Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 307
Filter
1.
Chemosphere ; 357: 142026, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615959

ABSTRACT

The consumption of antidepressants, such as fluoxetine, has increased over the years and, as a result, they are increasingly found in aquatic systems. Given the increasing use of zebrafish as an animal model in toxicological studies, this work proposed to evaluate the effects of chronic exposure, for 21 days, to fluoxetine at environmentally relevant concentrations (1, 10, 100, and 1000 ng/L). The behavioral tests performed did not reveal significant effects of fluoxetine. However, oxidative stress and changes in energy metabolism were detected after exposure to the highest concentrations of fluoxetine tested, namely a decrease in glutathione S-transferase (GST) activity (decrease of ca. 31%), increase in catalase (CAT) activity (increase of ca. 71%), and decrease in lactate dehydrogenase (LDH) activity (decrease of ca. 53%). Analysis of the fatty acid profile (FA) revealed a decrease in the omega-3 FA, docosahexaenoic acid (DHA), C22:6 (decrease in relative abundance between 6% and 8% for both the head and body), an increase in omega-6 FA, linoleic acid (LA), C18:2, (increased relative abundance between 8% and 11% in the head and between 5% and 9% in the body), which may suggest changes in the inflammatory state of these organisms. The integrated analysis adopted proved to be useful in detecting subindividual effects of fluoxetine and modes of action in fish.


Subject(s)
Behavior, Animal , Fatty Acids , Fluoxetine , Oxidative Stress , Water Pollutants, Chemical , Zebrafish , Fluoxetine/toxicity , Animals , Water Pollutants, Chemical/toxicity , Behavior, Animal/drug effects , Oxidative Stress/drug effects , Fatty Acids/metabolism , Glutathione Transferase/metabolism , Catalase/metabolism
2.
Aquat Toxicol ; 271: 106924, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38678909

ABSTRACT

The effects of fluoxetine (antidepressant) and ketoprofen (analgesic) on aquatic ecosystems are largely unknown, particularly as a mixture. This work aimed at determining the effect of sublethal concentrations of both compounds individually (0.050 mg/L) and their mixture (0.025 mg/L each) on aquatic communities at a microcosm scale for a period of 14 d. Several physicochemical parameters were monitored to estimate functional alterations in the ecosystem, while model organisms (Daphnia magna, Lemna sp., Raphidocelis subcapitata) and the sequencing of 16S/18S rRNA genes permitted to determine effects on specific populations and changes in community composition, respectively. Disturbances were more clearly observed after 14 d, and overall, the microcosms containing fluoxetine (alone or in combination with ketoprofen) produced larger alterations on most physicochemical and biological variables, compared to the microcosm containing only ketoprofen, which suffered less severe changes. Differences in nitrogen species suggest alterations in the N-cycle due to the presence of fluoxetine; similarly, all pharmaceutical-containing systems decreased the brood rate of D. magna, while individual compounds inhibited the growth of Lemna sp. No clear trends were observed regarding R. subcapitata, as indirectly determined by chlorophyll quantification. The structure of micro-eukaryotic communities was altered in the fluoxetine-containing systems, whereas the structure of bacterial communities was affected to a greater extent by the mixture. The disruptions to the equilibrium of the microcosm demonstrate the ecological risk these compounds pose to aquatic ecosystems.


Subject(s)
Fluoxetine , Ketoprofen , Water Pollutants, Chemical , Fluoxetine/toxicity , Ketoprofen/toxicity , Animals , Water Pollutants, Chemical/toxicity , Ecosystem , Daphnia/drug effects , Araceae/drug effects
3.
J Hazard Mater ; 470: 134179, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38565011

