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1.
Microb Pathog ; 192: 106711, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788810

RESUMEN

Medicinal plants have been widely used for their antimicrobial properties against various microorganisms. Arisaema dracontium a familiar medicinal plant, was analyzed and silver nanoparticles (AgNPs) were synthesized using extracts of different parts of its shoot including leaves and stem. Further, the antimicrobial activity of different solvent extracts such as ethyl acetate, n-hexane, ethanol, methanol, and chloroform extracts were analyzed. AgNPs were prepared using aqueous silver nitrate solution and assessed their antibacterial activity against multidrug-resistant (MDR) and Non-multidrug-resistant bacteria. The characterization of AgNPs was done by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), UV-visible spectroscopy, Fourier Transform Infrared (FTI), and X-ray Diffraction approaches. The leaf extract contained Tannins, Flavonoids, Terpenoids, and Steroids while Alkaloids, Saponins, and Glycosides were undetected. The stem extract contained Alkaloids, Tannins, Flavonoids, Saponins, Steroids, and Glycosides while Terpenoids were not observed. The AgNPs synthesized from stem and leaf extracts in the current study had spherical shapes and ranged in size from 1 to 50 nm and 20-500 nm respectively as were visible in TEM. The leaf extract-prepared AgNPs showed significantly higher activities i.e., 27.75 mm ± 0.86 against the MDR strains as compared to the stem-derived nanoparticles i.e., 24.33 ± 0.33 by comparing the zones of inhibitions which can be attributed to the differences in their phytochemical constituents. The acute toxicity assay confirmed that no mortality was noticed when the dosage was 100 mg per kg which confirms that the confirms that the AgNPs are not toxic when used in low quantities. It is concluded that leaf extract from A. dracontium could be used against pathogenic bacteria offering economic and health benefits compared to the chemical substances.


Asunto(s)
Antibacterianos , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Hojas de la Planta , Plata , Extractos Vegetales/farmacología , Extractos Vegetales/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Plata/farmacología , Plata/química , Hojas de la Planta/química , Bacterias/efectos de los fármacos , Difracción de Rayos X , Fitoquímicos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Plantas Medicinales/química , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Tallos de la Planta/química
2.
Toxicol Appl Pharmacol ; 492: 117098, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39251042

RESUMEN

Exposure to various chemicals found in the environment and in the context of drug development can cause acute toxicity. To provide an alternative to in vivo animal toxicity testing, the U.S. Tox21 consortium developed in vitro assays to test a library of approximately 10,000 drugs and environmental chemicals (Tox21 10 K compound library) in a quantitative high-throughput screening (qHTS) approach. In this study, we assessed the utility of Tox21 assay data in comparison with chemical structure information in predicting acute systemic toxicity. Prediction models were developed using four machine learning algorithms, namely Random Forest, Naïve Bayes, eXtreme Gradient Boosting, and Support Vector Machine, and their performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC). The chemical structure-based models as well as the Tox21 assay data demonstrated good predictive power for acute toxicity, achieving AUC-ROC values ranging from 0.83 to 0.93 and 0.73 to 0.79, respectively. We applied the models to predict the acute toxicity potential of the compounds in the Tox21 10 K compound library, most of which were found to be non-toxic. In addition, we identified the Tox21 assays that contributed the most to acute toxicity prediction, such as acetylcholinesterase (AChE) inhibition and p53 induction. Chemical features including organophosphates and carbamates were also identified to be significantly associated with acute toxicity. In conclusion, this study underscores the utility of in vitro assay data in predicting acute toxicity.

