Influence of dissolved organic matter on the accumulation, metabolite production and multi-biological effects of environmentally relevant fluoxetine in crucian carp (Carassius auratus)

Effects of fluoxetine on fish: What do we know and where should we focus our efforts in the future?

“…In water, fluoxetine may be hydrolyzed and suffer photolysis (Kwon and Armbrust, 2006), having a reported half-life of 1 to 4 days, whereas its metabolite norfluoxetine has a higher half-life, of 7 to 15 days (Hiemke and Härtter, 2000). While the reported levels of fluoxetine found in the environment do not induce lethal effects (Farias et al, 2019;Mole and Brooks, 2019), many recent studies have reported that environmentally relevant concentrations can change ecologically important traits in fish species (Dorelle et al, 2020;Duarte et al, 2019;Duarte et al, 2020;Farias et al, 2020;Farias et al, 2019;Parolini et al, 2019;Pelli and Connaughton, 2015;Pittman and Hylton, 2015;Theodoridi et al, 2017;Weinberger and Klaper, 2014;Winder et al, 2012;Yan et al, 2020).…”

“…2018) reported accumulation of fluoxetine in D. rerio embryos body and the brain, liver, and muscle of adult Carassius auratus, with higher levels of bioaccumulation found after exposure to 0.1 μg/L fluoxetine, after 120 h (BCF embryos = 6.88) and 30 days of exposure (BCF brain = 110; BCF liver = 137; BCF muscle = 166), respectively. Using C. auratus juveniles, Yan et al (2020) detected fluoxetine and its active metabolite (norfluoxetine) in the liver, brain, gill, bile, and kidney of organisms exposed for 7 and 14 days to concentrations as low as 0.1 μg/L, with detected concentrations increasing with exposure duration. Fluoxetine was detected at higher levels in the brain (demonstrating its ability to cross the blood-brain barrier) and liver (one of the main sites of metabolic activity) (Brooks et al, 2005;Dorelle et al, 2020;Yan et al, 2020).…”

“…Using C. auratus juveniles, Yan et al (2020) detected fluoxetine and its active metabolite (norfluoxetine) in the liver, brain, gill, bile, and kidney of organisms exposed for 7 and 14 days to concentrations as low as 0.1 μg/L, with detected concentrations increasing with exposure duration. Fluoxetine was detected at higher levels in the brain (demonstrating its ability to cross the blood-brain barrier) and liver (one of the main sites of metabolic activity) (Brooks et al, 2005;Dorelle et al, 2020;Yan et al, 2020). The accumulation of fluoxetine and norfluoxetine in the brain and liver may be attributed to the abundant content of lipids and proteins in these tissues, to which fluoxetine can bind (Grabicova et al, 2017;Grabicova et al, 2014;Nichols et al, 2015) and lead to significant changes in the expression of genes associated with brain processes of serotonergic and cholinergic neurotransmission.…”

Chronic Effects of Fluoxetine on Danio rerio: A Biochemical and Behavioral Perspective

“…The effects of fluoxetine on antioxidant responses and biotransformation processes have been widely reported, with increased or decreased activity of enzymes belonging to these groups (CAT, SOD, GSH/GSSH, LPO/MDA, GST, and EROD activity). The different fluoxetine concentrations tested, exposure lengths, species, and life stages tested may be related to the variability of responses [40][41][42][43][44]46]. However, all these studies evidence and support the potential of fluoxetine to promote long-term biochemical effects.…”

“…In the freshwater environment, concentrations of fluoxetine have been detected at levels ranging from 0.0004 to 3.645 µg/L in wastewater treatment plants (WWTP) [20][21][22][23][24][25][26][27][28][29][30][31], 0.0005 to 0.056 µg/L in surface waters and groundwaters [29,[31][32][33][34][35][36][37] and, for drinking water, the levels vary between 0.0005 and 0.0008 µg/L [38,39]. Previous studies have demonstrated that fluoxetine can be toxic to fish, with exposure resulting in changes at different biological levels, from gene transcription, neurotransmission markers, enzymatic activities (e.g., oxidative stress, metabolism), hormone levels, reproductive processes, and accumulation in various tissues (e.g., brain and liver), resulting in a severe change in the histology of these organs [4][5][6][7]10,11,14,[40][41][42][43][44][45][46][47][48]. In addition, this pharmaceutical can cause changes in behavior (e.g., locomotor activity, stress response, feeding, aggression, social and anti-predatory behavior) [4][5][6][7]…”