RESUMO
Due to its extensive use as a painkiller, anti-inflammatory, and immune modulatory agent, as well as its effectiveness in treating severe COVID-19, dexamethasone, a synthetic glucocorticoid, has gained attention not only for its impact on public health but also for its environmental implications. Various studies have reported its presence in aquatic environments, including urban waters, surface samples, sediments, drinking water, and wastewater effluents. However, limited information is available regarding its toxic effects on nontarget aquatic organisms. Therefore, this study aimed to investigate the mechanism of toxicity underlying dexamethasone-induced brain damage in the bioindicator Danio rerio following long-term exposure. Adult zebrafish were treated with environmentally relevant concentrations of dexamethasone (20, 40, and 60 ng L-1) for 28 days. To elucidate the possible mechanisms involved in the toxicity of the pharmaceutical compound, we conducted a behavioral test battery (Novel Tank and Light and Dark tests), oxidative stress biomarkers, acetylcholinesterase enzyme activity quantification, histopathological analysis, and gene expression analysis using qRT-PCR (p53, bcl-2, bax, caspase-3, nrf1, and nrf2).The results revealed that the pharmaceutical compound could produce anxiety-like symptoms, increase the oxidative-induced stress response, decrease the activity of acetylcholinesterase enzyme, and cause histopathological alterations, including perineuronal vacuolization, granular and molecular layers deterioration, cell swallowing and intracellular spaces. The expression of genes involved in the apoptotic process (p53, bax, and casp-3) and antioxidant defense (nrf1 and nrf2) was upregulated in response to oxidative damage, while the expression of the anti-apoptotic gene bcl-2 was down-regulated indicating that the environmental presence of dexamethasone may pose a threat to wildlife and human health.
Assuntos
Apoptose , Dexametasona , Estresse Oxidativo , Poluentes Químicos da Água , Peixe-Zebra , Animais , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Dexametasona/toxicidade , Poluentes Químicos da Água/toxicidade , Glucocorticoides/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/induzido quimicamenteRESUMO
Cadmium (Cd) is often detected in the environment due to its wide use in industry; also, NSAIDs are one of the most consumed pharmaceuticals, particularly diclofenac (DCF). Several studies have reported the presence of both contaminants in water bodies at concentrations ranging from ng L-1 to µg L-1; in addition, they have shown that they can induce oxidative stress in aquatic species and disturb signal transduction, cell proliferation, and intercellular communication, which could lead to teratogenesis. Spirulina has been consumed as a dietary supplement; its antioxidant, anti-inflammatory, neuroprotective, and nutritional properties are well documented. This work aimed to evaluate if Spirulina reduces the damage induced by Cd and DCF mixture in Xenopus laevis at early life stages. FETAX assay was carried out: 20 fertilized oocytes were exposed to seven different treatments on triplicate, control, Cd (24.5 µg L-1), DCF (149 µg L-1), Cd + DCF, Cd+DCF+Spirulina (2 mg L-1), Cd+DCF+Spirulina (4 mg L-1), Cd+DCF+Spirulina (10 mg L-1), malformations, mortality, and growth were evaluated after 96 h, also lipid peroxidation, superoxide dismutase and catalase activity were determined after 192 h. Cd increased DCF mortality, Cd and DCF mixture increased the incidence of malformations as well as oxidative damage; on the other hand, the results obtained show that Spirulina can be used to reduce the damage caused by the mixture of Cd and DCF since it promotes growth, reduce mortality, malformations, and oxidative stress in X. laevis.
