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Sublethal Effects of Cadmium on the Osmoregulatory and Acid-Base Parameters of Tilapia (Oreochromis niloticus) at Various Times. 不同时期镉对罗非鱼渗透调节和酸碱参数的亚致死效应。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1155/2023/2857650
Agoes Soegianto, Bambang Yulianto, Carolyn Melissa Payus, Moch Affandi, Wildanun Mukholladun, Khudrotul Nisa Indriyasari, Ary Marchellina, Nailul Muthiati Rahmatin

Background: Cadmium (Cd) can contaminate aquatic environments as a result of anthropogenic activity. Cd accumulates quickly in the tissues of fish and has the potential to affect their physiology, including osmoregulation and acid-base balance. Therefore, the purpose of this study was to examine the sublethal effects of Cd on the osmoregulation and acid-base balance of tilapia Oreochromis niloticus at different times.

Methods: Fish were exposed to sublethal concentrations of Cd (1 and 2 mg/L) for 4 and 15 days. At the end of the experiment, fish were collected from each treatment to examine the levels of Cd and carbonic anhydrase (CA) in the gills, plasma osmolality, ions, blood pH, pCO2, pO2, and hematological parameters.

Results: Cd concentrations in gills rose with increasing Cd concentrations in the medium and exposure time. Cd inhibited respiration by generating metabolic acidosis, decreasing gill CA, reducing pO2, plasma osmolality, Cl-, and K+, particularly at 2 mg/L for 4 days and 1 and 2 mg/L for 15 days. Red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels decreased as Cd levels in water and exposure duration increased.

Conclusion: Cd inhibits respiration, lowers RCB, Hb, and Ht levels and decreases ionic and osmotic regulation. All of these impairments can limit a fish's ability to provide appropriate oxygen to its cells, hence diminishing its physical activity and productivity.

背景:镉(Cd)可以污染水生环境的人为活动的结果。镉在鱼的组织中迅速积累,并有可能影响鱼的生理机能,包括渗透调节和酸碱平衡。因此,本研究的目的是研究不同时期镉对尼罗罗非鱼渗透调节和酸碱平衡的亚致死效应。方法:将鱼暴露于亚致死浓度的Cd(1和2 mg/L)中4天和15天。在试验结束时,收集每个处理的鱼,检测鱼鳃中Cd和碳酸酐酶(CA)水平、血浆渗透压、离子、血液pH、pCO2、pO2和血液学参数。结果:鱼鳃中Cd浓度随培养基中Cd浓度和暴露时间的增加而升高。Cd通过产生代谢性酸中毒、降低鳃CA、降低pO2、血浆渗透压、Cl-和K+来抑制呼吸,特别是在2 mg/L持续4天、1和2 mg/L持续15天的情况下。红细胞(RBC)、血红蛋白(Hb)和红细胞压积(Ht)水平随着水中镉含量和暴露时间的增加而降低。结论:Cd抑制呼吸,降低RCB、Hb和Ht水平,降低离子和渗透调节。所有这些损伤都会限制鱼类向细胞提供适当氧气的能力,从而减少其身体活动和生产力。
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引用次数: 1
Acute and Repeated Dose 28-Day Oral Toxicity Study of the Aqueous Extracts from the Leafy Stem and Fruit of Pedalium murex D.Royen EX.L in Wistar Rats. 紫檀叶茎和果实水提物对Wistar大鼠急性和重复剂量28天口服毒性研究。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2023-01-01 DOI: 10.1155/2023/2962905
Gérard Bessan Dossou-Agoin, Maxime Machioud Sangaré-Oumar, Téniola Isabelle Sacramento, Mariette Sindété, Egnon Jacques Hougbénou-Houngla, Nounagnon Darius Tossavi, Simon Azonbakin, Adam Gbankoto

Background: Pedalium murex (P. murex) is used in folk medicine for treatment of male infertility. However, scientific data on its safety are limited.

Objective: This study was carried out to assess the acute and repeated dose 28-day oral toxicity of the aqueous extracts from P. murex leafy stem and fruit in Wistar rats.

