RESUMO
Plastic contamination in aquatic ecosystems all around the world is on the rise. Microplastics (MPs) interfere with the ecological functions of different aquatic animals, including zooplankton. Other contaminants can also be transported by microplastics, resulting in higher toxicity. Here, we evaluated the effect of microplastics alone and in combination with cyanotoxins (CT) on the demographic and feeding responses of the freshwater rotifer Brachionus calyciflorus. The microplastics used were polystyrene spheres of 30 µm diameter. The cyanobacteria were obtained from a sample collected from the Valle de Bravo reservoir in Central Mexico, and the secondary metabolites were obtained after 5 cycles of freezing, thawing and sonication. We conducted acute (LC50, 24h bioassay) and chronic toxicity tests involving population growth, life table experiments, and feeding experiments. The LC50 value using microplastics was 21.91 mg/L, and for the cyanobacterial crude extract it was 2.56 µg/L, but the combination of both resulted in a higher adverse effect (16.64 mg/L) due to the microplastics. Rotifer survival, reproduction, and feeding decreased in the presence of either MPs or CT but the adverse effect was more in the presence of both contaminants. We found that the adverse effects of MPs and CT on the test rotifer species were enhanced when exposed to both contaminants simultaneously.
Assuntos
Cianobactérias , Microplásticos , Rotíferos , Poluentes Químicos da Água , Animais , Rotíferos/efeitos dos fármacos , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Microcistinas/toxicidade , Reprodução/efeitos dos fármacos , MéxicoRESUMO
The present study aims to evaluate the toxicity of the green calcium oxide nanoparticles (CaO-NPs) from golden linseed extract (Linum usitatissimum L.) by phytotoxicity in seeds (Daucus carota, Beet shankar, Lactuca sativa and Brassica oleracea), in vitro safety profile and soil toxicity for CaO-NPs solutions from 12.5 to 100 µg mL-1. Ecotoxicity analysis of the soil was conducted using XRD diffractograms, which revealed characteristic peaks of the nanoparticles at 37.35° (12.5, 25, 50, and 100 µg mL-1), as well as a peak at 67.34° (25 and 100 µg mL-1). Additionally, the in vitro safety assessment indicated favorable cell specification and regulation within the first 24 h, demonstrating reductions of 15.9 ± 0.2%, 17.9 ± 0.2%, 17.6 ± 0.2%, and 32.9 ± 0.2% to 12.5, 25, 50, and 100 µg mL-1, respectively. The dsDNA assay revealed initial protection and controlled release within the cells for 48 h. However, after 72 h, there was an increase of 20 ± 0.2%, 16 ± 0.2%, 32 ± 0.2%, and 43 ± 0.2% to 12.5, 25, and 50 µg mL-1. The analysis of ROS generation demonstrated a reduction of 40 ± 0.2%, 33 ± 0.2%, 20 ± 0.2%, and 9 ± 0.2% to 12.5, 25, 50, and 100 µg mL-1, respectively, within 72 h. When compared to the negative control (NC), there was an increase of 50 ± 0.2%, 56 ± 0.2%, 77 ± 0.2%, and 92 ± 0.2% at the same concentrations, suggesting that the nanoparticles generated free radicals, leading to cellular inflammation. This was attributed to the positive surface charge of the nanoparticles, resulting in reduced interaction with the cell membrane and the subsequent release of hydroxyl (â¢OH), which caused inflammatory processes in the cells. Therefore, CaO-NPs exhibited a low phytotoxicity and high cytocompatibility, while also promoting plant germination and growth.
Assuntos
Compostos de Cálcio , Nanopartículas , Óxidos , Compostos de Cálcio/toxicidade , Compostos de Cálcio/química , Óxidos/toxicidade , Óxidos/química , Nanopartículas/toxicidade , Nanopartículas/química , Humanos , Poluentes do Solo/toxicidade , Brassica/efeitos dos fármacos , Brassica/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Solo/químicaRESUMO
In recent decades the Amazonian ecosystem has received large amounts of domestic and industrial effluents, as well as mining-related waste contributing significant quantities of metal to water bodies. Thus, the main objective of the study was to verify the sensitivity of a native Amazonian ostracod (Strandesia rondoniensis) species to isolated and mixed metal salts (CuSO4; ZnCl2; CdCl2 and HgCl2). The sensitivity will be compared to other species using species sensitivity distributions (SSDs) for an ecological risk assessment (ERA). The experiment consisted of simultaneously exposing each metal alone and in mixture, through a factorial design for toxicity with 25 different combinations for 48 h. For the ERA, metal concentrations measured in the water of various aquatic environments in the Amazon basin were considered based on the risk quotient values. The results showed that the metal toxicity gradient was Cd>Hg>Cu>Zn, respectively. The toxicity in the mixture showed that the combination of Cu-Cd and Cu-Zn better fit the model (CA), indicating mainly synergism when copper predominated in the mixture. Meanwhile, the Cu-Hg interaction fit the model better (IA), again indicating synergism when copper was at a higher concentration. The ERA showed a high risk (RQ > 1) for the Cd, Cu, and Hg metals.
