chronic toxicity

慢性毒性
  • 文章类型: Journal Article
    全氟烷基和多氟烷基物质(PFAS)在水生环境中受到严重污染,并可能危害水生生物。由于直接对濒危(T&E)物种进行毒性实验的局限性,它们的毒性数据很少,阻碍准确的风险评估。计算毒理学的发展使评估污染物对T&E鱼类的风险成为可能。这项研究创新性地结合了机器学习模型,包括随机森林(RF),人工神经网络(ANN),和XGBoost,和QSAR-ICE模型预测PFAS对T&E鱼类的慢性发育毒性数据。其中,XGBoost模型表现出卓越的性能,训练集和测试集的R2为0.95和0.81,分别。内部和外部验证进一步证实了XGBoost模子的鲁棒性和靠得住性。随后,它被用来预测长江七种优先PFAS对T&E鱼类的慢性发育毒性数据。酸性科鱼类(例如,达布兰丝鱼和中华民国丝鱼)对PFAS表现出很高的敏感性,可能是由于他们独特的生活方式和生理特点。基于这些数据,计算了单个PFAS的预测无效应浓度(PNEC),并评估了长江T&E鱼类的风险。结果表明,PFASs对T&E鱼类的风险较低(3.85×10-9~8.20×10-4),以全氟己酸(PFHxA)和全氟辛酸(PFOA)为高危污染物。河流中下游的风险高于上游。这项研究为获取慢性毒性数据和进行T&E物种的风险评估提供了一种新的方法,在全球范围内推进对T&E物种的保护。
    Per- and polyfluoroalkyl substances (PFASs) are severely polluted in aquatic environments and can harm aquatic organisms. Due to the limitation of conducting toxicity experiments directly on threatened and endangered (T&E) species, their toxicity data is scarce, hindering accurate risk assessments. The development of computational toxicology makes it possible to assess the risk of pollutants to T&E fishes. This study innovatively combined machine learning models, including random forest (RF), artificial neural network (ANN), and XGBoost, and the QSAR-ICE model to predict chronic developmental toxicity data of PFASs to T&E fishes. Among these, the XGBoost model exhibited superior performance, with R2 of 0.95 and 0.81 for the training and testing sets, respectively. Internal and external validation further confirmed that the XGBoost model is robust and reliable. Subsequently, it was used to predict chronic developmental toxicity data for seven priority PFASs to T&E fishes in the Yangtze River. Acipenseridae fishes (e.g., Acipenser dabryanus and Acipenser sinensis) showed high sensitivity to PFASs, possibly due to their unique lifestyle and physiological characteristics. Based on these data, the predicted no-effect concentration (PNEC) of individual PFASs was calculated, and the risk for T&E fishes in the Yangtze River was assessed. The results indicated that the risk of PFASs to T&E fishes is low (3.85×10-9∼8.20×10-4), with perfluorohexanoic acid (PFHxA) and perfluorooctanoic acid (PFOA) as the high-risk pollutants. The risk in the middle and lower reaches of the river is higher than in the upper reaches. This study provides a new approach for obtaining chronic toxicity data and conducting risk assessments for T&E species, advancing the protection of T&E species worldwide.
