RESUMEN
Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006-500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.
Asunto(s)
Inhibidores de Captación Adrenérgica/toxicidad , Antidepresivos Tricíclicos/toxicidad , Nortriptilina/toxicidad , Inhibidores Selectivos de la Recaptación de Serotonina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra , Acetilcolinesterasa/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Larva/efectos de los fármacos , Locomoción/efectos de los fármacosRESUMEN
At ecosystems level, environmental parameters such as temperature, pH, dissolved oxygen concentration and intensity of UV radiation (UVR) have an important role on the efficiency of organisms' physiological and behavioral performances and consequently on the capacity of response to contaminants. Insignificant alterations of these parameters may compromise this response. In addition, these parameters can additionally alter chemical compounds by inducing their degradation, producing thereafter other metabolites. Understanding the combined effects of chemicals and environmental parameters is absolutely necessary for an adequate prediction of risk in aquatic environments. According to this scenario, this work aims at studying the combined toxicity of UVR and three xenobiotics: the biocide triclosan (TCS), the metal chromium (as potassium dichromate, PD) and the fungicide prochloraz (PCZ). To achieve this goal zebrafish (Danio rerio) embryos (3h post fertilization (hpf)) were exposed to several concentrations of each chemical combined with different UV intensities; mortality and eggs were recorded every 24h for the all test duration (96 h). Results showed different response patterns depending on the toxicant, stress levels and duration of exposure. The combination of UVR and TCS indicated a dose ratio deviation where synergism was observed when UVR was the dominant stressor (day 2). The combination of UVR and PD presented a dose level dependency at day 3 indicating antagonism at low stress levels, changing with time where at day 4, a dose ratio deviation showed statistically that synergism occurred at higher PD concentrations. Finally, UVR combined with PCZ indicated a dose ratio at day 3 and dose level deviation at day 4 of exposure, suggesting a synergistic response when PCZ is the dominant stressor in the combination. The obtained results in this study highlighted the importance of taking into account the possible interaction of stressors and time of exposure to better predict environmental risk.
Asunto(s)
Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/efectos de la radiación , Imidazoles/toxicidad , Dicromato de Potasio/toxicidad , Triclosán/toxicidad , Rayos Ultravioleta , Animales , Antiinfecciosos Locales/toxicidad , Fungicidas Industriales/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez CebraRESUMEN
Psychiatric pharmaceuticals are one of the most prescribed active substances globally. Bupropion (BPP) is an antidepressant that acts via inhibition of norepinephrine and dopamine reuptake. It has been found in various water matrices, and thus its effects on aquatic organisms must be studied. The present study aimed to evaluate the acute toxic effects of BPP on zebrafish (Danio rerio) early life stages. For developmental analysis, organisms were exposed for 168â¯h to concentrations ranging from 0 to 82000⯵g/L. Two other experiments were performed by exposing embryos to a wide range of concentrations (from 0 to 50000⯵g/L) in order to evaluate BPP effects on embryonic behavior, using the Zebrabox and testing at the biochemical level (acetylcholinesterase, glutathione-S-transferase, lactate dehydrogenase and catalase). Developmental analysis indicated that BPP had low acute toxicity with a calculated 168 h-LC50 of 50346⯵g/L. Concentrations equal to or above 44800⯵g/L elicited several effects such as hatching delay, edemas and tail deformities. However, concentrations from 7300⯵g/L upwards elicited equilibrium alteration. Behavioral analysis showed that BPP affected zebrafish locomotor behavior by decreasing activity at 0.6⯵g/L, increasing activity at 8.8 and 158⯵g/L, and decreasing activity at 50000⯵g/L. Biochemical analysis showed an increase of AChE activity at 158 and 2812⯵g/L, an increase in GST at the highest concentrations, CAT alteration and increase of LDH at 0.6, 2812 and 50000⯵g/L. We can conclude that BPP affects zebrafish early life stages at environmental concentrations.