Assuntos
Crustáceos , Monitoramento Ambiental , Poluentes Químicos da Água , Medição de Risco , Poluentes Químicos da Água/toxicidade , Animais , Crustáceos/efeitos dos fármacos , Brasil , Metais Pesados/toxicidade , Metais/toxicidade , Testes de ToxicidadeRESUMO
Mimosa tenuiflora (Fabaceae) is popularly known in Brazil as "Jurema preta". From the bark of its root, "jurema wine" is obtained, a psychedelic drink used in Indigenous religious rituals in Northeastern Brazil. This work aimed to investigate the chemical composition and acute oral toxicity of the ethanolic extract of the root bark from M. tenuiflora (EEMt). EEMt was analyzed by UPLC-QToF-MS/MS and DI-ESI-IT-MSn. Oral administration of EEMt was performed once at doses of 300 and 2000 mg/kg in female Swiss mice. Signs and symptoms of intoxication, as well as mortality were monitored for 14 days. Thirteen compounds were annotated in EEMt: eight type B proanthocyanidins, three alkaloids, a glycosylated flavonol, and a dihydrochalcone derivative. The acute administration of 300 and 2000 mg/kg of EEMt did not show mortality. It also did not change the food intake or body weight of the animals. However, the relative weights of the kidneys were significantly changed for both doses. Changes in hematological and biochemical parameters were found. In addition, histopathological changes were also observed in the heart, liver, and kidneys. Thus, based on our findings, EEMt presented an LD50 greater than 2000 mg/kg and was therefore classified in category 5 of the Globally Harmonized Classification System (GHS). EEMt showed acute oral toxicity by altering hematological, biochemical and histological parameters.
Assuntos
Mimosa , Casca de Planta , Extratos Vegetais , Raízes de Plantas , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Camundongos , Feminino , Casca de Planta/química , Raízes de Plantas/química , Mimosa/química , Brasil , Testes de Toxicidade Aguda , Espectrometria de Massas em Tandem , Metabolômica , Etanol/químicaRESUMO
(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.
Assuntos
Monoterpenos Cicloexânicos , Monoterpenos , Ocitocina , Útero , Animais , Ocitocina/farmacologia , Feminino , Monoterpenos Cicloexânicos/farmacologia , Camundongos , Útero/efeitos dos fármacos , Monoterpenos/farmacologia , Contração Uterina/efeitos dos fármacos , Ratos , Ratos Wistar , Parassimpatolíticos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Carbacol/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. is a medicinal species belonging to the Anacardiaceae family. It is commonly referred to as "aroeira" and its leaves and roots are utilized for treating different pathological conditions. However, despite its widespread use in traditional medicine, there is a lack of in-depth toxicological studies. AIM: To evaluate the acute toxicity and genotoxicity of S. molle aqueous extract/ethanol-soluble fraction in rats. MATERIAL AND METHODS: First, a purified aqueous extract was obtained from the leaves of S. mole through infusion (referred to as EESM) and its compounds were identified using LC-DAD-MS data. Female rats were then subjected to acute oral toxicity tests using doses of 5, 50, 300, and 2000 mg/kg of ESSM. Studies on genetic material, including the micronucleus test and comet assay, were conducted on male and female Wistar rats using the same doses as in the acute toxicity test. For both assays, ESSM was administered orally. RESULTS: The main metabolites annotated from ESSM were dimeric proanthocyanidins, phenylpropanoids acids, flavan-3-ols, simple organic acids (C6-C1), a flavonol di-O-glycosylated (rutin), and O-glycosylated megastigmane. The ESSM did not exhibit any acute toxic effects, such as changes in biochemical, hematologic, or histopathological analysis. Furthermore, no changes were observed in comet assay or micronucleus tests when rats were given doses of 5, 50, 300, or 2000 mg/kg of ESSM. CONCLUSION: The results showed that the ESSM does not induce acute toxicity or exhibit genotoxicity up to a dose of 2000 mg/kg.
