Toxicology

毒理学
  • 文章类型: Journal Article
    婴儿双歧杆菌YLGB-1496,最初从台湾母亲的母乳中分离出来,正在研究用作益生菌。作为安全评估的一部分,一个艾姆斯,体内小鼠微核,并进行了为期13周的口服大鼠毒性研究,并进行了体内小鼠精母细胞染色体畸变测定。婴儿芽孢杆菌YLGB-1496在任何遗传毒性测定中都没有活性。以0至1.5g/kgbw/天的剂量向Sprague-Dawley大鼠施用细菌对所测量的任何终点都没有治疗相关的影响。基于对一般物种的广泛经验,似乎不担心婴儿双歧杆菌YLGB-1496的易位或致病性。当前研究的结果支持婴儿芽孢杆菌YLGB-1496作为婴儿配方中的益生菌的潜在用途。
    Bifidobacterium infantis YLGB-1496, originally isolated from breast milk from a Taiwanese mother, is under study for use as a probiotic. As part of safety assessment, an Ames, in vivo mouse micronucleus, and in vivo mouse spermatocyte chromosome aberration assay were conducted along with a 13-week oral rat toxicity study. B. infantis YLGB-1496 had no activity in any of the genotoxicity assays. Administration of the bacteria to Sprague-Dawley rats at doses ranging from 0 to 1.5 g/kg bw/day had no treatment-related effects on any of the endpoints measured. There appear to be no concerns for translocation or pathogenicity of B. infantis YLGB-1496 based on extensive experience with the species in general. The results of the current investigations support potential use of B. infantis YLGB-1496 as a probiotic in infant formula.
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  • 文章类型: Journal Article
    除草剂暴露给爬行动物带来更高的风险,因为它们经常与土壤接触。此外,食物限制也是一种常见的环境压力,会严重影响爬行动物的生存。面对新出现的除草剂污染和粮食短缺挑战,爬行动物的适应性策略尚不清楚。因此,选择EremiasArgus(一种小型爬行动物)作为模型来模拟蜥蜴食物短缺的真实场景,旨在探讨草铵膦(GLA:一种新兴的除草剂)和食物限制对蜥蜴的综合影响。结果表明,蜥蜴常通过体热选择来调节其生理生化活动,并倾向于选择较低的体温,降低消化率,并积极参与脂肪能量动员,避免饥饿状态下的氧化损伤,最后为了达到稳态。然而,除草剂GLA扰乱了蜥蜴抵抗食物短缺压力的努力,并干扰了面临饥饿的蜥蜴的正常体温调节和能量动员策略。这项研究的结果将提高我们对蜥蜴在极端压力下的影响的理解,有助于补充爬行动物毒理学数据,为除草剂GLA的风险评估提供科学依据。
    Herbicide exposure poses a higher risk to reptiles due to their frequent contact with soil. Besides, food restriction is also a common environmental pressure that can seriously affect the survival of reptiles. The adaptive strategies of reptiles in the face of emerging herbicide pollution and food shortage challenges are not yet known. Therefore, Eremias Argus (a kind of small reptile) was selected as the model to simulate the real scenario of food shortage in lizards, aiming to explore the comprehensive impact of glufosinate-ammonium (GLA: an emerging herbicide) and food restriction on lizards. The results revealed that lizards often regulate their physiological and biochemical activities through body thermal selection and tend to choose lower body temperature, reduce digestibility, and actively participate in fat energy mobilization to avoid oxidative damage in the state of hunger, finally in order to achieve homeostasis. However, herbicide GLA disrupted the lizards\' efforts to resist the stress of food shortage and interfered with the normal thermoregulation and energy mobilization strategies of lizards facing starvation. The results of this study would improve our understanding of the impacts of Lizards under extreme stresses, help supplement reptile toxicology data and provide scientific basis for the risk assessment of herbicide GLA.
