RESUMEN
Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.
Asunto(s)
Estroncio , Pez Cebra , Animales , Estroncio/química , Estroncio/farmacología , Especies Reactivas de Oxígeno/metabolismo , Embrión no Mamífero/efectos de los fármacos , Ensayo de Materiales , Hidroxiapatitas/química , Hidroxiapatitas/farmacología , Nanoestructuras/química , Larva/efectos de los fármacosRESUMEN
Facial masks are a source of plastic microfibres (PMFs) in the aquatic environment, an emerging risk factor for aquatic organisms. However, little is known concerning its impact during the early developmental stages of fish. Thus, the current study aimed to evaluate the potential interaction and developmental toxicity of PMFs derived from leachate of surgical masks (SC-Msk) and N-95 facial masks (N95-Msk) using a multi-biomarker approach in developing zebrafish (Danio rerio). PMFs from both facial masks were obtained and characterized by multiple techniques. Zebrafish embryos were exposed to environmentally relevant concentrations of PMFs from both facial masks (1000, 10,000, and 100,000 particle L-1), and the toxicity was analysed in terms of mortality, hatching rate, neurotoxicity, cardiotoxicity, morphological changes, reactive oxygen species (ROS) levels, cell viability, and behavioural impairments. The results showed that both facial masks can release PMFs, but the N95-Msk produced a higher concentration of PMFs than SC-Msk. Both PMFs can interact with zebrafish chorion and don't cause effects on embryo mortality and hatching; however, zebrafish embryos showed cardiotoxic effects, and larvae showed increased agitation, average speed, and distance travelled, indicating the behavioural impairments induced by PMFs derived from facial masks. Overall, results showed the risk of PMFs to the health of freshwater fish, indicating the need for greater attention to the disposal and ecotoxicological effects of facial masks on aquatic organisms.
Asunto(s)
Plásticos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Contaminantes Químicos del Agua/toxicidad , Plásticos/toxicidad , Máscaras , Embrión no Mamífero/efectos de los fármacosRESUMEN
Due to their broad-spectrum antimicrobial action and ease of synthesis, silver nanoparticles (AgNP) are one of the most widely used nanomaterials in different industrial and ecological areas. AgNP are released into marine ecosystems, nevertheless, their ecotoxicological effects have been overlooked. In this study, we evaluated the toxic effects of biogenic and synthesized AgNP (AgNPIBCLP11 and AgNPSINT) on sea urchin Echinometra lucunter embryos and compared them with the metal precursor silver nitrate (AgNO3). Fertilized eggs were exposed to five concentrations of the test compounds and a negative control for 48 h under controlled conditions. The IC50-48 h of AgNPIBCLP11, AgNPSINT and AgNO3 were 0.31, 4.095, and 0.01 µg L-1, evidencing that both AgNP are less toxic than AgNO3, and that AgNPSINT is less toxic than the AgNPIBCLP11. Toxicity to E. lucunter embryos could be explained by the fact that Ag affects DNA replication and induces the formation of pores in the cellular wall, leading to apoptosis.
Asunto(s)
Embrión no Mamífero , Nanopartículas del Metal , Erizos de Mar , Plata , Contaminantes Químicos del Agua , Animales , Plata/toxicidad , Nanopartículas del Metal/toxicidad , Erizos de Mar/efectos de los fármacos , Erizos de Mar/embriología , Embrión no Mamífero/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidadRESUMEN
The consumption of hormone-derived medicines, such as levonorgestrel (LNG), is increasing worldwide, and its discharge into the environment reaches non-target organisms. In our previous study, we exposed the parental generation of zebrafish to environmentally relevant concentrations of LNG during the developmental phase. Subsequently, they had grown in a tank with clean water until adulthood. Now, we allowed this parental generation to reproduce to obtain F1 progeny unexposed to LGN, in order to analyze the transgenerational effects of parental LNG exposure on the survival and hatching of unexposed F1 embryos and the stress and behavior of F1 larvae. Here, we found decreased survival rates with higher LNG concentrations, providing a transgenerational effect. This highlights the environmental impact of exposure to LNG, causing damage at the individual and population level and affecting the next generation at the beginning of development, impacting qualities in the survival of the species.
Asunto(s)
Levonorgestrel , Pez Cebra , Animales , Levonorgestrel/toxicidad , Femenino , Masculino , Embrión no Mamífero/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Larva/efectos de los fármacosRESUMEN
CONTEXT: The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes. OBJECTIVE: The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations. MATERIALS AND METHODS: Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h. RESULTS: HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD50 of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg. CONCLUSIONS: The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.
