Short-term effects of neuroactive pharmaceutical drugs on a fish species: Biochemical and behavioural effects

Brandão, Fátima; Rodrigues, Sara; Castro, Bruno B.; Gonçalves, Fernando; Antunes, Sara C.; Nunes, Bruno

doi:10.1016/j.aquatox.2013.10.005

Cited by 112 publications

(44 citation statements)

References 81 publications

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“…The consequence of increased GR activity is more intensive reduction of the oxidised form of glutathione. Our findings are in concordance with Brandao et al (2013), who found that exposure to CBZ caused an increase in GST and GR activity in pumpkinseed sunfish (Lepomis gibbosus), as well as with the findings of Li et al (2011), who reported a significant increase in GR activity in rainbow trout (Oncorhynchus mykiss) exposed to CBZ for 96 h.…”

Section: Discussionsupporting

confidence: 82%

“…In fact, we expected CBZ to exhibit pro-oxidant behaviour on the basis of the results of Tsiaka et al (2013) and Li et al (2011), who found that exposure to CBZ resulted in increased lipid peroxidation in the unicellular marine algal species Dunaliella tertiolecta, haemocytes of the mussel Mytilus galloprovincialis, and rainbow trout. Brandao et al (2013) found no changes in lipid peroxidation levels in pumpkinseed sunfish after CBZ exposure. An important factor which should be taken into account is the tested concentration used.…”

Section: Discussionmentioning

confidence: 85%

“…Carbamazepine is an anticonvulsant drug, indicated for epilepsy, mood stabilisation in bipolar disorder, and it is also effective in the treatment of neuropathic pain. It acts in the central nervous system by blocking voltage-dependent sodium channels of excitatory neurons (Brandao et al 2013). Our results show that CBZ did not have any impact on most of the antioxidant enzymes which were investigated, except for an increased activity of GR ( Figures 1A-D).…”

Section: Discussionmentioning

confidence: 99%

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Effects of the pharmaceutical contaminants ibuprofen, diclofenac, and carbamazepine alone, and in combination, on oxidative stress parameters in early life stages of tench (Tinca tinca)

Stancová¹,

Plhalová²,

Blahová³

et al. 2017

Vet. Med. - Czech

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ABSTRACT:In the present study, the effects of sub-lethal sub-chronic doses of ibuprofen, diclofenac, and carbamazepine alone, and in combination (concentration range 0.02-60 µg/l), on the early life stages of tench (Tinca tinca) were investigated. The lower concentrations of pharmaceuticals tested (0.02, 0.2, 2 µg/l) represent the concentration values of these substances commonly present in surface waters or effluents from wastewater treatment plants. Multiple biomarkers of biotransformation, antioxidant defence systems, and lipid peroxidation were determined in fish after 35 days of exposure. The evaluated pharmaceuticals induced oxidative stress in fish both alone and in combination with each other. Generally, 60 µg/l of each single pharmaceutical influenced the activity of antioxidant enzymes significantly (P < 0.05), whereas the same concentration of these pharmaceuticals in combination (1 : 1 : 1) did not have any impact on the activity of these enzymes. However, changes in biotransformation and antioxidant enzymes were apparent if lower concentrations of these pharmaceuticals were administered in the mixture. Significant changes (P < 0.05) in the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were observed even at environmental concentration ranges. A significant effect (P < 0.05) on lipid peroxidation levels was found only in the experimental group exposed to carbamazepine. Keywords: antioxidant defence system; lipid peroxidationList of abbreviations ANC = acid-neutralising capacity, CAT = catalase, CBZ = carbamazepine, COD Mn = chemical oxygen demand, COX = cyclooxygenase, DCF = diclofenac, DMSO = dimethylsulfoxide, GPx = glutathione peroxidase, GR = glutathione reductase, GSH = reduced active form of glutathione, GSSG = oxidised inactive form of glutathione, GST = glutathione-S-transferase, IBU = ibuprofen, LC = liquid chromatography, LC-MS/MS = liquid chromatography with tandem mass spectrometry, LPO = lipid peroxidation level, NSAIDs = non-steroidal anti-inflammatory drugs, ROS = reactive oxygen species Pharmaceutical mixtures that contaminate water sources are currently a problem worldwide. Ibuprofen (IBU), diclofenac (DCF), and carbamazepine (CBZ) are among the most frequently detected drugs in aquatic ecosystems. Their concentrations in surface water range from ng/l to tens of µg/l. Higher concentrations have been detected in developing countries due to the direct discharge of untreated wastewater from residences and hospitals into surface waters (Tran et al. 2014).