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  • 文章类型: Journal Article
    利用上流式厌氧反应器对工业废水进行厌氧处理是一种扩展趋势,由于其高效率和沼气生产潜力,但是由于废水的复杂性和毒性,其在某些部门的实施受到限制。在这项研究中,已经在实验室和中试规模上研究了两级膨胀颗粒污泥床(EGSB)反应器系统,用于处理来自石化行业的复杂和有毒的实际废水。包括有机负荷率(OLR)在内的不同运行参数的影响,水力停留时间(HRT)和进水特性对COD去除和沼气的产生和组成进行了研究。此外,生物质比产甲烷活性(SMA)和废水毒性已被评估后长期运行。已确定24h的最佳总HRT,导致总COD和SO42-去除率为56.30±5.25%和31.68±14.71%,分别,在试点规模,平均沼气产量为93.47±34.92NL/天,CH4含量为67.01±10.23%,H2S为5210.11±6802.27ppmv。SMA和毒性测试已证实废水对厌氧生物质的抑制作用和毒性作用,在未适应的厌氧接种物中平均最大抑制作用为65.34%,而慢性毒性在运行600天后使SMA降低了一个数量级。这项研究证明了使用EGSB反应器在0.97-1.74gCOD/L/天OLR范围内对该废水进行厌氧处理的可行性。尽管如此,由于废水对厌氧生物质的慢性毒性,因此长期运行需要定期再培养。实践要点:两级EGSB反应器系统已在实验室和中试规模下运行,以处理复杂和有毒的石化废水。24h的最佳总HRT导致平均COD去除率为40%至60%。已经进行了SMA和毒性测试来研究长期适应,检测到一个数量级的活动消耗。
    Anaerobic treatment of industrial wastewater using upflow anaerobic reactors is an extended trend due to its high efficiency and biogas production potential, but its implementation in some sectors is limited due to the complexity and toxicity of the wastewaters. In this study, a two-stage expanded granular sludge bed (EGSB) reactors system has been investigated at both bench and pilot scale for the treatment of complex and toxic real wastewater from a petrochemical industry. The effect of different operational parameters including organic loading rate (OLR), hydraulic retention time (HRT) and influent characteristics over COD removal and biogas production and composition have been studied. Additionally, biomass specific methanogenic activity (SMA) and wastewater toxicity have been evaluated after long-term operation. Optimum total HRT of 24 h has been determined resulting in total COD and SO4 2- removal of 56.30 ± 5.25% and 31.68 ± 14.71%, respectively, at pilot scale, and average biogas production of 93.47 ± 34.92 NL/day with 67.01 ± 10.23 %CH4 content and 5210.11 ± 6802.27 ppmv of H2S. SMA and toxicity tests have confirmed inhibitory and toxic effects of wastewater over anaerobic biomass with average maximum inhibition of 65.34% in the unacclimated anaerobic inoculum while chronic toxicity produced a decrease of an order of magnitude in SMA after 600 days of operation. This study demonstrates the feasibility of applying an anaerobic treatment to this wastewater using EGSB reactors between a 0.97-1.74 gCOD/L/day OLR range. Nonetheless, periodic reinoculation would be necessary for long-term operation due to chronic toxicity of the wastewater exerted on the anaerobic biomass. PRACTITIONER POINTS: A two-stage EGSB reactors system has been operated at bench and pilot scale to treat complex and toxic petrochemical wastewater. Optimal total HRT of 24 h resulted in average COD removal ranging from 40% to 60%. SMA and toxicity tests have been performed to study long-term acclimation, detecting an activity depletion of an order of magnitude.
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  • 文章类型: Journal Article
    微塑料(MPs)对水生动物的毒性与所含添加剂的存在和释放动力学密切相关,因为大多数塑料制品含有各种添加剂。然而,添加剂的发生和释放之间的关系,其单独或联合毒性尚不清楚。在这项研究中,四溴双酚A(TBBPA,一种常见的具有内分泌干扰作用的阻燃剂)在聚苯乙烯(PS)MPs中,和TBBPA和含有TBBPA的MP的长期(60天)毒性(在0%的剂量下,1%,10%,w/w)对非洲爪狼t进行了调查。仅暴露于10μg/L的TBBPA是最有毒的,而TBBPA在MPs中的封装通过抑制TBBPA的快速和广泛释放而显着延迟了其对t的致死毒性。与单独的TBBPA相比,单独的PSMPs和含有10%TBBPA的MPs表现出延迟的存活毒性,而含有1%TBBPA的PSMPs没有表现出这种作用,但抑制了生长。这些发现表明,由于有毒添加剂的封装控制缓慢释放,因此慢性毒性评估应基于长期(数月甚至数年)暴露实验。
    The toxicity of microplastics (MPs) to aquatic animals is closely related to the presence and release kinetics of contained additives, as most plastic products contain various additives. However, the relationship between the occurrence and release of additives from MPs, and their individual or combined toxicity remains unclear. In this study, the nanoscale distribution and release of tetrabromobisphenol A (TBBPA, a common flame retardant with endocrine-disrupting effect) in polystyrene (PS) MPs, and the long-term (60 days) toxicity of TBBPA and MPs containing TBBPA (at doses of 0 %, 1 %, 10 %, w/w) to Xenopus tropicalis tadpoles were investigated. Exposure to 10 μg/L TBBPA alone was the most toxics, while the encapsulation of TBBPA in MPs significantly delayed its lethal toxicity to tadpoles by inhibiting the rapid and extensive release of TBBPA. PS MPs alone and MPs containing 10 % TBBPA exhibited delayed survival toxicity compared to TBBPA alone, whereas PS MPs containing 1 % TBBPA did not show this effect but inhibited growth. These findings suggest that chronic toxicity assessments should be based on long-term (months or even years) exposure experiments due to the encapsulation-controlled slow release of toxic additives.