Asunto(s)
Bauhinia , Embrión no Mamífero , Extractos Vegetales , Hojas de la Planta , Pruebas de Toxicidad Aguda , Pez Cebra , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/aislamiento & purificación , Bauhinia/química , Embrión no Mamífero/efectos de los fármacos , Dosificación Letal Mediana , Relación Dosis-Respuesta a Droga , Tallos de la Planta , Etanol/toxicidad , Espectrometría de Masas en Tándem , Masculino , Solventes/química , FemeninoRESUMEN
The Villa Victoria dam is one of the most important storage reservoirs in Mexico since it distributes water to more than 20 million inhabitants in the Metropolitan Zone of Mexico City. In this dam, the common carp (Cyprinus carpio) is an important food resource for the inhabitants, so the aim of this work was to evaluate the oxidative damage (lipoperoxidation, oxidized proteins, antioxidant enzymes activity and gene expression), AChE, embryotoxicity and behavioral changes in C. carpio embryos and larvae exposed to water from Villa Victoria dam for 24, 48, 72 and 96 h. The embryotoxicity was evaluated trough the General Morphology Score (GMS) and the teratogenic index. Behavioral changes in basal locomotor activity and thigmotaxis were evaluated in a DanioVision, Noldus ™. An increase in lipid and protein oxidation as well as modification of CAT, SOD and GPx enzymatic activity was observed during the exposure times. The GMS indicated a low development in the embryos, the teratogenic index was less than 1, however teratogenic effects as yolk edema, fin malformation, head malformation and scoliosis were observed. In parallel, an increase in AChE activity and gene expression was observed reflecting changes in distance traveled of the basal locomotor activity and thigmotaxis at the sampling points. In conclusion, pollutants in water from Villa Victoria dam caused oxidative damage, changes in SOD, CAT, GPx and AChE activity as well as embryotoxicity and modifications in the behavior of C. carpio larvae. This study demonstrates the need to implement restoration programs for this reservoir since, contamination in the Villa Victoria dam could eventually endanger aquatic life and human health.
Asunto(s)
Acetilcolinesterasa , Carpas , Embrión no Mamífero , Larva , Estrés Oxidativo , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , México , Acetilcolinesterasa/metabolismo , Carpas/embriología , Carpas/metabolismo , Larva/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Conducta Animal/efectos de los fármacosRESUMEN
The increasing use of UV filters, such as benzophenone-3 (BP-3) and titanium dioxide nanoparticles (TiO2 NPs), has raised concerns regarding their ecotoxicological effects on the aquatic environment. The aim of the present study was to examine the embryo-larval toxicity attributed to BP-3 or TiO2 NPs, either alone or in a mixture, utilizing zebrafish (Danio rerio) as a model after exposure to environmentally relevant concentrations of these compounds. Zebrafish embryos were exposed to BP-3 (10, 100, or 1000 ng/L) or TiO2 NPs (1000 ng/L) alone or in a mixture (BP-3 10, 100, or 1000 ng/L plus 1000 ng/L of TiO2 NPs) under static conditions for 144 hr. After exposure, BP-3 levels were determined by high-performance liquid chromatography (HPLC). BP-3 levels increased in the presence of TiO2 NPs, indicating that the BP-3 degradation decreased in the presence of the NPs. In addition, in the presence of zebrafish, BP-3 levels in water decreased, indicating that zebrafish embryos and larvae might absorb BP-3. Data demonstrated that, in general, environmentally relevant concentrations of BP-3 and TiO2 NPs, either alone or in a mixture, did not significantly induce changes in heart and spontaneous contractions frequencies, levels of reactive oxygen species (ROS), morphological and morphometric parameters as well as mortality rates during 144 hr exposure. However, the groups exposed to TiO2 NPs alone and in a mixture with BP-3 at 10 ng/L exhibited an earlier significant hatching rate than the controls. Altogether, the data indicates that a potential ecotoxicological impact on the aquatic environment exists.
