RESUMO
Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration. We have focused on developing novel DTIC salt/cocrystal forms with enhanced solubility and dissolution behaviors to overcome or minimize this undesirable biopharmaceutical profile. By cocrystallization techniques, two salts, two cocrystals, and one salt-cocrystal have been successfully prepared through reactions with aliphatic carboxylic acids. A detailed structural study of these new multicomponent crystals was conducted using X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Most DTIC crystal forms reported display substantial enhancements in solubility (up to 19-fold), with faster intrinsic dissolution rates (from 1.3 to 22-fold), contributing positively to reducing the photodegradation of DTIC in solution. These findings reinforce the potential of these new solid forms to enhance the limited DTIC biopharmaceutical profile.
Assuntos
Cristalização , Dacarbazina , Fotólise , Solubilidade , Difração de Raios X , Dacarbazina/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Ressonância Magnética , Varredura Diferencial de CalorimetriaRESUMO
Tropical rivers are the main destinations for tailings from urban, industrial and agricultural activities in the region studied. The present study aimed to investigate if early stages of zebrafish (Danio rerio) development is a viable biological model to assess the toxicity of surface waters of tropical rivers, and whether that toxicity could be correlated to standard water quality indexes. Embryos were exposed to samples from 55 sites from 10 hydrographic basins of rivers in Pernambuco State, northeastern Brazil. Lethality rates, sublethal toxicity based on the general morphology score (GMS) and frequencies of abnormalities were analyzed. Significant mortality was observed in samples of 7 basins. The GMS indicated significant delay in embryo-larval development in 50% of the samples. The highest toxicity was detected in basins within Recife metropolitan area, where 61% of the samples caused sublethal toxicity. Most frequent developmental abnormalities included non-inflation of the swim bladder, delayed hatching and blood stasis. The highest frequencies of blood stasis were detected in samples with highest NH3 concentrations, corroborated by a positive correlation suggesting the existence of a causal relationship. A significant correlation was detected between water quality indexes and GMS with a greater toxic effect being observed in samples collected in areas of greater urban density and greater contamination by domestic sewage. This study demonstrates that the early stages of the zebrafish is a viable ecotoxicological model to assess the toxicity of surface waters and can contribute to a better understanding between the chemical composition and the adverse effects suffered by fish early life stage fish in tropical rivers.
Assuntos
Rios , Peixe-Zebra , Animais , Brasil , Qualidade da Água , Modelos BiológicosRESUMO
Un-ionized ammonia (NH3) is a prevalent contaminant found in aquatic ecosystems, frequently associated with complex mixtures of other toxic contaminants. Early embryo-larval stages of zebrafish Danio rerio became an important model for water quality monitoring, and it is necessary to characterize its susceptibility to NH3 exposure. Fertilized eggs were exposed to NH3 concentrations ranging from 0.02 to 5.23 mg NH3 L-1 until 168 h postfertilization (hpf). The lethal concentration to 50% of exposed zebrafish during 96 h was 2.07 mg NH3 L-1, 25% above the median value reported values for early developmental stages of fishes. Sublethal toxicity endpoints indicated the lowest observed effect concentrations for slow blood circulation at 24 hpf, decreased heart ventricular contractions at 72 hpf, incomplete yolk sac absorption at 96 hpf, failure in swim bladder inflation at 96 hpf, developmental retardation at 96 hpf, decreased total length, decreased swimming speed, altered trajectories, and acetylcholinesterase inhibition at 168 hpf of 0.85, 0.06, 0.15, 0.06, 0.15, 0.61, 1.35, 0.35, and 0.85 mg NH3 L-1, respectively. Environmentally relevant NH3 concentrations can affect zebrafish's early development and larval viability, and our results help discriminate NH3 contribution to the toxicity of complex environmental mixtures when zebrafish is used in water quality monitoring.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Amônia/toxicidade , Acetilcolinesterase/farmacologia , Ecossistema , Embrião não Mamífero , Poluentes Químicos da Água/toxicidade , LarvaRESUMO
The Capibaribe River provides water to a population of 1.7 million people in the Brazilian northeast, while receiving agricultural runoff and industrial and domestic effluents along its 280 km. The present study evaluated the ecotoxicity of surface waters along ten sites in rural and urban areas using zebrafish (Danio rerio) early-life stages and related it to water quality indices and chemical abiotic variables. Lethality rates, delays in embryo-larval development quantified by the general morphology score (GMS), and frequencies of developmental abnormalities were analyzed. A correlation was detected between zebrafish GMS and water quality index (WQI), sensitivity to domestic sewage contamination, and trophic state index, focused on eutrophication. These indices agreed in identifying a spatial pattern of smaller impact in terms of ecotoxicity, domestic sewage contamination, and eutrophication risk at three sites in rural areas (mean GMS 16.9), an intermediate impact at four sites with urban and agricultural influence (mean GMS 16.4), and greatest impacts at three more urbanized sites (mean GMS 14.9). Most frequent developmental abnormalities included noninflation of the swim bladder, delayed hatching, nonprotrusion of the mouth, blood stasis, and nondevelopment of pectoral fins. Toxic NH3 concentrations varied spatially, with higher concentrations in urban sites; and blood stasis correlated positively with NH3 , suggesting a causal relationship. Polycyclic aromatic hydrocarbons were detected in both rural and urbanized sites, contributing to detected toxicity. The present study demonstrates the potential of zebrafish early-life stages as an ecotoxicological model that may contribute to a better understanding of surface water quality and ecotoxicity in tropical river systems. Environ Toxicol Chem 2021;40:3063-3077. © 2021 SETAC.