Assuntos
Testes para Micronúcleos , Extratos Vegetais , Folhas de Planta , Ratos Wistar , Testes de Toxicidade Aguda , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Feminino , Masculino , Folhas de Planta/química , Ratos , Anacardiaceae/química , Etanol/química , Etanol/toxicidade , Dano ao DNA/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Mutagênicos/toxicidade , SchinusRESUMO
Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD50) values by using Lorke's method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the ß-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B-O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that the LD50 value for both compounds was 1265 mg/kg, while the effective dose 50 (ED50) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications.
RESUMO
Punica granatum, popularly known as pomegranate, is a fruit tree with wide worldwide distribution, containing numerous phytochemicals of great medicinal value. The aim of the present study was to determine the phytochemical profile and antioxidant potential of a protein fraction (PF) derived from P. granatum sarcotesta which is rich in lectin. In addition, the acute oral toxicity, genotoxicity and antigenotoxicity of this protein fraction (PF) from P. granatum sarcotesta was measured. The phytochemical profile of PF was determined using HPLC. The in vitro antioxidant effect was assessed using the methods of total antioxidant capacity (TAC) and DPPH and ABTS+ radical scavenging. Acute oral toxicity was determined in female Swiss mice administered a single dose of 2000 mg/kg. This PF was examined for genotoxicity and antigenotoxicity at doses of 500, 1000 and 2000 mg/kg, utilizing mouse peripheral blood cells. Phytochemical characterization detected a high content of ellagic acid and antioxidant capacity similar to that of ascorbic acid (positive control). PF was not toxic (LD50 >2000 mg/kg) and did not exert a genotoxic effect in mice. PF protected the DNA of peripheral blood cells against damage induced by cyclophosphamide. In conclusion, this PF fraction exhibited significant antioxidant activity without initiating toxic or genotoxic responses in mice.
Assuntos
Antioxidantes , Extratos Vegetais , Punica granatum , Animais , Camundongos , Antioxidantes/farmacologia , Feminino , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Punica granatum/química , Lectinas/toxicidade , Testes de Mutagenicidade , Dano ao DNA/efeitos dos fármacos , Testes de Toxicidade AgudaRESUMO
The use of the brine shrimp Artemia salina (Leach) in acute toxicity assays has great potential due to its simplicity, low cost and reproducibility. In the current study, some of the variables that can influence the reliability of the assay in terms of test organism survival, were evaluated as part of its implementation in our laboratory. The quality and type of water used, the buffer components and other parameters (salinity, pH and dissolved oxygen level), were all evaluated for optimisation purposes. DMSO (dimethyl sulphoxide) was used as the test substance in the toxicity assay, to evaluate the concentration limits as a solvent in sample preparation. Regarding the buffer salinity, pH and dissolved oxygen level, we found that a 25% to 30% deviation from the standard values did not affect the survival of the nauplii (the first-instar larval stage) under assay conditions. In summary, we corroborate the potential use of this model for the prediction of the toxic potential of substances, to inform future testing strategies.
Assuntos
Artemia , Testes de Toxicidade Aguda , Animais , Artemia/efeitos dos fármacos , Testes de Toxicidade Aguda/métodos , Concentração de Íons de Hidrogênio , Salinidade , Dimetil Sulfóxido/toxicidadeRESUMO
Microbial pigments are considered as one of the main sources of natural types, and the attention to them is increasing in the food and pharmaceutical industries. This study aimed to investigate the effects of pigments extracted from Micrococcus roseus (PEM) on the gene expression of a and b staphylococcal enterotoxins (sea and seb) and their acute toxicity. Real-time PCR was used to study the anti-enterotoxigenic activity of PEM against Staphylococcus aureus at sub-inhibitory concentrations. In addition, the acute toxicity of PEM was evaluated on albino mice through alkaline phosphatase (ALP), aspartate aminotransferas (AST), and alanine aminotransferase (ALT) of liver and its histopathological changes. Based on the results, the expression of sea and seb was decreased in the presence of PEM at sub-inhibitory concentrations. The 2-∆∆CT was measured 0.02 and 0.01 for the expression of sea and seb of S. aureus grown in the MHB containing 16 mg/ml PEM. The results showed that the expression of seb is more sensitive to PEM compared to the expression of sea. After treatment of mice with PEM for two weeks, the condition of mice was normal, and the results of liver enzymatic activities and histopathological changes showed insignificant difference compared to the control sample.