Asunto(s)
Benzofenonas , Embrión no Mamífero , Protectores Solares , Titanio , Contaminantes Químicos del Agua , Pez Cebra , Animales , Titanio/toxicidad , Titanio/química , Benzofenonas/toxicidad , Protectores Solares/toxicidad , Protectores Solares/química , Embrión no Mamífero/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Nanopartículas/toxicidad , Nanopartículas del Metal/toxicidad , Ecotoxicología , Larva/efectos de los fármacosRESUMEN
Pyriproxyfen (PPF), Bacillus thuringiensis israelensis (BTI), and malathion (MLT) are widely used worldwide to control the population of mosquitos that transmit arboviruses. The current work aimed to evaluate the toxicity of these single pesticides and their binary mixtures of PPF + BTI, PPF + MLT, and MLT + BTI on the embryo-larval stage of zebrafish (Danio rerio) as an animal model. Epiboly, mortality, apical endpoints, affected animals, heart rate, morphometric, thigmotaxis, touch sensitivity, and optomotor response tests were evaluated. PPF and MLT and all mixtures reduced the epiboly percentage. Mortality increased significantly in all exposed groups, except BTI, with MLT being the most toxic. The observed apical endpoints were pericardial and yolk sac edemas, and tail and spine deformation. Exposure to MLT showed a higher percentage of affected animals. A reduction in heart rate was also observed in MLT- and PPF + MLT-exposed groups. The PPF + MLT mixture decreased head measurements. Behavioral alterations were observed, with a decrease in thigmotaxis and touch sensitivity responses in PPF + MLT and MLT + BTI groups. Finally, optomotor responses were affected in all groups. The above data obtained suggest that the MLT + PFF mixture has the greatest toxicity effects. This mixture affected embryo-larval development and behavior and is close to the reality in several cities that use both pesticides for mosquito control rather than single pesticides, leading to a reevaluation of the strategy for mosquito control.
Asunto(s)
Bacillus thuringiensis , Larva , Malatión , Control de Mosquitos , Piridinas , Pez Cebra , Animales , Malatión/toxicidad , Control de Mosquitos/métodos , Piridinas/toxicidad , Larva/efectos de los fármacos , Insecticidas/toxicidad , Embrión no Mamífero/efectos de los fármacosRESUMEN
Ivermectin (IVM) is a broad-spectrum veterinary antiparasitic used worldwide in cattle breeding. The aim of this study was to evaluate the lethal effects of the active ingredient and a commercial formulation of IVM (1 % active ingredient) in the embryonic stage (S. 4-6) and larval stage (S. 25) of the South American amphibian Rhinella arenarum through chronic standardized bioassays. Also, behavior analysis and oxidative stress and cholinergic effects biomarkers were analyzed at 1, 10 and 100 µg IVM/L concentrations. For the embryonic stage, the active ingredient (96 h- LC50: 15900 µg/L) was more toxic than the commercial formulation (96 h-LC50: 51230 µg/L) during the acute period, while at chronic exposure the commercial formulation was more toxic (504 h-LC50: 10.25 µg/L), compared to the active ingredient (504 h-LC50: 312.80 µg/L). For the larval stage, in acute exposure, the active ingredient (96 h-LC50: 800 µg/L) was more toxic than the commercial formulation (96 h-LC50: 1550 µg/L). In the chronic exposure, the commercial formulation (504 h-LC50: 77.33 µg/L) was more toxic than the active ingredient (504 h-LC50: 195.25 µg/L). Overall, larvae exhibited greater sensitivity to both the active ingredient and the commercial formulation. However, during chronic exposure, embryos were more sensitive to the commercial formulation than larvae. The commercial formulation primarily induced oxidative stress, and both forms of the compound affected behavior and cholinergic effect biomarkers, even at low environmentally relevant concentrations (1 µg/L). These results highlight the potential impact of IVM on aquatic ecosystems.