3.
Microb Cell Fact ; 23(1): 216, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080612

RESUMEN

BACKGROUND: D-psicose 3-epimerase (DPEase) is a potential catalytic enzyme for D-psicose production. D-psicose, also known as D-allulose, is a low-calorie sweetener that has gained considerable attention as a healthy alternative sweetener due to its notable physicochemical properties. This research focused on an in-depth investigation of the expression of the constructed DPEase gene from Agrobacterium tumefaciens in Escherichia coli for D-psicose synthesis. Experimentally, this research created the recombinant enzyme, explored the optimization of gene expression systems and protein purification strategies, investigated the enzymatic characterization, and then optimized the D-psicose production. Finally, the produced D-psicose syrup underwent acute toxicity evaluation to provide scientific evidence supporting its safety. RESULTS: The optimization of DPEase expression involved the utilization of Mn2+ as a cofactor, fine-tuning isopropyl ß-D-1-thiogalactopyranoside induction, and controlling the induction temperature. The purification process was strategically designed by a nickel column and an elution buffer containing 200 mM imidazole, resulting in purified DPEase with a notable 21.03-fold increase in specific activity compared to the crude extract. The optimum D-psicose conversion conditions were at pH 7.5 and 55 °C with a final concentration of 10 mM Mn2+ addition using purified DPEase to achieve the highest D-psicose concentration of 5.60% (w/v) using 25% (w/v) of fructose concentration with a conversion rate of 22.42%. Kinetic parameters of the purified DPEase were Vmax and Km values of 28.01 mM/min and 110 mM, respectively, which demonstrated the high substrate affinity and efficiency of DPEase conversion by the binding site of the fructose-DPEase-Mn2+ structure. Strategies for maintaining stability of DPEase activity were glycerol addition and storage at -20 °C. Based on the results from the acute toxicity study, there was no toxicity to rats, supporting the safety of the mixed D-fructose-D-psicose syrup produced using recombinant DPEase. CONCLUSIONS: These findings have direct and practical implications for the industrial-scale production of D-psicose, a valuable rare sugar with a broad range of applications in the food and pharmaceutical industries. This research should advance the understanding of DPEase biocatalysis and offers a roadmap for the successful scale-up production of rare sugars, opening new avenues for their utilization in various industrial processes.


Asunto(s)
Escherichia coli , Fructosa , Proteínas Recombinantes , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Fructosa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Agrobacterium tumefaciens , Carbohidrato Epimerasas/genética , Carbohidrato Epimerasas/metabolismo , Carbohidrato Epimerasas/aislamiento & purificación , Animales , Racemasas y Epimerasas/metabolismo , Racemasas y Epimerasas/genética , Ratas , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
4.
J Chem Ecol ; 50(3-4): 185-196, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38441803

RESUMEN

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.


Asunto(s)
Glicósidos , Pepinos de Mar , Triterpenos , Vísceras , Pez Cebra , Animales , Pez Cebra/fisiología , Glicósidos/química , Glicósidos/toxicidad , Glicósidos/metabolismo , Vísceras/química , Vísceras/efectos de los fármacos , Triterpenos/química , Triterpenos/farmacología , Triterpenos/metabolismo , Pepinos de Mar/química , Embrión no Mamífero/efectos de los fármacos , Toxinas Marinas/toxicidad , Toxinas Marinas/química
5.
Pediatr Nephrol ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39347990

RESUMEN

Despite its widespread use in patients undergoing organ transplantation or managing nephrotic syndrome, there is a lack of literature on the acute toxicity of cyclosporine A (CsA). This report presents a case of acute CsA toxicity resulting from an accidental overdose in a 2-year-old boy with steroid dependent nephrotic syndrome. Remarkably, despite a tenfold overdose and elevated trough levels, the patient remained asymptomatic, and the CsA trough level normalized within 48 h with rapid intervention, including discontinuation of CsA, intravenous hydration, and cytochrome P450 induction. This case emphasizes the critical importance of prompt and appropriate management to prevent serious consequences in such scenarios.