ABSTRACT

Microplastics (MPs) and fluoxetine are ubiquitous emerging pollutants in aquatic environments that may interact with each other due to the carrier effects of MPs, posing unpredictable risks to non-target organisms. However, limited studies have focused on the carrier effects of MPs in the aquatic food chain. This study evaluated the influences of polystyrene MPs on the trophic transfer and biotoxicity of fluoxetine in a simple food chain composed of brine shrimp (Artemia nauplii) and zebrafish (Danio rerio). The finding reveals that carrier effects of MPs enhanced the accumulation of waterborne fluoxetine in brine shrimp, but suppressed that in zebrafish due to the distinct retention times. The accumulated fluoxetine in shrimp was further transferred to fish through the food chain, which was alleviated by MPs due to their cleaning effects. In addition, the specific neurotransmission biotoxicity in fish induced by fluoxetine was mitigated by MPs, whilst the oxidative damage, apoptosis, and immune responses in zebrafish were reversely enhanced by MPs due to the stimulating effect. These findings highlight the alleviating effects of MPs on the trophic transfer and specific biotoxicity of fluoxetine in the food chain, providing new insights into the carrier effects of MPs in aquatic environments in the context of increasing global MP pollution.


Subject(s)
Artemia , Fluoxetine , Food Chain , Microplastics , Polystyrenes , Water Pollutants, Chemical , Zebrafish , Animals , Fluoxetine/toxicity , Microplastics/toxicity , Water Pollutants, Chemical/toxicity , Polystyrenes/toxicity , Artemia/drug effects
4.
Sci Total Environ ; 926: 172146, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38569963

ABSTRACT

Anthropogenic activities have led to the emergence of pharmaceutical pollution in marine ecosystems, posing a significant threat to biodiversity in conjunction with global climate change. While the ecotoxicity of human drugs on aquatic organisms is increasingly recognized, their interactions with environmental factors, such as temperature, remain understudied. This research investigates the physiological effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on two diatom species, Phaeodactylum tricornutum and Thalassiosira weissflogii. Results demonstrate that fluoxetine significantly reduces growth rate and biomass production, concurrently affecting pigment contents and the thermal performance curve (TPC) of the diatoms. Fluoxetine reduces the synthesis of chlorophyll a (Chl a) and carotenoid (Car), indicating inhibition of photosynthesis and photoprotection. Furthermore, fluoxetine decreases the maximum growth rate (µmax) while increasing the optimum temperature (Topt) in both species, suggesting an altered thermal plasticity. This shift is attributed to the observed decrease in the inhibition rate of fluoxetine with rising temperatures. These findings emphasize the physiological impacts and ecological implications of fluoxetine on phytoplankton and underscore the significance of considering interactions between multiple environmental drivers when accessing the ecotoxicity of potential pollutants. The present study provides insights into crucial considerations for evaluating the impacts of pharmaceutical pollution on marine primary producers.


Subject(s)
Diatoms , Humans , Diatoms/physiology , Chlorophyll A , Fluoxetine/toxicity , Temperature , Ecosystem , Pharmaceutical Preparations
5.
Sci Total Environ ; 926: 171802, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38508265

ABSTRACT

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 µg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin-leucine-arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.


Subject(s)
Microcystis , Sertraline , Humans , Sertraline/toxicity , Fluoxetine/toxicity , Selective Serotonin Reuptake Inhibitors/toxicity , Ecosystem , Antidepressive Agents , Gene Expression Profiling , Microcystins/metabolism
6.
Environ Sci Pollut Res Int ; 31(19): 27988-28006, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38528217

