Prolonged exposure to the synthetic glucocorticoid dexamethasone induces brain damage via oxidative stress and apoptotic response in adult Daniorerio.

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.

Spirulina (Arthrospira maxima) mitigates the toxicity induced by a mixture of metal and NSAID in Xenopus laevis.

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.

Women with preeclampsia exposed to air pollution during pregnancy: Relationship between oxidative stress and neonatal disease - Pilot study.

Oxidative imbalance as a pathophysiological mechanism has been reported as an adverse outcome in pregnant women who develop preeclampsia and in their newborns. Furthermore, emerging evidence suggests the same mechanism by which air pollutants may exert their toxic effects. Therefore, the objective of the study was to evaluate the biomarkers of oxidative stress and their relationship with neonatal disease in premature newborns from mothers with preeclampsia exposed to air pollution during pregnancy. The data of air pollutants (PM2.5, PM10 and ozone) were collected at fixed monitoring stations. Oxidative and antioxidant status markers were obtained through special techniques in women with preeclampsia and in umbilical cord blood of their premature newborns. The oxidative stress markers were significantly higher in women with preeclampsia and their newborns who were exposed to higher levels of ambient air pollutants in the first and second trimester of pregnancy. Neonatal diseases are associated with preeclampsia in pregnancies, specifically intrauterine growth restriction (IUGR) and necrotizing enterocolitis (NEC). A significant correlation was identified in the levels of prooxidant agents and antioxidant enzyme activity in the presence of neonatal diseases associated with preeclampsia. There is increased oxidative damage in both the maternal and fetal circulation in women who develop preeclampsia exposed to air pollution during pregnancy. Therefore, these pregnancies complicated by preeclampsia have a greater adverse outcome as neonatal disease in the preterm infant.

Developmental alterations, teratogenic effects, and oxidative disruption induced by ibuprofen, aluminum, and their binary mixture on Danio rerio.

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.

Protective effects of Spirulina (Arthrospira maxima) against toxicity induced by cadmium in Xenopus laevis.

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.

Long-term exposure to environmentally relevant concentrations of ibuprofen and aluminum alters oxidative stress status on Danio rerio.

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.

Evaluation of Teratogenicity of Pharmaceuticals Using FETAX.

Pharmaceuticals are chemical compounds which are used to preserve human and animal health. Once administered, these compounds are metabolized or can remain unaltered until excreted. Therefore, a mixture of pharmaceuticals and their metabolites enters municipal sewers and wastewater treatment plants where, depending on their polarity, water solubility, and persistence, they cannot be completely removed or transformed during the treatment process, so that unaltered pharmaceuticals and/or their metabolites can enter surface water. As a result, in recent years concern has grown about trace concentrations and the risk they pose to ecosystems, considering the annual increase in pharmaceutical production and use at world level.This chapter reviews the frog embryo teratogenesis assay-Xenopus (FETAX). Originally developed during the mid-1980s as a test for detecting the developmental toxicity of pure chemical products and complex mixtures in the laboratory, in recent years it has been used to evaluate the mechanisms of action, biotransformation, and detoxification of xenobiotics as well as in ecotoxicology studies using alternative species and in situ monitoring.

Determination of metals and pharmaceutical compounds released in hospital wastewater from Toluca, Mexico, and evaluation of their toxic impact.

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 96 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.