Fluoxetine suppresses the immune responses of blood clams by reducing haemocyte viability, disturbing signal transduction and imposing physiological stress

Abstract

The antidepressant fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely prescribed for the treatment of depression and anxiety disorders. Nowadays, measurable quantities of FLX have been frequently detected in the aquatic ecosystems worldwide, which may pose a potential threat to aquatic organisms. Although the impacts of FLX exposure on immune responses are increasingly well documented in mammals, they remain poorly understood in aquatic invertebrates. Therefore, to gain a better understanding of the ecotoxicological effects of FLX, the impacts of waterborne FLX exposure on the immune responses of blood clam, Tegillarca granosa, were investigated in this study. Results obtained showed that both cellular and humoural immune responses in T. granosa were suppressed by exposure to waterborne FLX, as indicated by total counts of haemocytes (THC), phagocytic rate, and activities of superoxide dismutases (SOD) and catalase (CAT), suggesting that waterborne FLX renders blood clams more vulnerable to pathogen challenges. To ascertain the mechanisms explaining how waterborne FLX affects immune responses, haemocyte viabilities, intracellular Ca²⁺ levels, in vivo concentrations of neurotransmitters, physiological stress conditions (as indicated by in vivo concentrations of cortisol), and expressions of key regulatory genes from Ca²⁺ and neurotransmitter signal transduction, as well as immune-related signalling pathways, were examined after 10 days of FLX exposure by blood clams via 1, 10 and 100 μg/L waterborne FLX. The results obtained indicated that immune response suppression caused by waterborne FLX could be due to (i) inhibited haemocyte viabilities, which subsequently reduce the THC; (ii) altered intracellular Ca²⁺ and neurotransmitter concentrations, which lead to constrained phagocytosis; and (iii) aggravated physiological stress, which thereafter hampers immune-related NFκB signalling pathways.

Keywords: Ca(2+) concentration; Fluoxetine; Immune responses; Neurotransmitters; Stress.