ABSTRACT

The antidepressant effect of zinc on mammals has been documented in recent decades, and the concentration of the antidepressant fluoxetine (FLX) in aquatic environments has been rising constantly. The aim of the present study is to evaluate the combined toxicity of a serotonin reuptake inhibitor (FLX) and Zn2+ on a non-target aquatic model organism Daphnia magna. Animals were exposed to single and binary combinations of FLX (20.5 and 41 µg/L for subchronic and 41 and 82 µg/L for acute exposures) and Zn2+ (40 µg/L for subchronic and 80 µg/L for acute exposures). In vivo experiments were done for 7 days subchronic and 48 h acute exposure, while subcellular supernatants of whole Daphnia lysate (WDL) were directly treated with the same concentrations used in the acute experiments. Morphological characteristics, Ca2+-ATPase, antioxidant enzyme activities, and lipid peroxidation were examined. There was antioxidant system suppression and Ca2+-ATPase inhibition despite the diverse response patterns due to duration, concentration, and toxicant type. After acute exposure, biomarkers showed a diminishing trend compared to subchronic exposure. According to integrated biomarker response index (IBR) analysis, in vivo Zn2+ exposure was reasonably effective on the health of D. magna, whereas exposure of WDL to Zn2+ had a lesser impact. FLX toxicity increased in a concentration-dependent manner, reversed by the combined exposure. We concluded that potential pro-oxidative and adverse Ca2+-ATPase effects of FLX and Zn2+ in D. magna may also have harmful impact on ecosystem levels. Pharmaceutical exposure (FLX) should be considered along with their potential to interact with other toxicants in aquatic biota.


Subject(s)
Biomarkers , Daphnia , Fluoxetine , Water Pollutants, Chemical , Zinc , Animals , Daphnia/drug effects , Fluoxetine/toxicity , Biomarkers/metabolism , Water Pollutants, Chemical/toxicity , Antioxidants , Lipid Peroxidation/drug effects , Daphnia magna
7.
Environ Sci Pollut Res Int ; 31(8): 12406-12421, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38233708

ABSTRACT

There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an understanding of whether antidepressants with similar modes of action have consistent negative impacts. Here, we tested the effect of acute exposure to two antidepressants, fluoxetine and venlafaxine (0-50 µg/L), on the behavior of non-target organism, i.e., freshwater pond snail, Lymnaea stagnalis. As compounds interact with chemical cues in the aquatic ecosystems, we also tested whether the effects altered in the presence of bile extract containing 5α-cyprinol sulfate (5α-CPS), a characterized kairomone of a natural predator, common carp (Cyprinus carpio). Behavior was studied using automated tracking and analysis of various locomotion parameters of L. stagnalis. Our results suggest that there are differences in the effects on locomotion upon exposure to venlafaxine and fluoxetine. We found strong evidence for a non-monotonic dose response on venlafaxine exposure, whereas fluoxetine only showed weak evidence of altered locomotion for a specific concentration. Combined exposure to compounds and 5α-CPS reduced the intensity of effects observed in the absence of 5α-CPS, possibly due to reduced bioavailability of the compounds. The results highlight the need for acknowledging different mechanisms of action among antidepressants while investigating their environmental risks. In addition, our results underline the importance of reporting non-significant effects and acknowledging individual variation in behavior for environmental risk assessment.


Subject(s)
Carps , Water Pollutants, Chemical , Animals , Lymnaea , Fluoxetine/toxicity , Venlafaxine Hydrochloride/pharmacology , Ecosystem , Antidepressive Agents/pharmacology , Snails , Aquatic Organisms , Locomotion , Fresh Water , Water Pollutants, Chemical/toxicity
8.
Toxicol Appl Pharmacol ; 483: 116805, 2024 02.
Article in English | MEDLINE | ID: mdl-38191078

ABSTRACT

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.


Subject(s)
Fluoxetine , Lactation , Humans , Female , Child , Rats , Animals , Adult , Fluoxetine/toxicity , Milk, Human , Antidepressive Agents/pharmacology , Body Weight
9.
Environ Int ; 184: 108434, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38237506

ABSTRACT

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.