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  • 文章类型: Journal Article
    生物通常暴露于水生环境中新兴污染物的混合物。由于它们的广泛使用和环境相关性,研究了阿奇霉素(AZT)和伊维菌素(IVM)对淡水轮虫Lecanepapuana和euryhaline轮虫Proales的单独和联合作用。与AZT相比,轮虫对IVM的敏感性更高。IVM和AZT对木瓜乳杆菌和木瓜的LC50值分别为0.163和0.172mg/L,13.52和20.00毫克/升,分别。人口增长率,在慢性毒性试验中评估,对两种毒物浓度的增加做出了负面反应,无论是单独或组合。我们的结果揭示了两种不同的组合毒性反应:在淡水轮虫中具有很强的协同作用,而AZT-IVM混合物在欧陆轮虫中具有明显的拮抗作用。
    Organisms are usually exposed to mixtures of emerging pollutants in aquatic environments. Due to their widespread use and environmental relevance, the individual and combined effects of the drugs azithromycin (AZT) and ivermectin (IVM) on the freshwater rotifer Lecane papuana and the euryhaline rotifer Proales similis were investigated. Rotifers showed greater sensitivity to IVM compared to AZT. The LC50 values of IVM and AZT for L. papuana and P. similis were 0.163 and 0.172 mg/L, and 13.52 and 20.00 mg/L, respectively. Population growth rates, assessed in chronic toxicity assays, responded negatively to increasing concentrations of both toxicants, either individually or in combination. Our results revealed two distinct combined toxicity responses: a strong synergistic effect in the freshwater rotifer and a marked antagonistic impact of the AZT-IVM mixtures in the euryhaline rotifer.
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  • 文章类型: Journal Article
    多环芳烃(PAHs)产生于石油的不完全燃烧,煤炭,汽油,具有亲脂性,有利于它们的广泛分布和持久性。由于它们的生化属性,多环芳烃可以在动物组织中积累,可能引起诱变和致癌作用。自工业革命以来,环境中的PAH浓度上升,湖泊的沉积物含量为0.159至33,090μg/kg。尽管急性毒性研究表明对淡水生物有不利影响,与其他污染物的长期影响和协同相互作用在很大程度上仍未被探索。这项研究调查了菲(PHE)的影响,在水生环境中发现的一种突出的PAH,关于大型水蚤,在全球淡水生态系统中具有重要生态意义的物种,既是化学污染的前哨物种,又是淡水水生生态系统中的基石生物。利用D.magna的休眠,跨越几十年甚至几个世纪,我们将具有不同化学污染物暴露史的菌株暴露于环境相关浓度的PHE。最初,急性暴露实验是根据OECD指南对16株水蚤进行的,揭示了急性毒性反应的实质性变化,菌株对化学污染物的毒性最低。利用来自急性暴露的中值效应浓度EC10,我们评估了慢性PHE暴露对16种菌株的生活史特征和生态终点的影响.为了阐明历史上暴露于其他环境应激源如何调节PHE的毒性,利用了从湖中复活的D.magna的时间种群,该湖具有悠久的世纪环境影响历史。我们的发现表明,PHE暴露会导致发育失败,延迟性成熟,并减少水蚤的成年大小。与幼稚人群相比,历史上暴露于化学应激的水蚤人群表现出明显更大的健身影响。这项研究为PAHs与其他环境压力源相互作用的增强效应提供了重要见解。
    Polycyclic aromatic hydrocarbons (PAHs) arise from incomplete combustion of oil, coal, and gasoline, with lipophilic properties facilitating their widespread distribution and persistence. Due to their biochemical attributes, PAHs can accumulate in animal tissues, potentially causing mutagenic and carcinogenic effects. Since the industrial revolution, PAH concentrations in the environment have risen, with lakes showing levels from 0.159 to 33,090 μg/kg sediment. Despite acute toxicity studies showing adverse effects on freshwater organisms, the long-term impacts and synergistic interactions with other pollutants remain largely unexplored. This study investigates the impact of phenanthrene (PHE), a prominent PAH found in aquatic environments, on Daphnia magna, a species of significant ecological importance in freshwater ecosystems globally, being both a sentinel species for chemical pollution and a keystone organism in freshwater aquatic ecosystems. Leveraging the dormancy of D. magna, which spans decades or even centuries, we exposed strains with diverse histories of chemical contaminant exposure to environmentally relevant concentrations of PHE. Initially, acute exposure experiments were conducted in accordance with OECD guidelines across 16 Daphnia strains, revealing substantial variation in acute toxic responses, with strains naïve to chemical pollutants showing the lowest toxicity. Utilizing the median effect concentration EC10 derived from acute exposures, we assessed the impacts of chronic PHE exposure on life history traits and ecological endpoints of the 16 strains. To elucidate how historical exposure to other environmental stressors may modulate the toxicity of PHE, temporal populations of D. magna resurrected from a lake with a well-documented century-spanning history of environmental impact were utilized. Our findings demonstrate that PHE exposure induces developmental failure, delays sexual maturation, and reduces adult size in Daphnia. Populations of Daphnia historically exposed to chemical stress exhibited significantly greater fitness impacts compared to naïve populations. This study provides crucial insights into the augmented effects of PAHs interacting with other environmental stressors.