Assuntos
Rios , Poluentes Químicos da Água , Animais , Brasil , Monitoramento Ambiental , Humanos , Esgotos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-ZebraRESUMO
Contamination of aquatic habitats by endocrine disruptor chemicals is a major concern globally. This study evaluated histochemical, behavioral, and reproductive effects on adult male Poecilia vivipara sampled from Capibaribe River Estuarine System (CRES), compared to laboratory control males after breeding with virgin control females. CRES is contaminated by a mixture of estrogenic contaminants estrone, 17ß-estradiol, estriol, 17α-Ethinylestradiol, bisphenol A and caffeine in concentrations averaging 13.9; 4.2; 19.5; 8.6; 27 and 23.2 ng L-1, respectively. Estrogenic risk in 17ß-estradiol-equivalent-concentrations is above probable no effect concentrations. Males sampled from CRES indicated liver phosphoprotein induction, decreased number of contacts and copulation attempts when paired with control females, slower swimming speed and lower female impregnation success rates, compared to control males. A reduction of 62% in fecundity was observed in control females paired with field sampled males compared with control males. Our results highlight hazards posed to fish reproduction by estrogenic micropollutants.
Assuntos
Poecilia , Poluentes Químicos da Água , Animais , Estrona/análise , Estuários , Feminino , Masculino , Reprodução , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Polycyclic aromatic hydrocarbons (PAH) in bile and biochemical biomarkers were evaluated in Brazilian mojarra Eugerres brasilianus along four estuaries in northeastern Brazil. Bile PAHs naphthalene, phenanthrene chrysene, pyrene and benzo[a]pyrene were lowest at Formoso River Estuarine System (FRES), an area with low population density focused on tourism. Fish sampled in Suape Estuarine Complex (SEC), where a growing industrial port complex is established indicated higher naphthalene and pyrene concentrations compared with FRES. Fish sampled in highly urbanized and populated Bacia do Pina Estuarine Complex (BPEC) and Barra de Jangada Estuarine System (BJES) indicated an increase in all PAHs compared to FRES. Activities of phase 1 Ethoxyresorufin-O-deethylase, phase 2 glutathione-S-transferase and antioxidant defense catalase were induced up to 20, 2 and 2-fold in BJES and BPEC compared to FRES. This study confirms E. brasilianus as an important sentinel species, providing baseline information for these tropical estuaries with different degrees of anthropogenic pressure.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Biomarcadores , Brasil , Monitoramento Ambiental , Estuários , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análiseRESUMO
The tropical estuarine guppy Poecilia vivipara was used to address fish early life stage toxicity caused by the antifouling contaminant tributyltin. Six-day-old P. vivipara were exposed for 7 d to control water and waterborne tributyltin at 15.8, 83.8, 716, and 818 ng tin (Sn) L-1 . After exposure, swimming, feeding, growth, and eye histological endpoints were evaluated. Histopathological analysis of the retinal pigment epithelium (RPE) indicated alterations in pigment positioning at all tributyltin concentrations. A dose-dependent increase in photoreceptor layer disorganization and iris melanin hyperpigmentation was verified, and high frequencies of RPE invaginations and iris epithelial cell atrophy were observed even at the lowest exposure concentration of 15.8 ng Sn L-1 . At the highest exposure level (818 ng Sn L-1 ) fish also presented reductions in swimming speed, swimming resistance, daily capture of Artemia nauplii, and growth in weight of 85, 60, 33, and 56% relative to controls, respectively. This association between retinal histopathology and reduced swimming and foraging behavior can reduce recruitment to the adult population. Environ Toxicol Chem 2020;39:1953-1963. © 2020 SETAC.