Subject(s)
Fluoxetine , Terfenadine/analogs & derivatives , Water Pollutants, Chemical , Fluoxetine/toxicity , Water Pollutants, Chemical/analysis , Environmental Monitoring , Antidepressive Agents , Histamine Antagonists , Diphenhydramine , Risk Assessment , Rivers , Pharmaceutical Preparations
10.
Chemosphere ; 349: 140706, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37992907

ABSTRACT

The antidepressant fluoxetine is frequently detected in aquatic ecosystems, yet the effects on aquatic communities and ecosystems are still largely unknown. Therefore the aim of this study is to assess the effects of the long-term application of fluoxetine on key components of aquatic ecosystems including macroinvertebrate-, zooplankton-, phytoplankton- and microbial communities and organic matter decomposition by using traditional and non-traditional assessment methods. For this, we exposed 18 outdoor mesocosms (water volume of 1530 L and 10 cm of sediment) to five different concentrations of fluoxetine (0.2, 2, 20 and 200 µg/L) for eight weeks, followed by an eight-week recovery period. We quantified population and community effects by morphological identification, environmental DNA metabarcoding, in vitro and in vivo bioassays and measured organic matter decomposition as a measure of ecosystem functioning. We found effects of fluoxetine on bacterial, algal, zooplankton and macroinvertebrate communities and decomposition rates, mainly for the highest (200 µg/L) treatment. Treatment-related decreases in abundances were found for damselfly larvae (NOEC of 0.2 µg/L) and Sphaeriidae bivalves (NOEC of 20 µg/L), whereas Asellus aquaticus increased in abundance (NOEC <0.2 µg/L). Fluoxetine decreased photosynthetic activity and primary production of the suspended algae community. eDNA assessment provided additional insights by revealing that the algae belonging to the class Cryptophyceae and certain cyanobacteria taxa were the most negatively responding taxa to fluoxetine. Our results, together with results of others, suggest that fluoxetine can alter community structure and ecosystem functioning and that some impacts of fluoxetine on certain taxa can already be observed at environmentally realistic concentrations.


Subject(s)
Ecosystem , Water Pollutants, Chemical , Animals , Fluoxetine/toxicity , DNA Barcoding, Taxonomic , Fresh Water/chemistry , Zooplankton , Phytoplankton , Antidepressive Agents/pharmacology , Biological Assay , Water Pollutants, Chemical/analysis
11.
Fundam Clin Pharmacol ; 38(2): 320-327, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37937375

ABSTRACT

BACKGROUND: Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population. OBJECTIVES: Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems. METHODS: Male and female rats were gavaged with FLX (5 mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment. RESULTS: Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals. CONCLUSION: Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.


Subject(s)
Antidepressive Agents , Fluoxetine , Rats , Male , Female , Animals , Fluoxetine/toxicity , Antidepressive Agents/pharmacology , Liver
12.
Environ Toxicol Pharmacol ; 105: 104358, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38154759

ABSTRACT

Our study aimed to test whether fluoxetine impairs learning in fish and whether this potential impairment is reversible. Learning efficiency, with no aversive stimuli, of the Carassius carassius was analysed under different pharmaceutical conditions: (i) fish cultured without antidepressant (control), (ii) fish exposed to fluoxetine for 21 days (fluoxetine), and (iii) fish exposed to fluoxetine for 21 days and then cultured without fluoxetine for another 21 days (recovery). We exposed animals to environmental concentrations (360 ng L-1) of antidepressant. The learning rate was measured by timing how long it took the individual fish to find food and start feeding, six days in a row. The control and recovery fish took significantly less time to start eating over the six days. Control fish start eating 14 times faster than the fluoxetine fish. Fluoxetine can significantly affect learning and 21-day recovery period is not enough to fully restore the original learning abilities.


Subject(s)
Carps , Water Pollutants, Chemical , Animals , Fluoxetine/toxicity , Antidepressive Agents/toxicity
13.
Physiol Rep ; 11(23): e15881, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38031314

ABSTRACT

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin-dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short-term and long-term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.