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  • 文章类型: Journal Article
    每年百万吨轮胎变成废物,将所谓的报废轮胎(ELTs)磨成粉末(ELT-dp;尺寸<0.8mm)和颗粒(ELT-dg;0.8<尺寸<2.5mm)用于回收。这项研究的目的是评估三种不同浓度(0.1、1和10mg/L)的ELT-dp和ELT-dg水性悬浮液对暴露于0至120h受精后(hpf)的Daniorerio(斑马鱼)幼虫的亚致死效应。通过生物标志物评估慢性效应,实时PCR,和蛋白质组学。我们观察到游泳行为和心率的显着增加,仅在暴露于1和10mg/L的ELT-dp悬浮液的标本中,分别。相反,解毒酶乙氧基间苯二酚-O-脱乙基酶(EROD)和谷胱甘肽-S-转移酶(GST)的活性仅在暴露于ELT-dg组的标本中显示出显着的调节。尽管通过实时PCR没有观察到影响,蛋白质组学强调了三种ELT-dp浓度在涉及芳香族化合物和氮化合物代谢途径的100多种蛋白质中引起的变化。获得的结果表明,ELT悬浮液的毒性作用机制(MoA)主要与水中释放的化学物质的诱导作用有关,与ELT-dg相比,ELT-dp的毒性更高。
    Million tons of tires become waste every year, and the so-called End-of-Life Tires (ELTs) are ground into powder (ELT-dp; size < 0.8 mm) and granules (ELT-dg; 0.8 < size < 2.5 mm) for recycling. The aim of this study was to evaluate the sub-lethal effects of three different concentrations (0.1, 1, and 10 mg/L) of aqueous suspensions from ELT-dp and ELT-dg on Danio rerio (zebrafish) larvae exposed from 0 to 120 h post-fertilization (hpf). Chronic effects were assessed through biomarkers, real-time PCR, and proteomics. We observed a significant increase in swimming behavior and heart rate only in specimens exposed to ELT-dp suspensions at 1 and 10 mg/L, respectively. Conversely, the activities of detoxifying enzymes ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST) showed significant modulation only in specimens exposed to ELT-dg groups. Although no effects were observed through real-time PCR, proteomics highlighted alterations induced by the three ELT-dp concentrations in over 100 proteins involved in metabolic pathways of aromatic and nitrogen compounds. The results obtained suggest that the toxic mechanism of action (MoA) of ELT suspensions is mainly associated with the induction of effects by released chemicals in water, with a higher toxicity of ELT-dp compared to ELT-dg.