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  • 文章类型: Journal Article
    巨翅目幼虫是重要的生物指示物种和潜在的资源昆虫。进一步培养他们的经济作用,必须更详细地检查他们的生活环境。在这项研究中,我们分析了亚致死剂量的吡虫啉的生理和生化效应,一种广泛使用的新烟碱杀虫剂,在原虫黄体的幼虫上。用吡虫啉治疗后,P.xanthodes幼虫表现出明显的中毒症状,包括头部向腹面蜷缩。此外,接触后,乙酰胆碱酯酶的活性受到显着抑制。谷胱甘肽S-转移酶的活性最初持续增加,但在8天后表现出轻微下降。过氧化氢酶活性最初增加,然后在吡虫啉处理后下降;超氧化物歧化酶活性随时间波动,过氧化物酶活性连续增加。使用qRT-PCR评估HSP70s基因的表达水平。这些结果表明,黄原虫幼虫对吡虫啉暴露表现出毒性反应,表现为氧化应激,通过行为和生理指标观察。
    Megaloptera larvae are important bioindicator species and potential resource insects. To further cultivate their economic role, their living environment must be examined in more detail. In this study, we analyzed the physiological and biochemical effects of a sublethal dose of imidacloprid, a widely used neonicotinoid insecticide, on the larvae of Protohermes xanthodes. After treatment with imidacloprid, P. xanthodes larvae exhibited clear symptoms of poisoning, including the head curling up toward the ventral surface. Additionally, the activity of acetylcholinesterase was significantly inhibited following exposure. The activities of glutathione S-transferases initially continuously increased but showed a slight decrease after 8 days. Catalase activity initially increased and then decreased following imidacloprid treatment; superoxide dismutase activity fluctuated over time, and peroxidase activity continuously increased. The expression levels of HSP70s genes were evaluated using qRT-PCR. These results indicate that P. xanthodes larvae exhibit a toxic response to imidacloprid exposure, manifested as oxidative stress, as observed through behavioral and physiological indicators.
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  • 文章类型: Journal Article
    背景:山豆根(STR),山豆根的干燥根和根茎。,通常用于治疗扁桃体炎和咽炎,喉咙疼痛和喉咙阻塞,牙龈肿胀和疼痛,等。在中国或其他亚洲国家。STR通常用作中药制剂中的核心草药,如“鼻咽灵片”,“复方无印良品颗粒”和“肝延灵注射液”,等。综述目的:本综述旨在从植物学角度对STR进行全面分析,传统使用,植物化学,民族药理学,药理学,药代动力学,毒理学和解毒策略,为今后的研究提供合理的应用。
    方法:研究涉及的信息来自各种电子资源,包括中国国家知识基础设施(CNKI),SciFinder,谷歌学者,PubMed,WebofScience,和中国硕士和博士学位论文。
    结果:到现在为止,STR中总共鉴定出333种化学成分,包括85种生物碱,124类黄酮,24个三萜,27三萜皂苷,34有机酸,8多糖,等。STR及其主要活性成分具有心血管保护作用,抗肿瘤活性,抗炎活性,解热活性,镇痛活性,抗菌活性,抗真菌活性,抗病毒活性,和肝保护活性,等。然而,STR对肝脏的毒性作用,神经,心,和胃肠道也被观察到。为了减轻这些风险,STR在使用前需要衰减,最常见的解毒方法是加工和与其他药物联合使用。对STR在体内的药代动力学以及含有STR的传统和临床处方进行了梳理。尽管STR具有潜在的治疗益处,进一步的研究是必要的,以阐明其肝脏毒性,特别是在体内,探索体内代谢等方面,分布,和机制。
    结论:这篇综述强调了STR的治疗潜力,并强调了在考虑临床应用之前解决其毒性问题的迫切需要。需要进一步研究以全面调查STR的毒理学特性,特别强调它的肝毒性和神经毒性。这样的研究努力有可能标准化STR的合理应用以获得最佳治疗结果。
    BACKGROUND: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as \"Biyanling Tablets\", \"Fufang Muji Granules\" and \"Ganyanling Injections\", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research.
    METHODS: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations.
    RESULTS: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms.
    CONCLUSIONS: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.
