Multiple Stressors in the Environment: The Effects of Exposure to an Antidepressant (Venlafaxine) and Increased Temperature on Zebrafish Metabolism

Abstract

Aquatic organisms are continuously exposed to multiple environmental stressors working cumulatively to alter ecosystems. Wastewater-dominated environments are often riddled by a myriad of stressors, such as chemical and thermal stressors. The objective of this study was to examine the effects of an environmentally relevant concentration of a commonly prescribed antidepressant, venlafaxine (VFX) [1.0 μg/L], in addition to a 5°C increase in water temperature on zebrafish metabolism. Fish were chronically exposed (21 days) to one of four conditions: (i) 0 μg/L VFX at 27°C; (ii) 1.0 μg/L VFX at 27°C; (iii) 0 μg/L VFX at 32°C; (iv) 1.0 μg/L VFX at 32°C. Following exposure, whole-body metabolism was assessed by routine metabolic rate (RMR) measurements, whereas tissue-specific metabolism was assessed by measuring the activities of major metabolic enzymes in addition to glucose levels in muscle. RMR was significantly higher in the multi-stressed group relative to Control. The combination of both stressors resulted in elevated pyruvate kinase activity and glucose levels, while lipid metabolism was depressed, as measured by 3-hydroxyacyl CoA dehydrogenase activity. Citrate synthase activity increased with the onset of temperature, but only in the group treatment without VFX. Catalase activity was also elevated with the onset of the temperature stressor, however, that was not the case for the multi-stressed group, potentially indicating a deleterious effect of VFX on the anti-oxidant defense mechanism. The results of this study highlight the importance of multiple-stressor research, as it able to further bridge the gap between field and laboratory studies, as well as have the potential of yielding surprising results that may have not been predicted using a conventional single-stressor approach.

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

“…Generally, with climate change in mind, temperature plays an important role in our scenarios, because it can have an impact on many physiological responses in fish [77,[79][80][81]. We could see that fish exposed at 11 °C revealed an overall higher SOD activity; however, differences between larvae exposed at 11 °C and 7 °C cannot solely be attributed to temperature effects, because of different exposure times.…”

“…Elevated oxidative stress indicated by changes in catalase, peroxidase, glutathione-S-transferase (GST) and SOD activity has been shown in meagre exposed to venlafaxine [28], zebrafish exposed to amitriptyline [31], goldfish exposed to sertraline [30] and daphnids exposed to citalopram [42]. In a multi-stressor experiment, temperature effects on the anti-oxidant defence have been shown and potential deleterious effects of venlafaxine on the anti-oxidant defence mechanism of zebrafish were indicated [81]. However, in one study, fluoxetine-exposed Pomatoschistus microps did not show a change in SOD activity [82].…”

Biochemical and Cellular Biomarkers in Brown Trout (Salmo trutta f. fario) in Response to the Antidepressants Citalopram and Venlafaxine

“…Generally, temperature plays an important role in our scenarios, because it can have an impact on many physiological responses in sh (35,38,42,68). We could see that sh exposed at 11 °C revealed an overall higher SOD-activity, however, differences between larvae exposed at 11 °C and 7 °C cannot solely be attributed to temperature effects, because of different exposure times.…”

“…Elevated oxidative stress indicated by changes in catalase, peroxidase, glutathione-S-transferase (GST) and SOD-activity have been shown in meagre exposed to venlafaxine (41), zebra sh exposed to amitriptyline (73), gold sh exposed to sertraline (71) and daphnids exposed to citalopram (72). In a multi stressor experiment temperature effects on the anti-oxidant defence have been shown and potential deleterious effects of venlafaxine on the antioxidant defence mechanism of zebra sh were indicated (42). However, in one study, uoxetine-exposed Pomatoschistus microps did not show a change in SOD activity (12).…”

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

“…For both antidepressants, adverse effects in aquatic organisms have been observed, with the majority of studies addressing behavioural effects in fish [15][16][17][18][19][20][21][22][23]. Regarding biochemical or histological endpoints, only a couple of studies have been conducted [24][25][26][27]. Furthermore, few data are available regarding their effects on aquatic invertebrates [26,[28][29][30][31][32].…”