Asunto(s)
Ivermectina , Larva , Estrés Oxidativo , Contaminantes Químicos del Agua , Animales , Ivermectina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Larva/efectos de los fármacos , Antiparasitarios/toxicidad , Bufonidae , Dosificación Letal Mediana , Ecotoxicología , Embrión no Mamífero/efectos de los fármacosRESUMEN
The Fundão dam collapse was one of the largest mining-related disasters globally. It resulted in the release of mining tailings containing heavy metals, which contaminated the Doce River in southeastern Brazil. This study assessed the effects of acute exposure of Danio rerio embryos to sediments contaminated by mine tailings six years after the Fundão dam collapse. The study sites included P2, P3, and P4 in the upper Doce River, as well as site P1 on the Piranga River, an uncontaminated river. Sediment samples were analyzed for 10 metals/metalloid by atomic absorption spectrometry. In the assays, embryos were exposed to sediment from P1-P4 sites, and uncontaminated quartz was used as control sediment. Various biomarkers were applied to assess biological responses, and the integrated biomarker response (IBR) index was calculated for each site. Sediment samples revealed elevated levels of As, Cr, Cu, Hg, and Ni beyond Brazilian legislation limits. At 96-h exposure, embryo mortality rates exceeded 20% in P1, P2, and P3, higher than the control and P4 (p < 0.0001). Hatching rates ranged from 60 to 80% in P1, P2, and P3, lower than the control and P4 (p < 0.001). Larvae exposed to P2 sediment (closest to the Fundão dam) exhibited skeletal, physiological, and sensory malformations. Neurotoxicity was indicated by increased acetylcholinesterase activity and reduced spontaneous movements in embryos exposed to Doce River sediment. Contamination also increased metallothionein and heat shock protein 70 levels, along with changes in cell proliferation and apoptosis. Principal component analysis showed a good correlation between metals/metalloid in the sediment and larval morphometric endpoints. The IBR index highlighted suitable biomarkers for monitoring metal contamination in fish embryos. Overall, our findings suggest that sediment toxicity following the Fundão dam failure may compromise the sustainability of fish communities in the Doce River.
Asunto(s)
Embrión no Mamífero , Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados , Ríos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Ríos/química , Sedimentos Geológicos/química , Embrión no Mamífero/efectos de los fármacos , Brasil , Monitoreo del Ambiente/métodos , Metales Pesados/toxicidad , Metales Pesados/análisis , Biomarcadores/metabolismo , MineríaRESUMEN
Ammonium and hexyltrimethylammonium thiomolybdates (ATM and ATM-C6) and thiotungstates (ATT and ATT-C6) were synthesized. Their toxicity was evaluated using both in vitro and in vivo approaches via the zebrafish embryo acute toxicity assay (ZFET), while the copper-thiometallate interaction was studied using cyclic voltammetry, as well as in an in vivo assay. Cyclic voltammetry suggests that all thiometallates form complexes with copper in a 2:1 Cu:thiometallate ratio. Both in vitro and in vivo assays demonstrated low toxicity in BALB/3T3 cells and in zebrafish embryos, with high IC50 and LC50 values. Furthermore, the hexyltrimethylammonium ion played a crucial role in enhancing viability and reducing toxicity during prolonged treatments for ATM and ATT. In particular, the ZEFT assay uncovered the accumulation of ATM in zebrafish yolk, averted by the incorporation of the hexyltrimethylammonium ion. Notably, the copper-thiometallate interaction assay highlighted the improved viability of embryos when cultured in CuCl2 and ATM-C6, even at high CuCl2 concentrations. The hatching assay further confirmed that copper-ATM-C6 interaction mitigates inhibitory effects induced by thiomolybdates and CuCl2 when administered individually. These results suggest that the incorporation of the hexyltrimethylammonium ion in ATM increase its ability to interact with copper and its potential application as a copper chelator.
Asunto(s)
Quelantes , Cobre , Molibdeno , Pez Cebra , Animales , Pez Cebra/embriología , Cobre/química , Quelantes/química , Quelantes/farmacología , Molibdeno/química , Molibdeno/farmacología , Ratones , Embrión no Mamífero/efectos de los fármacos , Células 3T3 BALB , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacologíaRESUMEN
Anticipating a global increase in cardiovascular diseases, there is an expected surge in the use of angiotensin-converting enzyme inhibitors, notably captopril (CAP). This heightened usage raises significant environmental apprehensions, mainly due to limited knowledge regarding CAP's toxic effects on aquatic species. In response to these concerns, the current study aimed to tackle this knowledge gap by evaluating the potential influence of nominal concentrations of CAP (0.2-2000 µg/L) on the embryonic development of Danio rerio. The findings revealed that CAP at all concentrations, even at concentrations considered environmentally significant (0.2 and 2 µg/L), induced various malformations in the embryos, ultimately leading to their mortality. Main malformations included pericardial edema, craniofacial malformation, scoliosis, tail deformation, and yolk sac deformation. In addition, CAP significantly altered the antioxidant activity of superoxide dismutase and catalase across all concentrations. Simultaneously, it elevated lipid peroxidation levels, hydroperoxides, and carbonylic proteins in the embryos, eliciting a substantial oxidative stress response. Likewise, CAP, at all concentrations, exerted significant modulatory effects on the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3), organogenesis (tbx2a, tbx2b, and irx3b), and ion exchange (slc12a1 and kcnj1) in Danio rerio embryos. Both augmentation and reduction in the expression levels of these genes characterized this modulation. The Pearson correlation analysis indicated a close association between oxidative damage biomarkers and the expression patterns of all examined genes with the elevated incidence of malformations and mortality in the embryos. In summary, it can be deduced that CAP poses a threat to aquatic species. Nevertheless, further research is imperative to enhance our understanding of the environmental implications of this pharmaceutical compound.