Asunto(s)
Bupropión/farmacología , Embrión no Mamífero/efectos de los fármacos , Pez Cebra/fisiología , Acetilcolinesterasa/efectos de los fármacos , Animales , Organismos Acuáticos/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Bupropión/toxicidad , Catalasa/efectos de los fármacos , Embrión no Mamífero/enzimología , Glutatión Transferasa/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidadRESUMEN
Climate change is expected to alter the dynamics of water masses, with consequent changes in water quality parameters such as dissolved organic carbon (DOC) concentration. DOC levels play a critical role in the fate of organic chemicals, influencing their bioavailability and toxicity to aquatic organisms. This study aimed to evaluate the effects of DOC, particularly humic acids (HA), in the toxicity of gemfibrozil (GEM) - a human pharmaceutical frequently detected in surface waters. Lethal and sublethal effects (genotoxic, biochemical and behavioural alterations) were evaluated in zebrafish embryos exposed to several concentrations of GEM and three HA levels, in a full factorial design. HA significantly increased GEM LC50 values, mainly in the first 72â¯h of exposure, showing a protective effect. At sublethal levels, however, such protection was not observed since HA per se elicited adverse effects. At a biochemical level, individual exposure to HA (20â¯mg/L) elicited significant decreases in cholinesterase and glutathione S-transferase activities. Regarding behaviour, effects of individual exposure to HA appear to surpass the GEM effects, reducing the total distance moved by larvae. Both GEM and HA significantly increased DNA damage. Hence, this study demonstrated that abiotic factors, namely HA, should be considered in the assessment of pharmaceuticals toxicity. Moreover, it showed that lethality may not be enough to characterize combined effects since different patterns of response may occur at different levels of biological organization. Testing sublethal relevant endpoints is thus recommended to achieve a robust risk assessment in realistic scenarios.
Asunto(s)
Embrión no Mamífero/efectos de los fármacos , Gemfibrozilo/toxicidad , Sustancias Húmicas/efectos adversos , Animales , Colinesterasas/metabolismo , Interacciones Farmacológicas , Glutatión Transferasa/metabolismo , Humanos , Larva/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/embriología , Pez Cebra/fisiologíaRESUMEN
Ayahuasca is a psychoactive concoction prepared from the plants Banisteriopsis caapi and Psychotria viridis which are used ancestrally by Amazonian Indian populations and more recently, by Christian religious groups in Brazil and other countries. The aims of the present study were to identify the effects of ayahuasca on zebrafish embryo development and neurobehavior. Toxicity and developmental endpoints for zebrafish embryos were assessed from 0 to 1000â¯mg/L over 96â¯h of exposure. The effects on locomotor activity of zebrafish larvae were assessed using a video tracking system (ZebraBox) from 0 to 20â¯mg/L and after 120 and 144â¯h of exposure. The LC50 of ayahuasca in zebrafish was determined as 236.3â¯mg/L. Ayahuasca exposure caused significant developmental anomalies in zebrafish embryos, mainly at the highest concentration tested, including hatching delay, loss of equilibrium, edema and the accumulation of red blood cells. Embryo behavior was also significantly affected, with decreased locomotor activity at the highest concentration tested. These results are in accordance with data obtained in mammal studies highlighting the possible risks of uncontrolled use of ayahuasca. Further research employing more specific behavior analysis could provide additional data on both therapeutic benefits and possible toxicological risk of ayahuasca.
Asunto(s)
Banisteriopsis/química , Locomoción/efectos de los fármacos , Extractos Vegetales/farmacología , Pez Cebra/crecimiento & desarrollo , Animales , Banisteriopsis/metabolismo , Conducta Animal/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Larva/efectos de los fármacos , Estadios del Ciclo de Vida/efectos de los fármacos , Extractos Vegetales/químicaRESUMEN
During the last century the increase in the mean global temperatures has been shown to impact on freshwater physicochemical parameters such as pH, dissolved oxygen, or ultraviolet (UV) light abundance. Changes in these parameters could modify the toxicity of environmental pollutants. Therefore, in the present study, the authors studied the tolerance (survival and sublethal endpoints) of zebrafish (Danio rerio) embryos to variations in pH (3-12), dissolved oxygen (3.9-237 µmol/L) and UV intensity (55-467 mW/m2 ) using selected endpoints. Sublethal endpoint assessment included the quantification of hatching success, developmental delay, reduction of body length, frequency of edema, and morphological abnormalities. Median lethal concentrations (LC50s; 96-h) of 3.68 and 10.21 were determined for acid and alkaline pH, respectively. Embryo survival appeared to be relatively resistant to oxygen depletion with a 96-h LC50 of 0.42 mg/L. However, concentrations of 6 mg/L and below caused edema and developmental retardations. Continuous exposure to UV radiation affected zebrafish development by reducing survival and hatching rate and triggering a series of developmental abnormalities such as pericardial edema and deformities. A 72-h LC50 of 227 mW/m2 was derived from intensity-response modeling. By generation of concentration-response parameters the authors' data provide a basis for the subsequent assessment of combined effect of environmental stress parameters and chemicals. Environ Toxicol Chem 2017;36:682-690. © 2016 SETAC.
