Biochemical and cellular biomarkers in brown trout (Salmo trutta f. fario) in response to the antidepressants citalopram and venlafaxine

Abstract

Background During the last decades, a worldwide increase in the number of cases of depression accompanied by rising prescription rates of antidepressants was recorded. In Germany, the two most prescribed antidepressants are the selective serotonin reuptake inhibitor (SSRI) citalopram and the serotonin and noradrenalin reuptake inhibitor (SNRI) venlafaxine, taking about 30% of the market share. Both antidepressants are found frequently in surface waters and have the potential of adversely affecting aquatic organisms. Most studies dealing with antidepressants address apical endpoints and behaviour; however, only few studies investigate biochemical biomarkers and histopathological alterations. We conducted citalopram and venlafaxine exposure experiments over 5 months, starting with brown trout eggs in the eyed-ova stage, as well as with juvenile brown trout for 4 weeks. Exposure concentrations ranged from environmentally relevant 1 µg/L up to 1 mg/L. In this study, we investigated the effects of the antidepressants on b-esterase activity (neurotoxicity), stress protein level (proteotoxicity) and superoxide dismutase activity (oxidative stress). Additionally, we assessed the health status of the liver by means of histopathological analyses. Results We were able to show that both antidepressants did neither induce proteotoxic nor neurotoxic effects in brown trout. But for venlafaxine, the biochemical biomarker for oxidative stress (superoxide dismutase activity) was significantly increased in larvae exposed to at least 10-µg/L venlafaxine at 7 °C. With regard to liver histopathology, fish exposed to higher citalopram concentrations were in a worse health condition than control fish irrespective of their life stage. Also, the energy storage of fish exposed to 1 mg/L citalopram was reduced. Conclusion Thus, we here report citalopram-dependent histopathological alterations in brown trout liver, and the induction of oxidative stress by venlafaxine.

Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)

“…In another invertebrate species, Gammarus locusta, no effect of the antidepressant sertraline on the activity of AChE could be detected either [98]. Similarly, in juvenile meagre and larval and juvenile brown trout, no evidence for any changes in the AChE activity of fish exposed to either venlafaxine or citalopram was found [24,60]. However, in the invertebrate species Manila clam (Venerupis philippinarum) and Daphnia magna, as well as in the fish species common goby (Pomatoschistus microps), decreases in AChE activity have been reported after exposure to 5 mg/L fluoxetine and 1 mg/L citalopram [26,68].…”

“…Such ROS regularly causes oxidative stress in organisms where an imbalance of oxidants and antioxidants prevails [57,58]. Increased SOD activity has been demonstrated in daphnids and fish after exposure to several antidepressants, such as citalopram, venlafaxine, amitriptyline, or sertraline [24,26,55,59,60]. Based on these findings, the potential induction of oxidative stress in snails exposed to citalopram and venlafaxine was assessed in the present study, through the measurement of SOD activity in the hepatopancreas.…”

“…Before the experiment, the snails (>0.7 g ≈ >9 months) were transferred into an acclimation tank at room temperature, which was then placed in a climatic chamber to decrease the temperature gradually to 11 • C. This temperature was chosen because it reflects the temperatures in spring and autumn. In addition, the data were aimed to be comparable with results from earlier experiments conducted in brown trout at 11 C [60]. After one day of acclimation, the snails were transferred into the exposure tanks.…”

“…The aquaria were set up in a 11 • C climatic chamber in a randomised three-block design, with each block comprising the exposure concentrations of 0, 1, 10, 100 and 1000 µg/L of either citalopram or venlafaxine, resulting in three replicate aquaria per treatment. Concentrations were chosen to be comparable with previous publications [60,74,75]. As the number of animals of the same age was limited, we used seven snails per tank in the experiment with venlafaxine, but only five snails per tank in the experiment with citalopram.…”

“…Subsequently, the supernatant was taken up in Tris-HCl buffer (50 mM, pH 8; sample/buffer ratio 1:170 v/v) and frozen at −80 • C until further processing (no longer than 1 month). The assay was performed with duplicate samples, as previously described by Ziegler, et al [60], and enzymatic activity measured photometrically at 450 nm. Each sample was treated as an independent sample, and the mean value of the treatment was calculated from all measured samples from one treatment.…”