6.
Environ Res ; 242: 117767, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38029826

RESUMEN

The anti-dermatophytic (Proteus vulgaris, Klebsiella pneumoniae, Enterobacter aerogenes, Propionibacterium acnes, Staphylococcus aureus, and Streptococcus pyogenes) and nephroprotective activities of methanol and aqueous extracts obtained from Lannea coromandelica fruit were investigated through in-vitro (agar well diffusion method) and in-vivo (animal model) study. The methanol extract showed considerable antibacterial activity against selective bacterial pathogens at increased concentration (15.0 mg mL-1) in the following order P. vulgaris (35.2 ± 1.6 mm) > E. aerogenes (32.1 ± 2.1 mm) > K. pneumoniae (29.3±2 mm) > P. acnes (28.2 ± 2.4 mm) > S. aureus (25.5 ± 2.4 mm) > S. pyogenes (24.3 ± 2.1 mm) than aqueous extract. The MIC values of this methanol and aqueous extract was found as 2.5-7.5 mg mL-1 and 5.0 to 1.0 mg mL-1 respectively. Different treatment sets (A-E) on a rat-based animal model study revealed that the methanol extract has excellent antioxidant and nephroprotective activity, as well as favorable effects on essential biochemical substances involved in active metabolic activities. As demonstrated by histopathological and microscopic examination, the biologically active chemical present in methanol extract had a positive effect on serum markers, enzyme, and non-enzyme-based antioxidant activities, as well as lowering the toxicity caused by EG in the rat (as nephroprotective activity) renal cells.


Asunto(s)
Anacardiaceae , Antioxidantes , Ratas , Animales , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Metanol/farmacología , Frutas , Staphylococcus aureus , Pruebas de Sensibilidad Microbiana , Antibacterianos/toxicidad , Antibacterianos/química , Agua
7.
Arch Toxicol ; 98(4): 1135-1149, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38446233

RESUMEN

A-series agent A-234 belongs to a new generation of nerve agents. The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. In this article, we first assessed A-234 stability in neutral pH for subsequent experiments. Then, we determined its inhibitory potential towards human recombinant acetylcholinesterase (HssAChE; EC 3.1.1.7) and butyrylcholinesterase (HssBChE; EC 3.1.1.8), the ability of HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime to reactivate inhibited cholinesterases (ChEs), its toxicity in rats and therapeutic effects of different antidotal approaches. Finally, we utilized molecular dynamics to explain our findings. The results of spontaneous A-234 hydrolysis showed a slow process with a reaction rate displaying a triphasic course during the first 72 h (the residual concentration 86.2%). A-234 was found to be a potent inhibitor of both human ChEs (HssAChE IC50 = 0.101 ± 0.003 µM and HssBChE IC50 = 0.036 ± 0.002 µM), whereas the five marketed oximes have negligible reactivation ability toward A-234-inhibited HssAChE and HssBChE. The acute toxicity of A-234 is comparable to that of VX and in the context of therapy, atropine and diazepam effectively mitigate A-234 lethality. Even though oxime administration may induce minor improvements, selected oximes (HI-6 and methoxime) do not reactivate ChEs in vivo. Molecular dynamics implies that all marketed oximes are weak nucleophiles, which may explain the failure to reactivate the A-234 phosphorus-serine oxygen bond characterized by low partial charge, in particular, HI-6 and trimedoxime oxime oxygen may not be able to effectively approach the A-234 phosphorus, while pralidoxime displayed low interaction energy. This study is the first to provide essential experimental preclinical data on the A-234 compound.


Asunto(s)
Reactivadores de la Colinesterasa , Compuestos de Pralidoxima , Taurina/análogos & derivados , Ratas , Humanos , Animales , Reactivadores de la Colinesterasa/farmacología , Trimedoxima/farmacología , Butirilcolinesterasa , Acetilcolinesterasa , Oximas/farmacología , Compuestos de Piridinio/farmacología , Antídotos/farmacología , Inhibidores de la Colinesterasa/toxicidad , Fósforo , Oxígeno
8.
Arch Toxicol ; 98(1): 267-275, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38051368