Assuntos
Enterotoxinas , Fígado , Pigmentos Biológicos , Staphylococcus aureus , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Fígado/patologia , Fígado/efeitos dos fármacos , Enterotoxinas/genética , Enterotoxinas/toxicidade , Enterotoxinas/metabolismo , Micrococcus/efeitos dos fármacos , Micrococcus/genética , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Infecções Estafilocócicas/microbiologia , Masculino , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Testes de Sensibilidade Microbiana , Alanina Transaminase/metabolismo , Alanina Transaminase/sangueRESUMO
Water and several chemicals, including dyestuffs, surfactants, acids, and salts, are required during textile dyeing processes. Surfactants are harmful to the aquatic environment and induce several negative biological effects in exposed biota. In this context, the present study aimed to assess acute effects of five surfactants, comprising anionic and nonionic classes, and other auxiliary products used in fiber dyeing processes to aquatic organisms Vibrio fischeri (bacteria) and Daphnia similis (cladocerans). The toxicities of binary surfactant mixtures containing the anionic surfactant dodecylbenzene sulfonate + nonionic fatty alcohol ethoxylate and dodecylbenzene sulfonate + nonionic alkylene oxide were also evaluated. Nonionic surfactants were more toxic than anionic compounds for both organisms. Acute nonionic toxicity ranged from 1.3 mg/L (fatty alcohol ethoxylate surfactant) to 2.6 mg/L (ethoxylate surfactant) for V. fischeri and from 1.9 mg/L (alkylene oxide surfactant) to 12.5 mg/L (alkyl aryl ethoxylated and aromatic sulfonate surfactant) for D. similis, while the anionic dodecylbenzene sulfonate EC50s were determined as 66.2 mg/L and 19.7 mg/L, respectively. Both mixtures were very toxic for the exposed organisms: the EC50 average in the anionic + fatty alcohol ethoxylate mixture was of 1.0 mg/L ± 0.11 for V. fischeri and 4.09 mg/L ± 0.69 for D. similis. While the anionic + alkylene oxide mixture, EC50 of 3.34 mg/L for D. similis and 3.60 mg/L for V. fischeri. These toxicity data suggested that the concentration addition was the best model to explain the action that is more likely to occur for mixture for the dodecylbenzene sulfonate and alkylene oxide mixtures in both organisms. Our findings also suggest that textile wastewater surfactants may interact and produce different responses in aquatic organisms, such as synergism and antagonism. Ecotoxicological assays provide relevant information concerning hazardous pollutants, which may then be adequately treated and suitably managed to reduce toxic loads, associated to suitable management plans.
Assuntos
Aliivibrio fischeri , Benzenossulfonatos , Daphnia , Tensoativos , Águas Residuárias , Poluentes Químicos da Água , Tensoativos/toxicidade , Poluentes Químicos da Água/toxicidade , Águas Residuárias/química , Aliivibrio fischeri/efeitos dos fármacos , Animais , Daphnia/efeitos dos fármacos , Ecotoxicologia , TêxteisRESUMO
The xanthone lichenxanthone did not show toxic effects (LC50>1.0â mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5â mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.
Assuntos
Ibuprofeno , Peixe-Zebra , Animais , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Canais IônicosRESUMO
Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175-5,000 mg·kg-1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg-1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.