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  • 文章类型: Journal Article
    背景:Conioselinumanthriscoides(H.Boissieu)Pimenov&Kljuykov,又称川芎。是多年生伞形科草本植物,其干燥的根茎通常称为川芎。川芎在中医中应用广泛,特别是心脑血管和妇科疾病。然而,这些研究是分散的,没有评论可以集中这些研究的结果。作者通过收集有关化学,药理学,和川芎的毒理学在过去20年中发表在各种出版物上。
    目的:本文旨在总结目前川芎的实验研究,探讨其作用机制。
    方法:WebofScience,PubMed,CBM,CNKI,Medline,Embase,Elsevier,Springer,Wiley在线图书馆,学者,搜索了其他数据库,收集了近百项实验研究来总结这篇综述。
    结论:川芎由精油组成,萜烯,生物碱,多糖,有机酸,神经酰胺,和脑苷脂。它具有促进血液循环的功能,祛瘀,抗菌,抗病毒,让头脑平静入睡。现在可用于治疗心脑血管和妇科疾病,神经退行性疾病,牛皮癣,直肠癌,骨质疏松,和骨关节炎。
    结论:在过去的20年里,大量研究数据证实川芎含有丰富的有效代谢产物,具有巨大的药用潜力,并有广泛的有效治疗方法。
    BACKGROUND: Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, also known as Ligusticum chuanxiong Hort. is a perennial Umbelliferae herb, whose dried rhizome commonly called Chuanxiong Rhizoma. Chuanxiong Rhizoma is widely used in TCM, especially for cardiocerebrovascular and gynecological diseases. However, these studies are scattered and there is no review that can centralize the results of these studies. The authors summarized this review by collecting research results on the chemical, pharmacological, and toxicological of Chuanxiong Rhizoma published in various publications over the past 20 years.
    OBJECTIVE: The purpose of this review is to summarize the current experimental studies on Chuanxiong Rhizoma and explore its mechanism of action.
    METHODS: Web of Science, PubMed, CBM, CNKI, Medline, Embase, Elsevier, Springer, Wiley Online Library, Scholar, and other databases were searched, and nearly one hundred experimental studies were collected to summarize this review.
    CONCLUSIONS: Chuanxiong Rhizoma is composed of essential oil, terpenes, alkaloids, polysaccharide, organic acids, ceramides, and cerebrosides. It has the functions of promoting blood circulation, removing blood stasis, antibacterial, antiviral, and calming the mind to sleep. Now it can be used to treat cardiocerebrovascular and gynecological diseases, neurodegenerative disease, psoriasis, rectal cancer, osteoporosis, and osteoarthritis.
    CONCLUSIONS: In the past 20 years, a large number of research data have confirmed that Chuanxiong Rhizoma contains rich effective metabolites, has huge medicinal potential, and has a wide range of effective treatments.
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  • 文章类型: Journal Article
    近年来,动脉粥样硬化性心血管疾病的患病率和死亡率不仅显示出不可忽视的持续上升,但也已成为一个紧迫的社会健康问题,需要紧急关注。虽然介入手术和药物治疗提供了显著的治疗效果,它们经常伴随着常见的副作用。栀子苷,从中药栀子中提取的活性成分,在管理心脏病方面显示出希望。这篇综述全面概述了栀子苷对动脉粥样硬化的潜在药理机制。栀子苷表现出一系列有益的作用,包括缓解炎症,抑制巨噬细胞泡沫细胞的发育,改善脂质代谢,预防血小板聚集和血栓形成。它还展示了线粒体保护,抗凋亡作用,和自噬的调节。此外,栀子苷通过维持机体的抗氧化和氧化平衡,具有改善氧化应激和内质网应激的潜能。此外,这篇综述全面详细介绍了栀子苷的生物学特性,包括提取和纯化的方法,以及其药代动力学和毒理学特征。它进一步讨论了相关生物制药的临床应用,强调栀子苷在预防和治疗动脉粥样硬化性心血管疾病中的潜力。此外,它突出了当前研究的局限性,旨在为未来的研究提供见解。
    In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body\'s antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies.