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Effects of the pharmaceutical contaminants ibuprofen, diclofenac, and carbamazepine alone, and in combination, on oxidative stress parameters in early life stages of tench (Tinca tinca)

Stancová¹,

Plhalová²,

Blahová³

et al. 2017

Vet. Med. - Czech

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“…Benzodiazepines depress the central nervous system, and are used to treat anxiety, insomnia and muscle spasms [69]. One of the most commonly used benzodiazepines, diazepam, has been shown to increase activity in zebrafish [55] and pumpkinseed sunfish [57] at mg l 21 concentrations, and exposure to mg l 21 diazepam increased boldness in larval zebrafish [56] (table 2). Similar effects, that is, increased activity and affinity towards light, were shown for zebrafish exposed to three benzodiazepines [54] (table 2).…”

Section: (B) Pharmaceutical Effects On Fish Behaviour (I) Antidepressmentioning

confidence: 99%

Ecological effects of pharmaceuticals in aquatic systems—impacts through behavioural alterations

Brodin

Piovano

Fick

et al. 2014

Phil. Trans. R. Soc. B

381

243

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The study of animal behaviour is important for both ecology and ecotoxicology, yet research in these two fields is currently developing independently. Here, we synthesize the available knowledge on drug-induced behavioural alterations in fish, discuss potential ecological consequences and report results from an experiment in which we quantify both uptake and behavioural impact of a psychiatric drug on a predatory fish ( Perca fluviatilis ) and its invertebrate prey ( Coenagrion hastulatum ). We show that perch became more active while damselfly behaviour was unaffected, illustrating that behavioural effects of pharmaceuticals can differ between species. Furthermore, we demonstrate that prey consumption can be an important exposure route as on average 46% of the pharmaceutical in ingested prey accumulated in the predator. This suggests that investigations of exposure through bioconcentration, where trophic interactions and subsequent bioaccumulation of exposed individuals are ignored, underestimate exposure. Wildlife may therefore be exposed to higher levels of behaviourally altering pharmaceuticals than predictions based on commonly used exposure assays and pharmaceutical concentrations found in environmental monitoring programmes.

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“…R. Soc. B 369: 20140022 [24,27,30,31] anti-androgens androgen receptor antagonism -impaired ovulation and spawning -impaired sexual differentiation -decreased nest defence -reproductive impairment -reduced probability of young of year survival** [32 -37] hormonal contraceptive oestrogen receptor activation -impaired ovulation and spawning -impaired sexual development -reproductive impairment [27] hormonal contraceptive oestrogen receptor antagonism* -impaired vitellogenesis, ovulation and spawning -impaired sexual differentiation -reproductive impairment** [38 -42] hormonal contraceptive progesterone receptor activation -reduced fecundity -reduced sperm motility -reproductive impairment [43 -46] anti-inflammatory glucocorticoid receptor activation -reduced oestradiol synthesis and fecundity -morphological abnormalities -decreased immune response -reproductive impairment -reduced probability of young of year survival** [47 -49] anti-depressants serotonin reuptake inhibition -morphological abnormalities -reduced fecundity -decreased food intake -impaired predator avoidance -reproductive impairment -reduced probability of young of year survival** [50 -55] anti-convulsant gamma-aminobutyric-acid receptor opening** sodium-channel inhibition -impaired predator avoidance -reduced probability of young of year survival** [56,57] non-steroidal anti-inflammatory drugs cyclooxygenase inhibition -impaired growth -impaired hatching -decreased spawning behaviour a -reduced fecundity a -increased probability of mortality** -reduced probability of young of year survival** -impaired reproduction a [58 -60] fibrates peroxisome proliferator-activated receptor activation -reduced fecundity -impaired reproduction [61] beta-blockers beta-adrenergic receptor antagonist -reduced growth -reduced probability of young of year survival** -increased probability of mortality** [62 -64] Aromatase inhibition is an established molecular initiating event for propiconazole, however other conazoles have been shown to inhibit other cytochrome P450 enzymes [76].…”

Section: (B) Conservation Of Molecular Target For Cross-species Extramentioning

confidence: 99%

Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms

LaLone

Berninger

Villeneuve

et al. 2014

Phil. Trans. R. Soc. B

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Medicinal innovation has led to the discovery and use of thousands of human and veterinary drugs. With this comes the potential for unintended effects on non-target organisms exposed to pharmaceuticals inevitably entering the environment. The impracticality of generating whole-organism chronic toxicity data representative of all species in the environment has necessitated prioritization of drugs for focused empirical testing as well as field monitoring. Current prioritization strategies typically emphasize likelihood for exposure (i.e. predicted/measured environmental concentrations), while incorporating only rather limited consideration of potential effects of the drug to non-target organisms. However, substantial mammalian pharmacokinetic and mechanism/mode of action (MOA) data are produced during drug development to understand drug target specificity and efficacy for intended consumers. An integrated prioritization strategy for assessing risks of human and veterinary drugs would leverage available pharmacokinetic and toxicokinetic data for evaluation of the potential for adverse effects to non-target organisms. In this reiview, we demonstrate the utility of read-across approaches to leverage mammalian absorption, distribution, metabolism and elimination data; analyse cross-species molecular target conservation and translate therapeutic MOA to an adverse outcome pathway(s) relevant to aquatic organisms as a means to inform prioritization of drugs for focused toxicity testing and environmental monitoring.

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Short-term effects of neuroactive pharmaceutical drugs on a fish species: Biochemical and behavioural effects

Cited by 112 publications

References 81 publications

Effects of the pharmaceutical contaminants ibuprofen, diclofenac, and carbamazepine alone, and in combination, on oxidative stress parameters in early life stages of tench (Tinca tinca)

Effects of the pharmaceutical contaminants ibuprofen, diclofenac, and carbamazepine alone, and in combination, on oxidative stress parameters in early life stages of tench (Tinca tinca)

Ecological effects of pharmaceuticals in aquatic systems—impacts through behavioural alterations

Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms

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