Assuntos
Celulose , Excipientes , Nicotiana , Ratos Wistar , Animais , Feminino , Celulose/toxicidade , Celulose/administração & dosagem , Celulose/química , Excipientes/toxicidade , Excipientes/química , Administração Oral , Testes de Toxicidade Subcrônica , Ratos , Testes de Toxicidade Aguda , Nanofibras/toxicidade , Química Verde , Relação Dose-Resposta a DrogaRESUMO
Malpighia emarginata has a high amount of vitamin C with pharmacological or food preservation potential. However, despite its wide use and application possibilities its toxicity in repeated doses and for a long time (6 months) has not yet been studied. In this context, this study aimed to evaluate the acute toxicity and repeated doses from fruits of this plant. The extract was produced with the pulp (EMe) of the lyophilized fruit and submitted to chromatographic and spectroscopic analysis (HPLC and ESI-IT-MSn). In the acute test, the EMe was administered orally and parenterally to rodents (mice and rats) for 14 days, at a dose of 2000 mg/kg. Subsequently, the repeated dose toxicity test was administered orally for 180 days at doses of 50, 300 or 1000 mg/kg. The HPLC assay revealed a high concentration of vitamin C (16.3%), and spectroscopic analyses pointed to the presence of five other polyphenolic compounds. In the acute test, the plant extract showed no apparent toxicity or lethality in rodents. The LD50 was estimated to be greater than 2000 mg/kg and falls into category 5 (low toxicity). In the repeated dose assay, there was no evidence of toxicity, and no differences were observed in water intake, food, weight development, or behavior of the animals in relation to the vehicle group (water). However, hematological and biochemical evaluations pointed out some nonconformities in the levels of cholesterol, leukocytes, and neutrophils of the male rats, but overall, these results did not reveal significant toxicity. Therefore, the Level of Unobserved Adverse Effects (NOAEL) was 1000 mg/kg. Together, the results suggest that the extract obtained from the fruits of M. emarginata does not present representative toxicity in rodents.
Assuntos
Frutas , Roedores , Ratos , Camundongos , Animais , Frutas/toxicidade , Frutas/química , Ácido Ascórbico , Rutina , Extratos Vegetais , Água , Testes de Toxicidade AgudaRESUMO
Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.
Estudos toxicológicos são essenciais para o desenvolvimento de novos medicamentos nas indústrias farmacêuticas, incluindo a preparação aiurvédica. Assim, o presente estudo tem como objetivo avaliar a toxicidade oral aguda e de dose repetida de 28 dias de grânulos de polierva (PHG) antiobesidade em ratos Sprague Dawley pelas diretrizes da OCDE nº 425 e 407, respectivamente. Em um estudo de toxicidade oral aguda, uma dose única de 2 g/kg de PHG foi administrada a ratos, e mortalidade, peso corporal e observações clínicas foram observadas por 14 dias. No entanto, no estudo de toxicidade oral subaguda, o PHG foi administrado oralmente em doses de 0,3, 0,5 e 1 g/kg diariamente por 28 dias em ratos. A ingestão alimentar e o peso corporal foram registrados semanalmente. No 29º dia, os ratos foram sacrificados e submetidos a análises hematológicas, bioquímicas, de urina, necropsia e histopatológica. Em um estudo de toxicidade oral aguda, nenhuma mortalidade, alterações comportamentais e toxicidade relacionadas ao tratamento foram encontradas ao longo de 14 dias. Da mesma forma, no estudo de toxicidade subaguda, não foram encontrados mortalidade e efeitos tóxicos em análises hematológicas, bioquímicas, de urina, necropsia e histopatológica em ratos durante 28 dias de tratamento com PHG. Com base nesses resultados, verificou-se que a DL50 de PHG era superior a 2 g/kg e o nível de efeitos adversos não observados (NOAEL) de PHG para ratos foi de 0,5 g/kg/dia. Assim, os grânulos poliervais antiobesidade apresentaram um bom perfil de segurança em estudos com animais e podem ser considerados um importante agente para o manejo clínico da obesidade.
Assuntos
Animais , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , ObesidadeRESUMO
Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 35 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.