Asunto(s)
Embrión no Mamífero , Oxígeno/análisis , Rayos Ultravioleta , Contaminantes Químicos del Agua/toxicidad , Pez Cebra , Animales , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/efectos de la radiación , Concentración de Iones de Hidrógeno , Dosificación Letal Mediana , Oxígeno/farmacología , Pez Cebra/crecimiento & desarrolloRESUMEN
Carbendazim is a widely used broad spectrum benzimidazole fungicide; however, its effects to non-target aquatic organisms are poorly studied. The aim of this study was to investigate the toxic effects of carbendazim to zebrafish early life stages at several levels of biological organization, including developmental, biochemical and behavioural levels. The embryo assay was done following the OECD guideline 236 and using a concentration range between 1.1 and 1.8mg/L. Lethal and developmental endpoints such as hatching, edemas, malformations, heart beat rate, body growth and delays were assessed in a 96h exposure. A sub-teratogenic range (from 0.16 to 500µg/L) was then used to assess effects at biochemical and behavioural levels. Biochemical markers included cholinesterase (ChE), glutathione-S-transferase (GST), lactate dehydrogenase (LDH) and catalase (CAT) and were assessed at 96h. The locomotor behaviour was assessed using an automated video tracking system at 120h. Carbendazim (96h-LC50 of 1.75mg/L) elicited several developmental anomalies in zebrafish embryos with EC50 values ranging from 0.85 to 1.6mg/L. ChE, GST and LDH activities were increased at concentrations equal or above 4µg/L. The locomotor assay showed to be extremely sensitive, detecting effects in time that larvae spent swimming at concentrations of 0.16µg/L and thus, being several orders of magnitude more sensitive that developmental parameters or lethality. These are ecological relevant concentrations and highlight the potential of behavioural endpoints as early warning signs for environmental stress. Further studies should focus on understanding how the behavioural disturbances measured in these types of studies translate into fitness impairment at the adult stage.
Asunto(s)
Conducta Animal/efectos de los fármacos , Bencimidazoles/toxicidad , Carbamatos/toxicidad , Fungicidas Industriales/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/fisiología , Animales , Bencimidazoles/análisis , Carbamatos/análisis , Catalasa/metabolismo , Colinesterasas/metabolismo , Cromatografía Líquida de Alta Presión , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/fisiología , Fungicidas Industriales/análisis , Glutatión Transferasa/metabolismo , Larva/efectos de los fármacos , Larva/fisiología , Locomoción/efectos de los fármacos , Natación , Espectrometría de Masas en Tándem , Contaminantes Químicos del Agua/análisis , Pez Cebra/crecimiento & desarrolloRESUMEN
This study aimed to assess the effect of ultraviolet radiation (UVR) and chemical stress (triclosan-TCS; potassium dichromate-PD; prochloraz-PCZ) on bacterial communities of zebrafish (Danio rerio) embryos (ZEBC). Embryos were exposed to two UVR intensities and two chemical concentrations not causing mortality or any developmental effect (equivalent to the No-Observed-Effect Concentration-NOEC; NOEC diluted by 10-NOEC/10). Effects on ZEBC were evaluated using denaturing gradient gel electrophoresis (DGGE) and interpreted considering structure, richness and diversity. ZEBC were affected by both stressors even at concentrations/doses not affecting the host-organism (survival/development). Yet, some stress-tolerant bacterial groups were revealed. The structure of the ZEBC was always affected, mainly due to xenobiotic presence. Richness and diversity decreased after exposure to NOEC of PD. Interactive effects occurred for TCS and UVR. Aquatic microbiota imbalance might have repercussions for the host/aquatic system, particularly in a realistic scenario/climate change perspective therefore, future ecotoxicological models should consider xenobiotics interactions with UVR.