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  • 文章类型: Journal Article
    背景:由于大量合成农药被广泛和不合理地用于作物保护,目前,对人类健康和环境安全的抗性和负面影响已经出现。因此,开发潜在的候选农药是非常紧迫的。在这里,设计并合成了一系列蛇床子素的酯衍生物作为杀虫剂。
    结果:4'-(对甲苯酰氧基)蛇床子素(4b)的六个空间构型,4'-(间氟苯甲酰基氧基)蛇床子素(4f),4'-(对氟苯基乙酰氧基)蛇床子素(4m),4\'-(3\'\',4\'\'-亚甲二氧基苯甲酰氧基)蛇床子素(4q),通过X射线单晶衍射测定了4'-甲酰基氧基蛇床子素(4u)和4'-乙酰氧基蛇床子素(4v)。化合物4b,4'-(对氯苯甲酰氧基)蛇床子素(4g),4'-(间氯苯甲酰氧基)蛇床子素(4h),4\'-(对溴苯甲酰氧基)蛇床子素(4i)和4\'-(2\''-氯吡啶-3\'''-羰基氧基)蛇床子素(4p)对MythimnaseparataWalker的杀虫活性高于秋葵素;特别是,化合物4b显示的杀虫活性是前体蛇床子素的1.8倍。对朱砂叶猴Boisduval,化合物4g和4h显示蛇床子素的3.3和2.6倍的杀螨活性,和良好的控制效果在温室。扫描电镜分析表明,化合物4g可以破坏朱砂角质层,导致死亡。
    结论:化合物4g和4h可以进一步研究作为铅杀虫剂用于分离M.separata和Cinnabarinus的管理。这些结果将为蛇床子素衍生物作为农用化学品的应用铺平道路。©2024化学工业学会。
    BACKGROUND: Owing to large amounts of synthetic pesticides being extensively and unreasonably used for crop protection, currently, resistance and negative impacts on human health and environment safety have appeared. Therefore, development of potential pesticide candidates is highly urgent. Herein, a series of ester derivatives of osthole were designed and synthesized as pesticidal agents.
    RESULTS: Six spatial configurations of 4\'-(p-toluenoyloxy)osthole (4b), 4\'-(m-fluorobenzoyloxy)osthole (4f), 4\'-(p-fluorophenylacetyloxy)osthole (4m), 4\'-(3\'\',4\'\'-methylenedioxybenzoyloxy)osthole (4q), 4\'-formyloxyosthole (4u) and 4\'-acetyloxyosthole (4v) were determined by X-ray mono-crystal diffraction. Compounds 4b, 4\'-(p-chlorobenzoyloxy)osthole (4g), 4\'-(m-chlorobenzoyloxy)osthole (4h), 4\'-(p-bromobenzoyloxy)osthole (4i) and 4\'-(2\'\'-chloropyridin-3\'\'-ylcarbonyloxy)osthole (4p) showed higher insecticidal activity than toosendanin against Mythimna separata Walker; notably, compound 4b displayed 1.8 times insecticidal activity of the precursor osthole. Against Tetranychus cinnabarinus Boisduval, compounds 4g and 4h showed 3.3 and 2.6 times acaricidal activity of osthole, and good control effects in the glasshouse. Scanning electron microscopy assay demonstrated that compound 4g can damage the cuticle layer of T. cinnabarinus resulting in death.
    CONCLUSIONS: Compounds 4g and 4h can be further studied as lead pesticidal agents for the management of M. separata and T. cinnabarinus. These results will pave the way for application of osthole derivatives as agrochemicals. © 2024 Society of Chemical Industry.
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  • 文章类型: Journal Article
    干细胞,具有自我更新和分化成各种细胞类型的能力,是医学研究和毒理学研究的独特而宝贵的资源。肝脏是人体最重要的代谢器官,并作为环境污染物积累的主要场所。环境污染物的富集会破坏肝脏的早期发育过程,并对肝功能产生重大影响。肝脏包含一系列复杂的细胞类型,不同的环境污染物对这些细胞有不同的影响。目前,目前还缺乏能够有效证明环境污染物影响人类肝脏发育机制的研究模型.肝细胞和源自干细胞的类器官的出现为研究环境污染物对人类健康的影响提供了有希望的工具。因此,本研究系统综述了不同类型肝细胞的发育过程,并对利用干细胞模型研究各种环境污染物的发育毒性进行了综述。
    Stem cells, with their ability to self-renew and differentiate into various cell types, are a unique and valuable resource for medical research and toxicological studies. The liver is the most crucial metabolic organ in the human body and serves as the primary site for the accumulation of environmental pollutants. Enrichment with environmental pollutants can disrupt the early developmental processes of the liver and have a significant impact on liver function. The liver comprises a complex array of cell types, and different environmental pollutants have varying effects on these cells. Currently, there is a lack of well-established research models that can effectively demonstrate the mechanisms by which environmental pollutants affect human liver development. The emergence of liver cells and organoids derived from stem cells offers a promising tool for investigating the impact of environmental pollutants on human health. Therefore, this study systematically reviewed the developmental processes of different types of liver cells and provided an overview of studies on the developmental toxicity of various environmental pollutants using stem cell models.