Chrozophora tinctoria (L.) A.Juss. é uma planta anual herbácea, monoica, usada tradicionalmente para curar distúrbios gastrointestinais. O presente estudo foi realizado para encontrar os compostos bioativos por Cromatografia Gasosa-Espectrometria de Massa (GC-MS), a toxicidade aguda do potencial inibitório da acetilcolinesterase e a atividade emética presente na fração acetato de etila de Chrozophora tinctoria (EAFCT) e fração diclorometano de Chrozophora tinctoria (DCMFCT). Os compostos detectados em ambas as frações foram principalmente ácidos graxos, com cerca de sete compostos em EAFCT e 10 em DCMFCT. Estes incluíam compostos farmacologicamente ativos, como a imipramina, usada para tratar a depressão, ou éster metílico do ácido hexadecanoico, um antioxidante, nematicida, pesticida, hipocolesterolêmico, ácido 9,12,15-octadecatrienoico, éster etílico, (Z,Z,Z)- é usado como preventivo do câncer, antiartrítico, anti-histamínico, hepatoprotetor, inseticida, nematicida, ácido pentadecanoico, 14-metil-, éster metílico tem atividades antifúngicas, antimicrobianas e antioxidantes, ácido 10-octadecanoico, éster metílico tem a propriedade de diminuir o colesterol no sangue, antioxidante e antimicrobiano, o 1-Eicosanol é usado como antibacteriano, o 1-Hexadeceno possui atividades antibacteriana, antioxidante e antifúngica. Ambas as frações DCMFCT e EAFCT inibiram a atividade da acetilcolinesterase (AChE) com valores de IC50 de 10µg e 130µg, respectivamente. Ambas as frações foram consideradas tóxicas de maneira dose-dependente, induzindo vômitos a partir de 0,5g e letargia e mortalidade de 3g a 5g para cima. Ambas as frações combinadas com água destilada apresentaram atividade altamente emética. O aumento significativo no número de vômitos foi demonstrado pelo EAFCT mais água destilada, que são 7,50±1,29, 7,25±3,10 e 11,75±2,22 número de vômitos nas concentrações de 1g, 2g e 3g/kg, respectivamente, enquanto DCMFCT mais água destilada mostrou 5,25±2,22, 7,50±2,52 e 10,25±2,22 número de vômitos em 1g, 2g e 3g/kg, respectivamente. A droga padrão antiemética metoclopramida tem um impacto maior contra a emese induzida por ambas as frações do que o dimenidrinato. A metoclopramida diminui o número de vômitos causados ââpor EAFCT para 1,00±0,00, 2,00±0,00, 4,00±1,00 a 1g, 2g e 3g/kg, sequencialmente, enquanto o dimenidrinato diminui o número de vômitos para 1,33±0,58, 2,33±1,15, 4,33± 0,58 a 1g, 2g e 3g, respectivamente. Da mesma forma, a metocloprimida diminui o número de vômitos causados ââpor DcmCt de 5,25±2,22, 7,50±2,52, 10,25±2,22 para 1,33±0,58, 2,33±1,1, 4,33±0,58 nas concentrações de 1g, 2g e 3g/kg. O presente estudo é o primeiro relato documentado que valida cientificamente o uso folclórico de Chrozophora tinctoria como agente emético.
Assuntos
Plantas Medicinais/efeitos dos fármacos , Modelos Animais , Cromatografia Gasosa-Espectrometria de Massas , Antieméticos , AntinematódeosRESUMO
We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography-diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC-high-resolution mass spectrometry-DAD (HPLC-HRMS-DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD50) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC50) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis, respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis.
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Introducción. Alrededor de 3700 millones menores de 50 años con infección por VHS-1 y 491 millones de personas de 15 a 49 años cursan con infección por VHS-2 en el mundo; sus síntomas, vesículas o ulceras dolorosas reaparecen periódicamente. El tratamiento convencional disminuyó su efectividad en cepas resistentes e inmunodeprimidos. Alternativas terapéuticas con extractos de plantas medicinales y potencial antiviral, como Opuntia soehrensii Brito conocida como "ayrampù" en Bolivia, utiliza infusión de sus semillas como analgésico, antidiabético, hipotensor y febrífugo. En vapores por inhalación para afecciones respiratorias; como tintura tópica en lesiones dérmicas de viruela, sarampión y herpes labial. Objetivo. Evaluar la seguridad preclínica de un gel que contiene el extracto hidro-alcohólico de semillas de Opuntia soehrensii en diferentes dosis, aplicado en la mucosa vaginal de ratas Sprague Dawley. Material y métodos. Se ejecutaron protocolos de toxicidad aguda y subaguda para evaluar la respuesta sistémica, a través de marcadores bioquímicos y de comportamiento, y la respuesta local en mucosa vaginal, mediante estudios histopatológicos, en grupos de animales a los que se aplicó el gel con diferentes concentraciones del extracto de Opuntia soehrensii, comparados con un grupo control y otro que recibió solo el vehículo. Resultados. Se encontró que los indicadores sistémicos de comportamiento y ganancia de peso no mostraron diferencias entre grupos. Los indicadores hematológicos y bioquímicos mostraron resultados fisiológicamente esperados y sin cambios en los grupos de estudio. La citología expuso conservación del fenotipo celular para las fases del ciclo estral en todos los grupos. Los indicadores histológicos de reacción local e integridad celular se distribuyeron de igual manera en los todos los grupos. Conclusión. La aplicación de un gel de Opuntia soehrensii no muestra niveles apreciables de toxicidad local y sistémica, lo que permite recomendar la iniciación de estudios de aplicación clínica.