Assuntos
Comportamento Animal/efeitos dos fármacos , Desinfetantes/toxicidade , Olho/efeitos dos fármacos , Poecilia/crescimento & desenvolvimento , Reprodução/efeitos dos fármacos , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Olho/patologia , Retina/efeitos dos fármacos , Retina/parasitologia , NataçãoRESUMO
PURPOSE: The objective of this study was to evaluate the immediate bone damage and bone repair after osteotomy for implants using conventional drills and drills powered by piezoelectric motor. MATERIALS AND METHODS: Twelve rabbits received a tibial osteotomy with a conventional drill (control), with a diamond like carbon drill (DLC) and with a piezoelectric drill (Piezo). The animals were euthanized immediately, 30 and 60 days postoperatively. The tibias were removed and analyzed by means of histomorphometry, immunohistochemistry and microtomography. RESULTS: The immediate damage to the tissue at the cavity margins was similar (P > .05). At 30 and 60 days, the amount of newly formed bone tissue was similar (P > .05). Osteocalcin was intense score at 60 days in Piezo group. Microtomography revealed that bone volume at 30 days (control 3.8; DLC 4.3; and Piezo 2.4) and 60 days (control 4.9; DLC 4.82; and Piezo 3.95) were similar. There was a significant difference in bone formation between 30 (2.4) and 60 days (3.95) for the Piezo group (P = .016). CONCLUSION: The immediate effects and repair of cavities made using conventional, DLC coated, or ultrasound drills were similar.
Assuntos
Implantes Dentários , Piezocirurgia , Animais , Sobrevivência Celular , Osteotomia , Estudos Prospectivos , CoelhosRESUMO
In this work we determine the linear and non-linear optical properties of a Fluoro-N-Acylhydrazide derivative (FBHZ), using a combined supermolecule approach and an iterative scheme of electrostatic polarization, where the atoms of neighbouring molecules are represented by point charges. Our results for non-linear optics (NLO) are comparable to those found experimentally, suggesting that FBHZ constitutes an attractive object for future studies and for use as an interesting material for third-order NLO applications. The dynamic electrical properties of FBHZ in different solvent media are reported. Its molecular properties are closely related to supramolecular features; accordingly, we analysed all its crystal structure properties via intermolecular interactions in the solid state, using X-ray crystallography data and Hirshfeld surface (HS), including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and hot-stage microscopy (HSM), where the results reveal crystal stability in respect to temperature variation.
Assuntos
Compostos de Benzilideno/química , Varredura Diferencial de Calorimetria , Cristalografia por Raios X , Modelos Teóricos , Estrutura Molecular , TermogravimetriaRESUMO
Used petroleum hydrocarbons and gasoline stations runoff are significant sources of polycyclic aromatic hydrocarbons (PAHs) to aquatic ecosystems. Samples of the final effluent of oil-water-separators were collected at gasoline stations in the metropolitan region of Recife, Brazil, before release to sewage or rainwater systems. Effluent soluble fractions (ESF) were prepared and bioassays were performed according to the Fish Embryo Toxicity Test. The test involved exposing zebrafish Danio rerio embryos to dilutions of the ESFs for 96 h, with daily examination of lethality and sublethal morphological effects integrated through the General Morphology Score (GMS), based on the achievement of developmental hallmarks. Frequencies of abnormalities were recorded after exposures. ESF LC50-96h (lethal concentration to 50% of exposed embryos) in the most toxic effluent achieved 8.9% (v/v), equivalent to 11 µg phenanthrene equivalents L-1. GMS scores indicated significantly delayed embryo-larval development at ESF dilutions of 10% and 20% from effluents of all gas stations. Major abnormalities detected after the 96 h exposure included the presence of a yolk sac not fully absorbed coupled with the lack of an inflated swim bladder, lack of both pectoral fins, and the failure to develop a protruding mouth. Effective equivalent PAH concentrations that induce a 50% frequency of larvae without an inflated swim bladder (EC50) were 4.9 µg phenanthrene L-1, 21.8 µg naphthalene L-1, and 34.1 µg chrysene L-1. This study shows that PAHs in ESFs from gas stations oil water separators are toxic to zebrafish, contributing to the toxicity of urban storm waters.