Assuntos
Anti-Inflamatórios não Esteroides , Spirulina , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Spirulina/metabolismo , Xenopus laevis , Cádmio/toxicidade , Diclofenaco/toxicidade , Estresse Oxidativo , Antioxidantes/farmacologia , MetaisRESUMO
Several studies highlighted the ubiquitous presence of ibuprofen and aluminum in the aquatic environment around the world and demonstrated their potential to induce embryotoxic and teratogenic defects on aquatic species individually. Although studies that evaluate developmental alterations induced by mixtures of these pollutants are scarce; and, since environmental contamination presented in the form of a mixture of toxicants with different chemical properties and toxicity mechanisms capable of generating interactions; the objective of this study was to evaluate the developmental defects, teratogenic alterations, and oxidative stress induced by individual forms and the mixture of ibuprofen (IBU) and aluminum (Al) on zebrafish embryos. Oocytes exposed to environmentally relevant concentrations of IBU (0.1-20 µg L-1) and Al (0.01-8 mg L-1) and one binary mixture. The LC50 and EC50 were obtained to calculate the teratogenic index (TI). The IBU LC50, EC50, and TI were 8.06 µg L-1, 2.85 µg L-1 and 2.82. In contrast, Al LC50 was 5.0 mg L-1with an EC50 of 3.58 mg L-1 and TI of 1.39. The main alterations observed for individual compounds were hatching alterations, head malformation, skeletal deformities, hypopigmentation, pericardial edema, and heart rate impairment. The mixture also showed significant delays to embryonic development. Moreover, oxidative stress biomarkers of cellular oxidation and antioxidant defenses at 72 and 96 hpf significantly increased. Results show that environmentally relevant concentrations of ibuprofen (IBU), aluminum (Al), and their mixture promote a series of developmental defects, teratogenic effects, and oxidative disruption on D. rerio embryos, and the interaction of both substances altered the response. In conclusion, morphological and biochemical tests are suitable tools for assessing the health risk of aquatic wildlife by exposure to individual and mixed pollutants in freshwater bodies.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Alumínio/metabolismo , Animais , Embrião não Mamífero/metabolismo , Ibuprofeno/metabolismo , Ibuprofeno/toxicidade , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Spirulina (Arthrospira maxima) has been recognized as a superfood and nutraceutical by its high nutritional value and the benefits of its consumption; it is an important source of lipids, proteins, vitamins, minerals, and antioxidants. It is known that spirulina has positive effects on the toxicity induced by pharmaceuticals and metals. Heavy metals such as cadmium, frequently used in industrial activities, are continuously detected in water bodies and can generate adverse effects on aquatic organisms even at low concentrations. This study aimed to evaluate the protective effect of spirulina (Arthrospira maxima) against the toxic effects induced by cadmium in the early life stages of Xenopus laevis. Twenty Xenopus laevis embryos were exposed to five different treatments on triplicate, control, cadmium (CdCl2 24.5 µg L-1) and three spirulina mixtures Cd + S 1 (24.5 µg L-1 CdCl2 + 2 mg L-1 spirulina), Cd + S 2 (24.5 µg L-1 CdCl2 + 2 mg L-1 spirulina), Cd + S 3 (24.5 µg L-1 CdCl2 + 10 mg L-1 spirulina); after 96 h of exposure: Malformations, mortality and length were evaluated; also, after 192 h, lipid peroxidation (LPX), superoxide dismutase (SOD) and catalase (CAT) were determined. All spirulina treatments decreased mortality from 34 to 50% and reduced malformations on incidence from 36 to 68%. Treatment Cd + S 3 decreased growth inhibition significantly. Spirulina treatment Cd + S 2 decreased lipidic peroxidation and antioxidant activity; these results suggest that spirulina (Arthrospira maxima) can decrease the mortality, frequency of malformations, the severity of malformations, growth inhibition, and oxidative damage induced by cadmium in Xenopus laevis embryos.
Assuntos
Cloreto de Cádmio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Spirulina , Poluentes Químicos da Água/toxicidade , Xenopus laevis , Anormalidades Induzidas por Medicamentos/prevenção & controle , Animais , Catalase/genética , Catalase/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Larva/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Despite the ubiquitous presence of multiple pollutants in aqueous environments have been extensively demonstrated, the ecological impact of chemical cocktails has not been studied in depth. In recent years, environmental studies have mainly focused on the risk assessment of individual chemical substances neglecting the effects of complex mixtures even though it has been demonstrated that combined effects exerted by pollutants might represent a greater hazard to the biocenosis. The current study evaluates the effects on the oxidative stress status induced by individual forms and binary mixtures of ibuprofen (IBU) and aluminum (Al) on brain, gills, liver and gut tissues of Danio rerio after long-term exposure to environmentally relevant concentrations (0.1-11 µg L-1 and 0.05 mg L-1- 6 mg L-1, respectively). Lipid peroxidation (LPO), Protein carbonyl content (PCC) and activity of Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPX) were evaluated. Moreover, concentrations of both toxicants and the metabolite 2-OH-IBU were quantified on test water and tissues. Results show that ibuprofen (IBU) and aluminum (Al) singly promote the production of radical species and alters the oxidative stress status in all evaluated tissues of zebrafish, nevertheless, higher effects were elicited by mixtures as different interactions take place.