Subject(s)
Depressive Disorder, Major , Prenatal Exposure Delayed Effects , Female , Mice , Animals , Humans , Fluoxetine/toxicity , Selective Serotonin Reuptake Inhibitors/toxicity , Depressive Disorder, Major/drug therapy , Serotonin , Bone and Bones , Prenatal Exposure Delayed Effects/drug therapy
14.
Sci Total Environ ; 905: 167391, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37758136

ABSTRACT

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is consistently introduced into the environment due to its ongoing consumption and inadequate removal by wastewater treatment plants. As a result, the scientific community has displayed a keen interest in investigating the potential toxicological effects associated with this medication. Nevertheless, there is a scarcity of available data regarding the impact of FLX on blood parameters. With this in mind, this study aimed to evaluate the potential toxicological consequences of FLX at environmentally significant concentrations (5, 16, and 40 ng/L) following a 96-hour acute exposure blood parameters in Danio rerio fish. Moreover, the investigation encompassed an assessment of oxidative stress parameters to determine whether the drug could induce disruptions in the REDOX status of the fish. The findings unveiled that FLX prompted the induction of oxidative stress in various organs of the fish, encompassing the liver, gut, brain, and gills. Notably, the gills and brain exhibited heightened susceptibility to the drug's effects compared to other organs. Furthermore, following acute exposure to FLX, there was an upregulation of antioxidant-related genes (sod, cat, gpx, nrf1, and nrf2), thereby providing additional evidence supporting the induction of oxidative stress in the organs of the fish. Lastly, FLX significantly impacted the customary values of various blood parameters, including glucose, blood urea nitrogen, alanine aminotransferase, alkaline phosphatase, red blood cell count, hemoglobin, and hematocrit. Thus, it can be inferred that FLX harmed the overall health status of the fish, resulting in the development of liver disease, anemia, and other associated illnesses.


Subject(s)
Fluoxetine , Zebrafish , Animals , Fluoxetine/toxicity , Zebrafish/physiology , Selective Serotonin Reuptake Inhibitors/toxicity , Oxidative Stress , Antioxidants/pharmacology
15.
Am J Physiol Gastrointest Liver Physiol ; 325(6): G528-G538, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37724979

ABSTRACT

Perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to disrupt the development of serotonergic signaling pathways in the brain and enteric nervous system. Serotonin (5-hydroxytryptamine; 5-HT) signaling is critical for gastrointestinal homeostasis; changes in 5-HT expression and regulation have been associated with gastrointestinal diseases of motility and inflammation. We tested the hypothesis that perinatal exposure to the SSRI fluoxetine can influence the development of the gastrointestinal tract in exposed offspring. Female nulliparous Wistar rats were given fluoxetine (10 mg/kg) or vehicle control from 2 wk before mating until weaning; small and large intestines of female and male offspring were collected at postnatal days 1, 21 (P1, P21, respectively), and 6 mo of age. In histological preparations, the proportion of serotonergic neurons significantly increased in the colons of both female and male fluoxetine-exposed compared with control offspring at P21, a time point that signifies maximal exposure to fluoxetine. At 6 mo of age, male but not female fluoxetine-exposed offspring had a significant increase in circulating 5-HT, with a significant decrease in transcripts encoding the 5-HT2A receptor and monoamine oxidase as compared with control offspring. Measurement of spatiotemporal mapping of contractile activity of the small and large intestine at 6 mo of age revealed no changes in motility in the small bowel of fluoxetine-exposed offspring but revealed a significant increase in the frequency of colonic contractions in the female fluoxetine-exposed compared with control animals. Susceptibility to inflammation was examined at 6 mo using the dextran sulfate sodium model of acute colitis. In utero exposure to fluoxetine was not found to exacerbate colitis severity. These findings suggest that fluoxetine exposure during fetal and early postnatal development can lead to changes in serotonergic neurons at the peak of exposure with sex-specific changes in 5-HT signaling and colonic motility in adulthood.NEW & NOTEWORTHY There is increasing recognition of the relevance of in utero and early postnatal exposures in the developmental programming of the gastrointestinal tract. Perinatal exposure to selective serotonin reuptake inhibitors and antidepressant medications is of particular relevance as they are commonly prescribed during pregnancy, and serotonergic pathways play key roles during gastrointestinal development and in postnatal homeostasis. Here, we provide a comprehensive evaluation of clinically relevant outcomes of gastrointestinal motility and susceptibility to colitis in fluoxetine-exposed offspring and highlight changes in colonic serotonergic neurons at the peak of perinatal fluoxetine exposure with sex-dependent changes in serotonin signaling and colonic motility in adulthood.