RESUMEN

Nerve agents are organophosphate chemical warfare agents that exert their toxic effects by irreversibly inhibiting acetylcholinesterase, affecting the breakdown of the neurotransmitter acetylcholine in the synaptic cleft. Due to the risk of exposure to dangerous nerve agents and for animal welfare reasons, in silico methods have been used to assess acute toxicity safely. The next-generation risk assessment (NGRA) is a new approach for predicting toxicological parameters that can meet modern requirements for toxicological research. The present study explains the acute toxicity of the examined V-series nerve agents (n = 9) using QSAR models. Toxicity Estimation Software Tool (ver. 4.2.1 and ver. 5.1.2), QSAR Toolbox (ver. 4.6), and ProTox-II browser application were used to predict the median lethal dose. The Simplified Molecular Input Line Entry Specification (SMILES) was the input data source. The results indicate that the most deadly V-agents were VX and VM, followed by structural VX analogues: RVX and CVX. The least toxic turned out to be V-sub x and Substance 100A. In silico methods for predicting various parameters are crucial for filling data gaps ahead of experimental research and preparing for the upcoming use of nerve agents.


Asunto(s)
Sustancias para la Guerra Química , Agentes Nerviosos , Compuestos Organotiofosforados , Animales , Sustancias para la Guerra Química/toxicidad , Sustancias para la Guerra Química/química , Agentes Nerviosos/toxicidad , Agentes Nerviosos/química , Acetilcolinesterasa/metabolismo , Compuestos Organotiofosforados/toxicidad
9.
Arch Toxicol ; 98(6): 1809-1825, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38493428

RESUMEN

The idea of this study was the estimation of the theoretical acute toxicity (t-LD50, rat, oral dose) of organophosphorus-based chemical warfare agents from the G-series (n = 12) using different in silico methods. Initially identified in Germany, the G-type nerve agents include potent compounds such as tabun, sarin, and soman. Despite their historical significance, there is a noticeable gap in acute toxicity data for these agents. This study employs qualitative (STopTox and AdmetSAR) and quantitative (TEST; CATMoS; ProTox-II and QSAR Toolbox) in silico methods to predict LD50 values, offering an ethical alternative to animal testing. Additionally, we conducted quantitative extrapolation from animals, and the results of qualitative tests confirmed the acute toxicity potential of these substances and enabled the identification of toxicophoric groups. According to our estimations, the most lethal agents within this category were GV, soman (GD), sarin (GB), thiosarin (GBS), and chlorosarin (GC), with t-LD50 values (oral administration, extrapolated from rat to human) of 0.05 mg/kg bw, 0.08 mg/kg bw, 0.12 mg/kg bw, 0.15 mg/kg bw, and 0.17 mg/kg bw, respectively. On the contrary, compounds with a cycloalkane attached to the phospho-oxygen linkage, specifically methyl cyclosarin and cyclosarin, were found to be the least toxic, with values of 2.28 mg/kg bw and 3.03 mg/kg bw. The findings aim to fill the knowledge gap regarding the acute toxicity of these agents, highlighting the need for modern toxicological methods that align with ethical considerations, next-generation risk assessment (NGRA) and the 3Rs (replacement, reduction and refinement) principles.


Asunto(s)
Sustancias para la Guerra Química , Simulación por Computador , Compuestos Organofosforados , Relación Estructura-Actividad Cuantitativa , Sustancias para la Guerra Química/toxicidad , Animales , Dosificación Letal Mediana , Compuestos Organofosforados/toxicidad , Ratas , Administración Oral , Sarín/toxicidad , Pruebas de Toxicidad Aguda/métodos , Soman/toxicidad , Medición de Riesgo/métodos
10.
Arch Toxicol ; 98(5): 1469-1483, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38441627

