlight sertraline's potential to induce neurotoxic, immunotoxic, and metabolic stress responses in non-target freshwater organisms, emphasizing the need for further ecotoxicological assessments of SSRIs in aquatic environments.