Asunto(s)
Captopril , Embrión no Mamífero , Desarrollo Embrionario , Contaminantes Químicos del Agua , Pez Cebra , Animales , Contaminantes Químicos del Agua/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Captopril/toxicidad , Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/toxicidadRESUMEN
Emodin is an anthraquinone secondary metabolite produced by several species of plants and fungi. Emodin is known for its pharmacological versatility, and, in the textile industry, for its good dyeing properties. However, its use in the textile industry can result in the formation and disposal of large volumes of wastewater. Emodin mutagenicity has been shown in bacteria and in human cells, but little is known about its possible toxic, genotoxic, or mutagenic effects in aquatic organisms. We have evaluated the eco/genotoxicity of emodin to aquatic organisms. Emodin was toxic to Daphnia similis (EC50 = 130 µg L-1) and zebrafish embryos (LC50 = 25 µg L-1). No toxicity was observed for Raphidocelis subcapitata, Ceriodaphnia dubia, or Parhyale hawaiensis. Additional biochemistry/molecular studies are needed to elucidate the toxic/mutagenic pathways of emodin in aquatic organisms. The PNEC value for emodin was 0.025 µg L-1. In addition to mutagenicity in the Salmonella/microsome assay, emodin was mutagenic in the micronucleus assay in the amphipod P. hawaiensis. Among the anthraquinone dyes tested to date, natural or synthetic, emodin was the most toxic to aquatic species.
Asunto(s)
Colorantes , Daphnia , Emodina , Pruebas de Mutagenicidad , Contaminantes Químicos del Agua , Pez Cebra , Emodina/toxicidad , Emodina/análogos & derivados , Animales , Colorantes/toxicidad , Daphnia/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Organismos Acuáticos/efectos de los fármacos , Mutágenos/toxicidad , Pruebas de Micronúcleos , Antraquinonas/toxicidad , Antraquinonas/química , Embrión no Mamífero/efectos de los fármacosRESUMEN
Monensin, an antibacterial commonly used in animal fattening, can enter aquatic ecosystems and harm non-target organisms. Since there are no previous studies about the effects of monensin on amphibians, the aim of the present study was to evaluate the lethal and sublethal toxicity of a commercial formulation of monensin (CFM) through standardized bioassays with embryos and larvae of the amphibian Rhinella arenarum. Oxidative stress (catalase and glutathione S-transferase activities, and reduced glutathione and lipid peroxidation levels), cholinesterasic effect (acetylcholinesterase and butyrylcholinesterase activities) and mutagenicity (micronuclei frequency) biomarkers were evaluated. The CFM produced teratogenic effects, with a teratogenic index of 6.21. Embryos (504â¯h-LC50: 273.33⯵g/L) were more sensitive than larvae, as no significant mortality was observed on larvae exposed up to 3000⯵g/L for 504â¯h. However, oxidative stress, cholinesterasic effect and mutagenicity biomarkers were altered on larvae exposed for 96â¯h to environmentally relevant concentrations (4, 12 and 20⯵g/L of monensin active ingredient). The CFM caused adverse effects on the exposed organisms, primarily on embryos, leading to lethal and sublethal effects, which could impact the wildlife when it reaches aquatic ecosystems.