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  • 文章类型: Journal Article
    Litseamartabanica(Kurz)Hook.f。由于泰国高地社区的保肝特性,传统上一直被用作抗杀虫剂和药物。这项研究检查了诱变性,以及急性和慢性毒性,在Sprague-Dawley大鼠中的马tabanica水叶提取物。在这项研究中进行了马氏乳杆菌的生药学评估,以确保其真实性和纯度。然后,用水煎剂提取样品,得到粗水提取物。急性毒性的评估涉及5000mg/kg的单次口服给药,而慢性毒性评估包括270天内每日口服剂量250,750和2250mg/kg.各种生理和行为参数,以及身体和器官的重量,系统监测。终点评估涉及血液学和生化分析以及内部器官的总体和组织病理学评估。我们的结果表明,在Ames试验中,马塔巴尼卡L.martabanica水叶提取物没有诱变活化,未观察到急性毒性。在慢性毒性试验中,在接受马氏乳杆菌水叶提取物的大鼠中,通过多种措施均未发现异常,包括行为,生理,和血液学指标。至关重要的是,组织病理学评估证实了以前的研究,报告没有任何组织异常。结果表明,口服给药270天对大鼠无不良影响。这证明了其安全性和重要的科学证据,可以为公共政策提供信息,并使其在高地和低地社区的潜在未来商业使用成为可能。
    Litsea martabanica (Kurz) Hook.f. has traditionally been used as an anti-insecticidal agent and as a medication due to its hepatoprotective properties by highland communities in Thailand. This study examined the mutagenicity, as well as the acute and chronic toxicity, of the L. martabanica water leaf extract in Sprague-Dawley rats. The pharmacognostic evaluation of L. martabanica was performed in this study to ensure its authenticity and purity. Then, the sample was extracted using decoction with water to obtain the crude water extract. The assessment of acute toxicity involved a single oral administration of 5000 mg/kg, whereas the chronic toxicity assessment comprised daily oral doses of 250, 750, and 2250 mg/kg over 270 days. Various physiological and behavioral parameters, as well as body and organ weights, were systematically monitored. The endpoint assessments involved hematological and biochemical analyses plus gross and histopathological assessments of the internal organs. Our results exhibited no mutagenic activation by the L. martabanica water leaf extract in the Ames test, and no acute toxicity was observed. In the chronic toxicity tests, no abnormalities were found in rats receiving the L. martabanica water leaf extract across multiple measures, comprising behavioral, physiological, and hematological indices. Crucially, the histopathological assessment corroborated previous studies, reporting an absence of any tissue abnormalities. The results revealed that the L. martabanica water leaf extract had no adverse effects on rats over 270 days of oral administration. This demonstrates its safety and crucial scientific evidence for informing public policy and enabling its potential future commercial use in both highland and lowland communities.
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  • 文章类型: Journal Article
    在生物学研究中对旋转磁场(RMF)的兴趣日益浓厚的背景下,关于RMF长期安全性的科学证据仍然存在显著差距。因此,这项研究旨在调查长期暴露于0.2T的安全性,在小鼠中经过10个月的4HzRMF。将两个月大的雌性C57BL/6小鼠随机分配到RMF组(暴露于0.2T,4Hz真实RMF)或SHAM组(暴露于0T,4Hz假RMF)。在整个实验过程中,记录了小鼠每周的体重,他们的行为特征是通过野外试验进行评估的。在最后一个月,对小鼠的整体健康状况进行了全面评估,包括血液参数的分析,主要器官的组织形态学检查,使用X射线和显微CT成像进行骨骼评估。通过免疫芯片分析和代谢组学评估小鼠免疫系统和脂质代谢。值得注意的是,没有观察到RMF暴露的明显不良反应.鼠体重,运动行为,器官组织形态学,骨骼健康不受RMF影响。血液分析显示,SHAM和RMF组之间的激素和脂质水平发生了细微变化,然而这些差异没有达到统计学意义.此外,RMF导致血清白细胞介素-28(IL-28)水平升高,尽管在正常范围内,和血清脂质代谢物的适度变化。最后,暴露于0.2T的小鼠,4HzRMF持续10个月没有显示出明显的慢性毒性迹象,表明其作为物理治疗的潜在临床应用。
    Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.
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  • 文章类型: Journal Article
    抗生素耐药性是与人类和动物之间的细菌和基因传播有关的全球健康问题。开发具有抗菌活性的新药是现代科学的紧迫任务。
    本文提供了基于乳酸链球菌素的新药物组合物的体外和体内实验数据。
    对乳腺炎病原体的抗菌活性进行了研究。为了鉴定微生物,使用基质辅助Lazer解吸/电离飞行时间(MALDI-TOF)(质谱)方法进行。为了确定灵敏度,采用连续稀释法和扩散法。关于实验动物,生物化学,血液学,采用组织学研究方法。使用雌性非线性白色实验室大鼠,分为一个对照组和三个实验组。
    \“持续时间\”因素对以下指标具有统计学意义:血红蛋白,血细胞比容,白细胞,淋巴细胞,红细胞沉降率,和嗜酸性粒细胞.“剂量”因子对任何指标都没有显着性,这意味着无论选择的剂量如何,效果都是相似的。在分析生化指标时,在“持续时间”和“剂量”因素上发现了显著差异,在总蛋白质指标下降的方向上,球蛋白,尿素,碱性磷酸酶的浓度增加。在第一个实验组进行组织学研究时,确定各机构的结构和职能单位没有变化。在第二实验组的动物中,注意到存在补偿性的可逆病理过程。在第三实验组中记录了所研究器官结构的更深刻变化。
    对细胞培养物的体外研究表明,该药理组合物对来自乳腺炎奶牛乳腺分泌物的分离物具有很高的抗菌活性。对实验动物的体内研究表明,开发的组合物属于IV类物质“低危害物质”。组织学检查可以选择不超过500mg/kg的药物组合物的最安全剂量。
    UNASSIGNED: Antibiotic resistance is a global health problem related to the transmission of bacteria and genes between humans and animals. The development of new drugs with antimicrobial activity research is an urgent task of modern science.