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  • 文章类型: Journal Article
    益母草是益母草属特有的生物碱,具有许多生物活性,如子宫收缩,抗炎,抗氧化,细胞凋亡的调节,抗肿瘤,血管生成,抗血小板聚集,和抑制血管收缩。本文总结了提取方法,合成途径,生物合成机制,药代动力学特性,在各种疾病的药理作用,毒理学,和益母草的临床试验。为了促进成功过渡到临床应用,需要在几个关键领域加大力度:益母草的结构修饰以优化其性能,全面的药代动力学评估,以了解其在体内的行为,彻底的机械研究,以阐明它是如何在分子水平上工作的,严格的安全评估和毒理学调查,以确保患者的健康,并精心进行临床试验,以验证其疗效和安全性。
    Leonurine is an alkaloid unique to the Leonurus genus, which has many biological activities, such as uterine contraction, anti-inflammation, anti-oxidation, regulation of cell apoptosis, anti-tumor, angiogenesis, anti-platelet aggregation, and inhibition of vasoconstriction. This paper summarizes the extraction methods, synthetic pathways, biosynthetic mechanisms, pharmacokinetic properties, pharmacological effects in various diseases, toxicology, and clinical trials of leonurine. To facilitate a successful transition into clinical application, intensified efforts are required in several key areas: structural modifications of leonurine to optimize its properties, comprehensive pharmacokinetic assessments to understand its behavior within the body, thorough mechanistic studies to elucidate how it works at the molecular level, rigorous safety evaluations and toxicological investigations to ensure patient wellbeing, and meticulously conducted clinical trials to validate its efficacy and safety profile.
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  • 文章类型: Journal Article
    化合物和厚朴酚,来源于厚朴的树皮,具有诱导细胞凋亡和抑制活性氧引起的细胞损伤的能力。这项研究的目的是通过进行半静态急性毒性试验,研究和厚朴酚对斑马鱼(Daniorerio)的毒理学和组织病理学影响,该试验涉及浸入含和厚朴酚的溶液中。结果表明,和厚朴酚对斑马鱼的毒性作用主要表现在肝脏和ill。当暴露于0.6毫克/升的和厚朴酚时,它可能导致肝脏出血以及ill组织肿胀和坏死,高浓度和厚朴酚可引发炎症反应。此外,研究发现,和厚朴酚可通过P53途径诱导肝脏和ill组织凋亡,并具有增强抗氧化能力。本研究的发现大大有助于更深刻地理解和厚朴酚的毒性影响及其潜在的机制,从而为今后和厚朴酚的安全利用及相关药物进展提供有价值的参考。
    The compound Honokiol, derived from the bark of Magnolia officinalis, possesses the ability to induce apoptosis and inhibit cellular damage caused by reactive oxygen species. The objective of this study was to investigate the toxicological and histopathological effects of Honokiol on zebrafish (Danio rerio) through conducting a semistatic acute toxicity test involving immersion in an Honokiol-containing solution. The results showed that the toxic effects of Honokiol on zebrafish were primarily manifested in the liver and gills. When exposed to 0.6 mg/L of Honokiol, it could lead to liver hemorrhage as well as swelling and necrosis of gill tissues, and high concentrations of Honokiol could trigger inflammatory responses. Additionally, research found that Honokiol could induce apoptosis in liver and gill tissues through the P53 pathway and possessed the ability to enhance antioxidation. The present findings significantly contribute to a more profound understanding of the toxic impact of Honokiol and its underlying mechanism, thereby providing a valuable reference for the future safe utilization of Honokiol and related pharmaceutical advancements.
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