RESUMEN

The emergence of Novichok agents, potent organophosphorus nerve agents, has spurred the demand for advanced analytical methods and toxicity assessments as a result of their involvement in high-profile incidents. This study focuses on the degradation products of Novichok agents, particularly their potential toxic effects on biological systems. Traditional in vivo methods for toxicity evaluation face ethical and practical constraints, prompting a shift toward in silico toxicology research. In this context, we conducted a comprehensive qualitative and quantitative analysis of acute oral toxicity (AOT) for Novichok degradation products, using various in silico methods, including TEST, CATMoS, ProTox-II, ADMETlab, ACD/Labs Percepta, and QSAR Toolbox. Adopting these methodologies aligns with the 3Rs principle, emphasising Replacement, Reduction, and Refinement in the realm of toxicological studies. Qualitative assessments with STopTox and admetSAR revealed toxic profiles for all degradation products, with predicted toxicophores highlighting structural features responsible for toxicity. Quantitative predictions yielded varied estimates of acute oral toxicity, with the most toxic degradation products being EOPAA, MOPGA, MOPAA, MPGA, EOPGA, and MPAA, respectively. Structural modifications common to all examined hydrolytic degradation products involve substituting the fluorine atom with a hydroxyl group, imparting consequential effects on toxicity. The need for sophisticated analytical techniques for identifying and quantifying Novichok degradation products is underscored due to their inherent reactivity. This study represents a crucial step in unravelling the complexities of Novichok toxicity, highlighting the ongoing need for research into its degradation processes to refine analytical methodologies and fortify readiness against potential threats.


Asunto(s)
Agentes Nerviosos , Organofosfatos
11.
J Toxicol Environ Health A ; 87(14): 592-603, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38712866

RESUMEN

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.


Asunto(s)
Antioxidantes , Extractos Vegetales , Granada (Fruta) , Animales , Ratones , Antioxidantes/farmacología , Femenino , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Granada (Fruta)/química , Lectinas/toxicidad , Pruebas de Mutagenicidad , Daño del ADN/efectos de los fármacos , Pruebas de Toxicidad Aguda
12.
BMC Public Health ; 24(1): 1641, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38898445

RESUMEN

OBJECTIVES: In Canada, substance-related accidental acute toxicity deaths (AATDs) continue to rise at the national and sub-national levels. However, it is unknown if, where, when, and to what degree AATDs cluster in space, time, and space-time across the country. The objectives of this study were to 1) assess for clusters of AATDs that occurred in Canada during 2016 and 2017 at the national and provincial/territorial (P/T) levels, and 2) examine the substance types detected in AATD cases within each cluster. METHODS: Two years of person-level data on AATDs were abstracted from coroner and medical examiner files using a standardized data collection tool, including the decedent's postal code and municipality information on the places of residence, acute toxicity (AT) event, and death, and the substances detected in the death. Data were combined with Canadian census information to create choropleth maps depicting AATD rates by census division. Spatial scan statistics were used to build Poisson models to identify clusters of high rates (p < 0.05) of AATDs at the national and P/T levels in space, time, and space-time over the study period. AATD cases within clusters were further examined for substance types most present in each cluster. RESULTS: Eight clusters in five regions of Canada at the national level and 24 clusters in 15 regions at the P/T level were identified, highlighting where AATDs occurred at far higher rates than the rest of the country. The risk ratios of identified clusters ranged from 1.28 to 9.62. Substances detected in clusters varied by region and time, however, opioids, stimulants, and alcohol were typically the most commonly detected substances within clusters. CONCLUSION: Our findings are the first in Canada to reveal the geographic disparities in AATDs at national and P/T levels using spatial scan statistics. Rates associated with substance types within each cluster highlight which substance types were most detected in the identified regions. Findings may be used to guide intervention/program planning and provide a picture of the 2016 and 2017 context that can be used for comparisons of the geographic distribution of AATDs and substances with different time periods.


Asunto(s)
Análisis Espacio-Temporal , Humanos , Canadá/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/mortalidad , Análisis por Conglomerados , Anciano
13.
Regul Toxicol Pharmacol ; 146: 105542, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38070762

RESUMEN

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.