    UNASSIGNED: The article presents data of in vitro and in vivo experiments on new pharmaceutical composition based on nisin.
    UNASSIGNED: The antimicrobial activity was studied on the mastitis pathogens. To identify microorganisms the Matrix-Assisted Lazer Desorption/Ionization Time-of-Flight (MALDI-TOF) (mass spectrometry) method was performed using. To determine sensitivity, the serial dilution method and the diffusion method were used. On laboratory animals, biochemical, hematological, and histological research methods were used. Female nonlinear white laboratory rats were used, which were divided into one control group and three experimental ones.
    UNASSIGNED: \"Duration\" factor was statistically significant for the following indicators: hemoglobin, hematocrit, leukocytes, lymphocytes, erythrocyte sedimentation rate, and eosinophils. The \"Dose\" factor did not show significance for any indicator, which means that the effect was similar regardless of the dose chosen. When analyzing the biochemical indicators, significant differences were found in the \"Duration\" and \"Dose\" factors, in the direction of a decrease in the indicators of total protein, globulins, urea, and an increase in the concentration of alkaline phosphatase. When conducting histological studies in the first experimental group, it was established that there were no changes in the structural and functional units of the organs. In animals of the second experimental group, the presence of reversible pathological processes of a compensatory nature was noted. More profound changes in the structure of the studied organs were recorded in the third experimental group.
    UNASSIGNED: An in vitro study on cell cultures showed that the pharmacological composition has high antimicrobial activity against isolates from the mammary gland secretion of cows with mastitis. An in vivo study on laboratory animals showed that the developed composition belongs to the IV class of substances \"low-hazard substances\". Histological examination made it possible to select the safest dose of the pharmacological composition of no more than 500 mg/kg.
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  • 文章类型: Journal Article
    建立水蚤药物慢性毒性预测方法,我们研究了在大型蚤中结合药物靶向直系同源物的可行性,根据药理作用进行分类,生态毒性定量构效关系(QSAR)预测。我们建立了药物在水蚤中的慢性毒性的数据集,包括治疗类别的信息,靶蛋白,以及D.magna中是否存在药物靶向直系同源物,使用文献和数据库。使用生态毒性预测QSAR(生态结构活动关系和Kashhou生态毒性工具)预测慢性毒性,并检查了预测值和测量值之间的差异以及是否存在药物靶标直向同源物。对于在D.magna中没有药物靶向直系同源物或没有预期的特定行动的药物,生态毒性预测QSAR分析对药物的慢性毒性产生了可接受的预测。此外,在这些评价的基础上,我们提出了一个评估药物在水蚤中的慢性毒性的工作流程模型,并使用一个额外的数据集进行了验证.添加生物学方面,例如药物靶向直向同源物和药理作用,将支持使用QSAR预测药物在水蚤中的慢性毒性。
    To develop a method for predicting chronic toxicity of pharmaceuticals in Daphnia, we investigated the feasibility of combining the presence of drug-target orthologs in Daphnia magna, classification based on pharmacological effects, and ecotoxicity quantitative structure-activity relationship (QSAR) prediction. We established datasets on the chronic toxicity of pharmaceuticals in Daphnia, including information on therapeutic categories, target proteins, and the presence or absence of drug-target orthologs in D. magna, using literature and databases. Chronic toxicity was predicted using ecotoxicity prediction QSAR (Ecological Structure Activity Relationship and Kashinhou Tool for Ecotoxicity), and the differences between the predicted and measured values and the presence or absence of drug-target orthologs were examined. For pharmaceuticals without drug-target orthologs in D. magna or without expected specific actions, the ecotoxicity prediction QSAR analysis yielded acceptable predictions of the chronic toxicity of pharmaceuticals. In addition, a workflow model to assess the chronic toxicity of pharmaceuticals in Daphnia was proposed based on these evaluations and verified using an additional dataset. The addition of biological aspects such as drug-target orthologs and pharmacological effects would support the use of QSARs for predicting the chronic toxicity of pharmaceuticals in Daphnia.
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