Embryotoxicity of fluoxetine (Prozac®) to Japanese medaka

Abstract

Fluoxetine hydrochloride (FLX), Prozac®, is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to patients suffering from depression and other psychiatric disorders. FLX is known to enter the aquatic environment through municipal effluent discharge so that the constant release of this drug into aquatic environments exposes all organisms throughout all stages of development. In the current study, we evaluated the role of FLX in aquatic toxicology by modeling the toxicity of maternally-transferred compounds on fish embryo development using Japanese medaka (Oryzias latipes) as a model species. Three different methods: (1) waterborne exposure, (2) nano-injections and (3) topical application were considered and undertaken to measure the embryotoxicity of FLX. Waterborne exposure and nano-injection presented difficulties in mimicking the transfer of contaminated maternal tissue to embryos; thus, topical application was used as the method of choice. Dosing for toxicity tests was performed by topical application of FLX in dimethylsulfoxide (DMSO) onto the exterior of newly fertilized eggs to transport the chemical into the egg. Toxicity was assessed by observing how it affected mortality and adverse fish development, as indicated by the frequency of signs of pathology in fish embryos. From the results, FLX does cause developmental abnormalities as observed from the significant decrease in the percentage of normal fish. This occurrence is mostly contributed from a high prevalence of body hemorrhaging in comparison to the other signs of pathology. Thus, FLX may be maternally-transferred to oocytes during sexual maturation to cause embryotoxicity.