Asunto(s)
Embrión no Mamífero , Larva , Monensina , Estrés Oxidativo , Contaminantes Químicos del Agua , Animales , Larva/efectos de los fármacos , Monensina/toxicidad , Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Acetilcolinesterasa/metabolismo , Teratógenos/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Bufo arenarum , Butirilcolinesterasa/metabolismo , Glutatión Transferasa/metabolismoRESUMEN
Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25-400 ngL-1) and high (500-1500 ngL-1) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL-1. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25-400 ngL-1), with a decrease in enzyme activity at high concentrations (500-1500 ngL-1). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL-1 of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
Asunto(s)
Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenitoína/toxicidad , Pez Cebra/embriología , Animales , Antioxidantes/metabolismo , Embrión no Mamífero/metabolismo , Desarrollo Embrionario/efectos de los fármacos , Enzimas/metabolismo , Pruebas de Toxicidad Aguda , Contaminantes Químicos del Agua/toxicidad , Proteínas de Pez Cebra/metabolismoRESUMEN
The antibiotic oxytetracycline (OTC) is commonly used in animal production and can enter aquatic ecosystems, causing adverse effects on non-target species. The aim of this work was to evaluate the lethal and sublethal effects of OTC on the embryonic and larval period of Rhinella arenarum, through standardized bioassays and oxidative stress (catalase-CAT-, superoxide dismutase-SOD-, glutathione S-transferase-GST-, reduced glutathione-GSH- and lipid peroxidation-TBARS-), neurotoxicity (acetylcholinesterase-AChE- and butyrylcholinesterase-BChE-) and genotoxicity (micronuclei test) biomarkers. Mortality was time and stage dependent, being the embryos (504 h-LC50 = 64.04 mg/L) more sensitive than the larvae (504 h-LC50 = 97.74 mg/L). Alterations in the oxidative stress biomarkers were observed mainly in larvae: CAT, SOD and GST decreased and GSH increased significantly. In embryos, only GST decreased significantly. Also, OTC increased the AChE and BChE activities but did not increase the micronuclei frequency. This study shows evidence that the presence of OTC in the environment may have negative effects on amphibians.
Asunto(s)
Antibacterianos/toxicidad , Bufo arenarum/crecimiento & desarrollo , Oxitetraciclina/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Biomarcadores , Butirilcolinesterasa/metabolismo , Embrión no Mamífero/efectos de los fármacos , Larva/efectos de los fármacos , Pruebas de Micronúcleos , Estrés Oxidativo , Contaminantes Químicos del Agua/toxicidadRESUMEN
17-Alpha-ethinylestradiol (EE2) is an estrogen derived from estradiol (E2). This compound and is one of the most widely used drugs both in humans and animals. Numerous studies have reported the ability of EE2 to alter sex determination and delay sexual maturity, but there are toxic effects that need to be explored. In this work, we analyzed the effect of EE2 on embryonic development and oxidative stress biomarkers in Danio rerio. For this effect, zebrafish embryos in the blastula period (2.5 h post fecundation) were exposed to different concentrations of EE2 (36-106 ng L-1) until 96 hpf. Survival, alterations to embryonic development, and teratogenic effects were evaluated using a stereomicroscope. Furthermore, oxidative stress biomarkers: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities, lipid peroxidation (LPX), hydroperoxide content (HPX), and protein carbonyl content (POX) were evaluated at 72 and 96 hpf using spectrophotometric methods. LC50 and EC50 of malformations got values of 82 ng L-1 and 57.7 ng L-1, respectively. The main teratogenic effects found were: chorda malformation, body malformation, and developmental delay. These alterations occurred at 86, 96, and 106 ng L-1. Integrated biomarker index showed that the oxidative stress biomarkers that had the most influence on embryos were SOD, CAT, GPX, and LPX. Overall, our results allow us to conclude that low concentrations of EE2 may potentially alter the development and oxidative status in the early life stages of zebrafish. Therefore, this bio-active estrogen can be considered a hazardous substance for fish.
Asunto(s)
Embrión no Mamífero/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Etinilestradiol/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/embriología , Animales , Biomarcadores/metabolismo , Monitoreo del Ambiente/métodos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Heat-labile toxin I (LT-I), produced by strains of enterotoxigenic Escherichia coli (ETEC), causes profuse watery diarrhea in humans. Different in vitro and in vivo models have already elucidated the mechanism of action of this toxin; however, their use does not always allow for more specific studies on how the LT-I toxin acts in systemic tracts and intestinal cell lines. In the present work, zebrafish (Danio rerio) and human intestinal cells (Caco-2) were used as models to study the toxin LT-I. Caco-2 cells were used, in the 62nd passage, at different cell concentrations. LT-I was conjugated to FITC to visualize its transport in cells, as well as microinjected into the caudal vein of zebrafish larvae, in order to investigate its effects on survival, systemic traffic, and morphological formation. The internalization of LT-I was visualized in 3 × 104 Caco-2 cells, being associated with the cell membrane and nucleus. The systemic traffic of LT-I in zebrafish larvae showed its presence in the cardiac cavity, yolk, and regions of the intestine, as demonstrated by cardiac edema (100%), the absence of a swimming bladder (100%), and yolk edema (80%), in addition to growth limitation in the larvae, compared to the control group. There was a reduction in heart rate during the assessment of larval survival kinetics, demonstrating the cardiotoxic effect of LT-I. Thus, in this study, we provide essential new depictions of the features of LT-I.