Subject(s)
Colitis , Prenatal Exposure Delayed Effects , Pregnancy , Humans , Rats , Animals , Male , Female , Fluoxetine/toxicity , Selective Serotonin Reuptake Inhibitors/toxicity , Serotonin/metabolism , Rats, Sprague-Dawley , Rats, Wistar , Prenatal Exposure Delayed Effects/metabolism , Inflammation , Colitis/chemically induced
16.
Toxicon ; 233: 107233, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37541601

ABSTRACT

This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals' behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects. In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined. Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg). Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 µg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated. Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared. According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.


Subject(s)
Fluoxetine , Rutaceae , Rats , Animals , Rats, Wistar , Fluoxetine/toxicity , Fluoxetine/therapeutic use , Seizures/chemically induced , Diazepam/toxicity , Diazepam/therapeutic use , Plant Extracts/toxicity
17.
J Toxicol Environ Health A ; 86(15): 534-542, 2023 08 03.
Article in English | MEDLINE | ID: mdl-37309916

ABSTRACT

The aim of the present study was to determine e whether a single acute 96 hr exposure of a glyphosate-based herbicide (GBH) to Nile tilapia fingerlings affected growth performance during the first 90 days of culture. This association was considered as GBH increases serotoninergic activity that affect fish anorexically. Although these findings were based upon chronic investigations, this study was designed to examine whether a single, acute, but excessive concentration GBH might impair growth performance in fish. In parallel, fish were also exposed to fluoxetine (FLU), a drug that selectively inhibits the reuptake of serotonin in brain synapses, leading to increased serotoninergic activity. Data demonstrated a decreased growth performance in fingerlings exposed to GBH or FLU compared to unexposed fingerlings. In fact, FLU-exposed fingerlings exhibited lower average weight and length, diminished weight gain, which resulted in lower final biomass. GBH-exposed fish, despite displaying a lower mean body weight, exhibited a biomass similar to biomass on controls. These body weight differences were noted after 30-60- and 90-day growth period in clean water. In an aquaculture context, these observed changes may be considered harmful to the production or economic performance of large-scale farming as currently practiced in tilapia farming.


Subject(s)
Cichlids , Herbicides , Animals , Herbicides/toxicity , Fluoxetine/toxicity , Body Weight , Glyphosate
18.
Sci Total Environ ; 876: 162746, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-36907389

ABSTRACT

Ecosystems around the world are increasingly polluted with pharmaceutical compounds that may perturb wildlife behaviour. Because many pharmaceuticals are continuously present in the aquatic environment, animals are often exposed to them across several life stages or even their entire life. Despite a large body of literature showing various impacts of exposure to pharmaceuticals on fish, hardly any long-term studies across different life stages have been conducted which makes it hard to accurately estimate the ecological outcomes of pharmaceutical pollution. Here, we performed a laboratory experiment in which we exposed hatchlings of the fish model Nothobranchius furzeri to an environmentally relevant concentration (0.5 µg/L) of the antidepressant fluoxetine until well into adulthood. We monitored total body length and geotaxic behaviour (i.e. gravity-mediated activity) of each fish as two traits that are ecologically relevant and naturally differ between juvenile and adult killifish. Fish exposed to fluoxetine were smaller compared to control fish, an effect that became more apparent as fish aged. Even though fluoxetine did not affect average swimming depth of either juveniles or adults, nor the time spent at the surface or bottom of the water column, exposed fish changed their position in the water column (depth) more frequently in the adult but not juvenile phase. These results suggest that important morphological and behavioural responses to pharmaceutical exposure-and their potential ecological consequences-may only emerge later in time and/or during specific life stages. Therefore, our results highlight the importance of considering ecologically relevant timescales across developmental stages when studying the ecotoxicology of pharmaceuticals.