Asunto(s)
Diabetes Mellitus , Medicamentos Herbarios Chinos , Lignanos , Ratas , Humanos , Animales , Ratas Sprague-Dawley , Preparaciones Farmacéuticas , Diabetes Mellitus/tratamiento farmacológico , Lignanos/toxicidad
14.
Regul Toxicol Pharmacol ; 151: 105674, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38968966

RESUMEN

We examined the need for new in vivo avian toxicity testing for three common industrial chemicals (1,2 dichloropropane, 1,1,2-trichloroethane and triphenyl phosphate) based on estimated avian exposures using fugacity and multimedia fate models for current conditions of use compared to hazard information including existing in vivo test data for the chemicals and analogs, interspecies correlation estimates and results from hundreds of acute avian dietary toxicity studies. The data indicated that acute avian toxicity is not likely to be observed below 10 ppm in the diet for any chemical with the exception of those with a specific mode of toxic action. Modeling indicated low exposure potential for terrestrial birds to any of the three chemicals, with estimated dietary concentration of less than 0.001 ppm. Despite uncertainty associated with the underlying data sources, the four order of magnitude gap between potential exposure and a minimum hazard threshold suggests that additional avian in vivo testing would not generate valuable data. However, a weight of evidence approach for integrating data is necessary to engender greater confidence among government decision-makers in cases where data from a particular in vivo study is not expected to improve risk decision-making and an existing data gap can remain unfilled.


Asunto(s)
Aves , Medición de Riesgo , Animales , Estados Unidos , Toma de Decisiones , Pruebas de Toxicidad/métodos , Humanos
15.
Ecotoxicol Environ Saf ; 269: 115824, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38096595

RESUMEN

Eisenia fetida is recognised as advantageous model species in ecotoxicological and regeneration investigations. The intensive utilization of carbamate pesticides (CARs) imposes heavy residue burdens and grave hazards on edaphic environments as well as soil fauna therein. However, precise mechanisms whereby the specific CAR exerted toxic effects on earthworms remain largely elusive, notably from regenerative perspective. Herein, acute responses and regenerative toxicity of two carbamates (metolcarb, MEB and fenoxycarb, FEB) against E. fetida were dissected using biochemical, histological as well as molecular approaches following OECD guidelines at the cellular, tissue and organismal level. The acute toxicity data implied that MEB/FEB were very toxic/medium to extremely toxic, respectively in filter paper contact test and low to medium toxic/low toxic, respectively in artificial soil test. Chronic exposure to MEB and FEB at sublethal concentrations significantly mitigated the soluble protein content, protein abundance while enhanced the protein carbonylation level. Moreover, severely retarded posterior renewal of amputated earthworms was noticed in MEB and FEB treatments relative to the control group, with pronouncedly compromised morphology, dwindling segments and elevated cell apoptosis of blastema tissues, which were mediated by the rising Sox2 and decreasing TCTP levels. Taken together, these findings not only presented baseline toxicity cues for MEB and FEB exposure against earthworms, but also yielded mechanistic insights into regenerative toxicity upon CAR exposure, further contributing to the environmental risk assessment and benchmark formulation of agrochemical pollution in terrestrial ecosystem.


Asunto(s)
Oligoquetos , Contaminantes del Suelo , Animales , Carbamatos/metabolismo , Ecosistema , Contaminantes del Suelo/análisis , Suelo/química
16.
Ecotoxicol Environ Saf ; 287: 117261, 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39476651

RESUMEN

Due to the substantial production and use of antibiotics, they inevitably remain in aquatic environments, posing a serious threat to aquatic ecosystems. However, there are currently no criteria of antibiotics for ecological risk in the water environment. In the present study, three types of antibiotics (tetracyclines, sulfonamides and quinolones) that are often detected in water environments were investigated. Toxicity data regarding bacteria, algae, plants, invertebrates and vertebrates were selected, and the species sensitivity distribution was used to obtain the ecological risk criteria of antibiotics to aquatic organisms. Animals are the least sensitive to antibiotics. The overall toxicity of antibiotics is most sensitive to bacteria and cyanobacteria, followed by green algae and plants. The recommended ecological criteria for tetracyclines, quinolones, and sulfonamides are 22, 17, and 94 µg/L, respectively. Ofloxacin needs to be used with caution because it has a small acute predicted no-effect concentration (PNEC) of 0.6 µg/L. The ecological risk criterion for chronic toxicity of total antibiotics was determined to be 1.4 µg/L. The PNECs measured for the quinolone, tetracycline, and sulfonamide antibiotics were 0.5, 2.2, and 2.4 µg/L, respectively. Norfloxacin had the highest chronic toxicity zone of 353, indicating that chronic poisoning is most likely to occur. Moreover, there was an exponential correlation between acute PNEC and chronic PNEC. In addition, a quantitative structure-activity relationship model was constructed for acute ecological risk criteria of antibiotics to aquatic organisms. These findings can expand the ecological risk threshold data on the effects of antibiotics on aquatic organisms, and provide a theoretical basis for the environmental risk assessment of antibiotics.