Introduction. Around 3.7 billion people under 50 years of age are infected with HSV-1 and 491 million people between the ages of 15 and 49 are infected with HSV-2 in the world; his symptoms, vesicles or painful ulcers recur periodically. Conventional treatment decreased its effectiveness in resistant and immunosuppressed strains. Therapeutic alternatives with extracts of medicinal plants and antiviral potential, such as Opuntia soehrensii Brito known as "ayrampù" in Bolivia, uses infusion of its seeds as an analgesic, antidiabetic, hypotensive and febrifuge. In vapors by inhalation for respiratory conditions; as a topical tincture in skin lesions of smallpox, measles and cold sores. Objectives . To evaluate the preclinical safety of a gel containing the hydroalcoholic extract of Opuntia soehrensii seeds in different doses, applied to the vaginal mucosa of Sprague Dawley rats. Material and Methods. Acute and sub-acute toxicity protocols were carried out to evaluate local response in the vaginal mucosa, through histo pathological studies, and systemic responses, through biochemical and behavioral markers, in groups of animals to which the gel with different concentrations of the extract of Opuntia soehrensii was applied, compared with a control group and another that received only the vehicle. Results. It was found that the histological indicators of local reaction and cell integrity were equally distributed in all groups. Cytology showed conservation of the cell phenotype for the phases of the estrous cycle in all groups. The systemic indicators of behavior and weight gain did not show differences between groups. Hematological and biochemical indicators showed results ranged in physiologic parameters, without changes in the study groups. Conclusion. The application of a gel from Opuntia soehrensii does not show appreciable levels of local and systemic toxicity, which makes it possible to recommend the initiation of clinical application studies.
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Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 µmol L-1, and 17.9 µg L-1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.
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In order to understand antidiabetic potential and toxicity, this study aimed to evaluate the acute toxicity and antidiabetic activity of ethanolic extract and ethyl acetate fraction obtained from Coutoubea spicata "nicolau" shoots. Chemical constituents and acute toxicity were investigated. In alloxan-induced diabetic rats, extract and fraction were tested at dose of 100 mg/kg, p.o. Body weight gain, glucose, lipid profile and oxidative stress markers in serum and tissues were determined. In vitro antioxidant activity was performed. Swertiamarin, gentiopicrin, deoxyloganic acid, clovin and robinin, and their p-coumaric ester were identified. Extract and fraction were classified as safe (category 5). In diabetic rats, Coutoubea spicata reduced glycaemia, which was accompanied by body weight recovery gain and attenuation in oxidative stress markers. Fraction showed scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS) radicals and reducing power higher than that of the extract. Extract and fraction of Coutoubea spicata didn't present significant toxicity and it can be investigated as a therapeutic alternative in diabetes.
Con el fin de conocer el potencial antidiabético y la toxicidad, este estudio tuvo como objetivo evaluar la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo obtenidos de los brotes de Coutoubea spicata "Nicolau". Se investigaron los componentes químicos y la toxicidad aguda. En ratas diabéticas inducidas por alloxan, se probaron el extracto y la fracción en dosis de 100 mg/kg, p.o. Se determinó el aumento de peso corporal, la glucosa, el perfil lipídico y los marcadores de estrés oxidativo en suero y tejidos. Se realizó una actividad antioxidante in vitro. Se identificaron la suertiamarina, la gentiopicrina, el ácido desoxilogánico, la clovina y la robinina, así como su éster p-cumárico. El extracto y la fracción se clasificaron como seguros (categoría 5). En ratas diabéticas, Coutoubea spicata redujo la glicemia, lo que se acompañó de una recuperación del peso corporal y de la atenuación de los marcadores de estrés oxidativo. La fracción mostró una actividad de barrido contra los radicales 1,1-difenil-2-picrilhidrazilo (DPPH) y 2,2'-azino-bis (ácido 3-etilbenzotiazolina-6-sulfónico) y un poder reductor superior al del extracto. El extracto y la fracción de Coutoubea spicata no presentaron una toxicidad significativa y pueden ser investigados como alternativa terapéutica en la diabetes.