Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis

Abstract

a b s t r a c tFluoxetine, a selective serotonin re-uptake inhibitor (SSRI) antidepressant, is among the most prescribed pharmaceutical active substances worldwide. This study aimed to assess its accumulation and metabolization in the mussel Mytillus galloprovincialis, considered an excellent sentinel species for traditional and emerging pollutants. Mussels were collected from Ria Formosa Lagoon, Portugal, and exposed to a nominal concentration of fluoxetine (75 ng L À1 ) for 15 days. Approximately 1 g of whole mussel soft tissues was extracted with acetonitrile:formic acid, loaded into an Oasis MCX cartridge, and fluoxetine analysed by liquid chromatography with tandem mass spectrometry (LC-MSn). After 3 days of exposure, fluoxetine was accumulated in 70% of the samples, with a mean of 2.53 ng g À1 dry weight (d.w.) and norfluoxetine was only detected in one sample (10%), at 3.06 ng g À1 d.w. After 7 days of exposure, the accumulation of fluoxetine and norfluoxetine increased up to 80 and 50% respectively, and their mean accumulated levels in mussel tissues were up to 4.43 and 2.85 ng g À1 d.w., respectively. By the end of the exposure period (15 days), both compounds were detected in 100% of the samples (mean of 9.31 and 11.65 ng g À1 d.w., respectively). Statistical analysis revealed significant accumulation differences between the 3rd and 15th day of exposure for fluoxetine, and between the 3rd and 7th against the 15th day of exposure for norfluoxetine. These results suggest that the fluoxetine accumulated in mussel tissues is likely to be metabolised into norfluoxetine with the increase of the time of exposure, giving evidence that at these realistic environmental concentrations, toxic effects of fluoxetine in mussel tissues may occur.

Metabolomic Investigations of the Temporal Effects of Exposure to Pharmaceuticals and Personal Care Products and Their Mixture in the Eastern Oyster (Crassostrea virginica)

“…Interestingly, although their trajectories drastically varied, the mixture and fluoxetine treatments clustered near one another in multivariate space post‐depuration (Figure C, E), possibly because of the probable presence of norfluoxetine, fluoxetine's main biotransformation product. In mussels ( M. galloprovincialis ) exposed to fluoxetine norfluoxetine concentrations exceeded those of fluoxetine after 15 d of exposure (Silva et al ), and norfluoxetine was more prone to bioaccumulate than fluoxetine, although eliciting a similar biological effect (Daughton and Brooks ). Although it is possible that given more time the oysters would be able to recover completely from these exposures in a laboratory setting, it is currently unknown how accurate this prediction would be in the environment, where contaminants are introduced sporadically and for indeterminate durations (Rozman and Doull ).…”

Influence of Selected Antidepressants on the Ciliated Protozoan Spirostomum ambiguum: Toxicity, Bioaccumulation, and Biotransformation Products

“…Chu et al [46] found increased concentrations of norfluoxetine in fish incubated with fluoxetine. The mussel M. galloprovincialis was exposed to a nominal concentration of fluoxetine (75 ng/L) for 15 days [47]. The authors observed that the concentration of fluoxetine and norfluoxetine increased from 2.53 and 3.06 ng/g dry weight after 3 days up to 9.31 and 11.65 ng/g after 15 days, respectively.…”

Early Biological Modulations Resulting from 1-Week Venlafaxine Exposure of Marine Mussels Mytilus galloprovincialis Determined by a Metabolomic Approach

“…In addition, mussels filter large volumes of water and they are known as “suspension feeders”. They filter suspended materials and colloids and they are then known to efficiently bioaccumulate toxic compounds [ 23 , 24 ]. This species is therefore often used as a sentinel organism for the monitoring of coastal water pollution (mussel watch programs) [ 25 ].…”