Assuntos
Alumínio/toxicidade , Antioxidantes/metabolismo , Ibuprofeno/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Alumínio/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/toxicidade , Encéfalo/efeitos dos fármacos , Química Encefálica , Relação Dose-Resposta a Droga , Esquema de Medicação , Trato Gastrointestinal/química , Brânquias/química , Ibuprofeno/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/química , Carbonilação Proteica , Testes de Toxicidade , Poluentes Químicos da Água/química , Peixe-ZebraRESUMO
Due to the activities inherent to medical care units, the hospital effluent released contains diverse contaminants such as tensoactives, disinfectants, metals, pharmaceutical products and chemical reagents, which are potentially toxic to the environment since they receive no treatment or are not effectively removed by such treatment before entering the drain. They are incorporated into municipal wastewater, eventually entering water bodies where they can have harmful effects on organisms and can result in ecological damage. To determine the toxicological risk induced by this type of eflluents, eight metals and 11 pharmaceuticals were quantified, in effluent from a hospital. Developmental effects, teratogenesis and oxidative stress induction were evaluated in two bioindicator species: Xenopus laevis and Lithobates catesbeianus. FETAX (frog embryo teratogenesis assay-Xenopus) was used to obtain the median lethal concentration (LC50), effective concentration inducing 50% malformation (EC50), teratogenic index (TI), minimum concentration to inhibit growth (MCIG), and the types of malformation induced. Twenty oocytes in midblastula transition were exposed to six concentrations of effluent (0.1, 0.3, 0.5, 0.7, 0.9, 1%) and negative and positive (6-aminonicotinamide) controls. After 96â¯h of exposure, diverse biomarkers of oxidative damage were evaluated: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the antioxidant enzymes superoxide dismutase and catalase. TI was 3.8 in X. laevis and 4.0 in L. catesbeianus, both exceed the value in the FETAX protocol (1.2), indicating that this effluent is teratogenic to both species. Growth inhibition was induced as well as diverse malformation including microcephaly, cardiac and facial edema, eye malformations, and notochord, tail, fin and gut damage. Significant differences relative to the control group were observed in both species with all biomarkers. This hospital effluent contains contaminants which represents a toxic risk, since these substances are teratogenic to the bioindicators used. The mechanism of damage induction may be associated with oxidative stress.
Assuntos
Metais/análise , Preparações Farmacêuticas/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Anormalidades Induzidas por Medicamentos , Animais , Bioensaio , Embrião não Mamífero/efeitos dos fármacos , Monitoramento Ambiental , Metais/toxicidade , México , Carbonilação Proteica , Rana catesbeiana , Teratogênicos/toxicidade , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade , Xenopus laevisRESUMO
Steviol glycosides are sweetening compounds from the Stevia rebaudiana Bertoni plant. This product is considered safe for human consumption and was approved as a food additive by the Food and Drugs Administration (FDA) and European Food Safety Authority (EFSA). Its effects on the ecosystem have not been studied in depth; therefore, it is necessary to carry out ecotoxicological studies in organisms such as Cyprinus carpio. The present study aimed to evaluate the antioxidant activity by SGs on diverse tissues in C. carpio using oxidative stress (OS) biomarkers. To test the antioxidant activity, carps were exposed to four systems: (1) SGs free control, (2) CCl4 0.5 mL/kg, (3) SGs 1 g/L, and (4) CCl4 0.5 mL/kg + SGs 1 g/L at 96 h. The following biomarkers were analyzed: lipoperoxidation (LPX), hydroperoxide content (HPC), and protein carbonyl content (PCC), as well as antioxidant activity of superoxide dismutase (SOD) and catalase (CAT). It was found that both (3 and 4) systems' exposure decreases LPX, CHP, PCC, SOD, and CAT with respect to the CCl4 system. The results of this study demonstrate that the concentrations of SGs used are not capable of generating oxidative stress and, on the contrary, would appear to induce an antioxidant effect.