Subject(s)
Environmental Pollutants , Fundulidae , Water Pollutants, Chemical , Animals , Fluoxetine/toxicity , Ecosystem , Water Pollutants, Chemical/toxicity , Pharmaceutical Preparations
19.
Chemosphere ; 326: 138446, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36940830

ABSTRACT

Pharmaceutical pollution is a major driver of global change, with the capacity to alter key behavioural and physiological traits in exposed animals. Antidepressants are among the most commonly detected pharmaceuticals in the environment. Despite well-documented pharmacological effects of antidepressants on sleep in humans and other vertebrates, very little is known about their ecologically relevant impacts as pollutants on non-target wildlife. Accordingly, we investigated the effects of acute 3-day exposure of eastern mosquitofish (Gambusia holbrooki) to field-realistic levels (nominal concentrations: 30 and 300 ng/L) of the widespread psychoactive pollutant, fluoxetine, on diurnal activity patterns and restfulness, as indicators of disruptions to sleep. We show that exposure to fluoxetine disrupted diel activity patterns, which was driven by augmentation of daytime inactivity. Specifically, unexposed control fish were markedly diurnal, swimming farther during the day and exhibiting longer periods and more bouts of inactivity at night. However, in fluoxetine-exposed fish, this natural diel rhythm was eroded, with no differences in activity or restfulness observed between the day and night. As a misalignment in the circadian rhythm has been shown to adversely affect fecundity and lifespan in animals, our findings reveal a potentially serious threat to the survival and reproductive success of pollutant-exposed wildlife.


Subject(s)
Cyprinodontiformes , Environmental Pollutants , Water Pollutants, Chemical , Animals , Humans , Fluoxetine/toxicity , Antidepressive Agents , Cyprinodontiformes/physiology , Circadian Rhythm , Animals, Wild , Water Pollutants, Chemical/toxicity
20.
Sci Total Environ ; 872: 162173, 2023 May 10.
Article in English | MEDLINE | ID: mdl-36775155

ABSTRACT

Fluoxetine is one of the worlds most prescribed antidepressant, and frequently detected in surface waters. Once present in the aquatic environment, fluoxetine has been shown to disrupt the swimming behaviour of fish and invertebrates. However, swimming behaviour is also known to be highly variable according to experimental conditions, potentially concealing relevant effects. Therefore, the aims of this study were two-fold: i) investigate the swimming and feeding behaviour of Gammarus pulex after exposure to the antidepressant fluoxetine (0.2, 2, 20, and 200 µg/L), and ii) assess to what degree the experimental test duration (short-term and long-term) and test location (laboratory and semi-field conditions) affect gammarid's swimming behaviour. We used automated video tracking and analysis to asses a range of swimming behaviours of G. pulex, including swimming speed, startle responses after light transition, acceleration, curvature and thigmotaxis. We found larger effects on the swimming behaviour of G. pulex due to experimental conditions than due to tested antidepressant concentrations. Gammarids swam faster, more straight and showed a stronger startle response during light transition when kept under semi-field conditions compared to the laboratory. Effects found for different test durations were opposite in the laboratory and semi-field. In the laboratory gammarids swam slower and spent more time at the inner zone of the arena after 2 days compared to 21 days while for the semi-field the reverse was observed. Fluoxetine had only minor impacts on the swimming behaviour of G. pulex, but experimental conditions influenced behavioural outcomes in response to fluoxetine exposure. Overall, our results highlight the importance of standardizing and optimizing experimental protocols that assess behaviour to achieve reproducible results in ecotoxicology.


Subject(s)
Amphipoda , Water Pollutants, Chemical , Animals , Fluoxetine/toxicity , Amphipoda/physiology , Swimming , Behavior, Animal , Antidepressive Agents/toxicity , Water Pollutants, Chemical/toxicity
SELECTION OF CITATIONS
SEARCH DETAIL
...