Asunto(s)
Toxinas Bacterianas/toxicidad , Escherichia coli Enterotoxigénica , Enterotoxinas/toxicidad , Proteínas de Escherichia coli/toxicidad , Animales , Toxinas Bacterianas/farmacocinética , Células CACO-2 , Edema/inducido químicamente , Embrión no Mamífero/anomalías , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Enterotoxinas/farmacocinética , Proteínas de Escherichia coli/farmacocinética , Cardiopatías Congénitas/inducido químicamente , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Intestinos/metabolismo , Miocardio/metabolismo , Saco Vitelino/efectos de los fármacos , Pez Cebra/anomalías , Pez Cebra/metabolismoRESUMEN
Glyphosate [N-(phosphonomethyl)glycine] is the active ingredient in widely used broad-spectrum herbicides. Even though the toxicity mechanism of this herbicide in vertebrates is poorly understood, evidence suggests that glyphosate is an endocrine disruptor capable of producing morphological anomalies as well as cardiotoxic and neurotoxic effects. We used the zebraï¬sh model to assess the effects of early life glyphosate exposure on the development of cartilage and bone tissues and organismal responses. We found functional alterations, including a reduction in the cardiac rate, significant changes in the spontaneous tail movement pattern, and defects in craniofacial development. These effects were concomitant with alterations in the level of the estrogen receptor alpha osteopontin and bone sialoprotein. We also found that embryos exposed to glyphosate presented spine deformities as adults. These developmental alterations are likely induced by changes in protein levels related to bone and cartilage formation.
Asunto(s)
Huesos/efectos de los fármacos , Anomalías Craneofaciales/inducido químicamente , Glicina/análogos & derivados , Herbicidas/toxicidad , Teratógenos/toxicidad , Animales , Huesos/anomalías , Anomalías Craneofaciales/metabolismo , Anomalías Craneofaciales/veterinaria , Embrión no Mamífero/anomalías , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Receptor alfa de Estrógeno/metabolismo , Femenino , Proteínas de Peces/metabolismo , Glicina/toxicidad , Frecuencia Cardíaca/efectos de los fármacos , Locomoción/efectos de los fármacos , Masculino , Osteopontina/metabolismo , Sialoglicoproteínas/metabolismo , Pez Cebra/anomalías , Pez Cebra/metabolismo , GlifosatoRESUMEN
2,4-Dichlorophenoxyacetic acid (2,4-D) herbicide is the main ingredient in over 1500 commercially available products such as Weedestroy® AM40 and DMA® 4 IVM. Although the liver has been identified as one of the organs that are affected by this herbicide, reports on its hepatotoxic effects available in the literature are restricted to rats. Thus, there is a gap in information on other organisms that may be vulnerable to 2,4-D exposure, such as fish. Therefore, the present work aimed to assess the hepatotoxic potential of 2,4-D in fish using zebrafish (Danio rerio) larvae as a model system. For this purpose, its acute toxicity to zebrafish embryos was assessed, as well as its sublethal effects (< LC50) on the activity of enzymes related to oxidative (GST, CAT and GPX) and metabolic (LDH) stress and liver parameters (AST, ALT and ALP) after 48 h of exposure. Morphological analyses of the liver were also assessed in zebrafish larvae. As a result, 2,4-D reduced larvae survival (LC50 15.010 mg/L in 96 h of exposure), induced malformations, altered the activity of LDH, GST and CAT enzymes and significantly increased the activity of all biomarkers for liver damage. Although no changes in the color or size of larval liver were observed, histopathological analysis revealed that treatment with 2,4-D caused severe changes in liver tissue, such as vacuolization of the cytosol, eccentric cell nucleus, loss of tissue architecture and cellular boundaries. Thus, the results showed that 2,4-D altered the enzymatic profile related to oxidative stress, and induces liver damage.