17.
Ecotoxicol Environ Saf ; 274: 116223, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38493704

RESUMEN

Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.


Asunto(s)
Compuestos Heterocíclicos de 4 o más Anillos , Lactonas , Oligoquetos , Contaminantes del Suelo , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Ecosistema , Simulación del Acoplamiento Molecular , Glutatión Transferasa/metabolismo , Contaminantes del Suelo/metabolismo , Superóxido Dismutasa/metabolismo , Suelo/química , Malondialdehído/metabolismo , Estrés Oxidativo
18.
Ecotoxicology ; 33(7): 750-761, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39026048

RESUMEN

The use of some organophosphate insecticides is restricted or even banned in paddy fields due to their high toxicity to aquatic organisms. The aim of this study is to elucidate the main pathways and target organs of organophosphate insecticide toxicity to fish exposed via different routes by integrating histopathological and biochemical techniques. Using malathion as the model drug, when the dosage is 20-60 mg/L, the toxicity of whole body and head immersion drugs to zebrafish is much higher than that of trunk immersion drugs. A dose of 21.06-190.44 mg/kg of malathion feed was fed to adult zebrafish. Although the dosage was already high, no obvious toxicity was observed. Therefore, we believe that the drug mainly enters the fish body through the gills. When exposed to a drug solution of 20 mg/L and 60 mg/L, the fish showed significant neurological behavioral abnormalities, and the pathological damage to key organs and brain tissue was the most severe, showing obvious vacuolization and the highest residual amount (8.72-47.78 mg/L). The activity of acetylcholinesterase was the most inhibited (54.69-74.68%). Therefore, brain tissue is the key toxic target organ of malathion in fish. In addition, we compared the bioaccumulation effects of different water-soluble organophosphorus insecticides in fish and their toxic effects. We found that the higher the water solubility of organophosphorus insecticides, the lower their toxicity to fish.


Asunto(s)
Bioacumulación , Insecticidas , Malatión , Contaminantes Químicos del Agua , Pez Cebra , Animales , Insecticidas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Malatión/toxicidad , Solubilidad , Pruebas de Toxicidad Aguda , Acetilcolinesterasa/metabolismo , Encéfalo/efectos de los fármacos
19.
Ecotoxicology ; 33(9): 1074-1085, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39215898

RESUMEN

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.


Asunto(s)
Crustáceos , Monitoreo del Ambiente , Contaminantes Químicos del Agua , Medición de Riesgo , Contaminantes Químicos del Agua/toxicidad , Animales , Crustáceos/efectos de los fármacos , Brasil , Metales Pesados/toxicidad , Metales/toxicidad , Pruebas de Toxicidad
20.
Luminescence ; 39(3): e4721, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38501275

RESUMEN

Luminescent bacteria-based biosensors are widely used for fast and sensitive monitoring of food safety, water quality, and other environmental pollutions. Recent advancements in biomedical engineering technology have led to improved portability, integration, and intelligence of these biotoxicity assays. Moreover, genetic engineering has played a significant role in the development of recombinant luminescent bacterial biosensors, enhancing both detection accuracy and sensitivity. This review provides an overview of recent advances in the development and applications of novel luminescent bacteria-based biosensors, and future perspectives and challenges in the cutting-edge research, market translation, and practical applications of luminescent bacterial biosensing are discussed.


Asunto(s)
Bacterias , Técnicas Biosensibles , Bacterias/genética , Luminiscencia
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