Methods: The acute toxicity test was performed according to the line 423 of the Organization for Economic Cooperation and Development (OECD) guidelines. The rats were randomly divided into three groups (n = 3). The control group received distilled water, while the experimental groups were given at a single dose, 5000 mg/kg of each extract. The repeated dose 28-day oral toxicity was performed according to the line 407 of the OECD guidelines. 35 rats divided into 7 groups of 5 male rats each were daily treated for 28 days with each extract at 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The in-life parameters were recorded during the follow-up. At the end of this study, organ weights, hematology, biochemistry, and histology parameters were analyzed.

Results: In the acute oral toxicity test, there was no morbidity or mortality related to the treatments. Both extracts belong therefore to category 5 of the globally harmonized system (GHS) of classification. In the repeated dose 28-day oral toxicity test, both extracts did not alter animal's behavior. However, both extract administration led to proteinuria and renal damages.

Conclusion: P. murex leafy stem and fruit aqueous extracts exhibited potential nephrotoxicity. Therefore, care should be taken when they are used over an extended period.

背景:黄脚草在民间医学中用于治疗男性不育症。然而,关于其安全性的科学数据是有限的。目的:本研究以Wistar大鼠为研究对象,观察其叶茎和果实水提物的急性和重复剂量28 d口服毒性。方法:按照经济合作与发展组织(OECD)指南第423行进行急性毒性试验。将大鼠随机分为3组(n = 3)。对照组给予蒸馏水,试验组给予单剂量,每次提取物5000 mg/kg。重复剂量28天口服毒性试验按照OECD指南第407行进行。35只大鼠分为7组,每组5只雄性大鼠,每天分别给予200、400、800 mg/kg的剂量,连续治疗28 d。在随访期间记录生活参数。在研究结束时,对器官重量、血液学、生物化学和组织学参数进行分析。结果:在急性口服毒性试验中,无与治疗相关的发病率和死亡率。因此,这两种提取物都属于全球统一分类制度(GHS)的第5类。在重复给药28天的口服毒性试验中,两种提取物均未改变动物的行为。然而,两种提取物均导致蛋白尿和肾脏损害。结论:野鼠叶茎和果实水提物具有潜在的肾毒性。因此,在长时间使用时应多加小心。
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引用次数: 1
Toxicological Assessments of a Proprietary Blend of Punica granatum Fruit Rind and Theobroma cacao Seed Extracts: Acute, Subchronic, and Genetic Toxicity Studies 石榴果皮和可可籽提取物专有混合物的毒理学评估:急性、亚慢性和遗传毒性研究
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-05-06 DOI: 10.1155/2022/3903943
Ravi Kumar Madireddy, K. V. Alluri, Venkateswarlu Somepalli, T. Golakoti, K. Sengupta
LN18178 (Tesnor®) is a standardized, proprietary composition of aqueous ethanol extracts of Punica granatum fruit rind and Theobroma cacao seeds. The present study demonstrates a broad-spectrum toxicological evaluation of LN18178 utilizing in vitro and in vivo preclinical models following the Organization for Economic Cooperation and Development (OECD) guidelines for testing chemicals. Wistar rats did not show any clinical signs of toxicity and morbidity in acute oral and dermal toxicity tests with the median lethal dose (LD50) values of at least 5000 mg/kg and 2000 mg/kg body weight, respectively. LN18178 was nonirritating to the skin and eyes of the treated rabbits. In a ninety-day subchronic repeated oral dose toxicity study, the LN18178-treated Wistar rats did not show dose-related signs of toxicity on their body weight, food consumption, organ weights, hematology, and clinical chemistry parameters. The estimated no-observed-adverse-effect level (NOAEL) of LN18178 in male and female rats was 2500 mg/kg body weight. The observations from the bacterial reverse mutation test, in vitro chromosomal aberration assay, micronucleus assay in mouse bone marrow erythrocytes, and in vitro mouse lymphoma TK+/− gene mutation assay suggest that LN18178 is neither mutagenic nor clastogenic. In summary, the present study demonstrates that oral consumption of the herbal blend LN18178 does not show signs of toxicity; also it does not elicit genetic toxicity in the standard preclinical models.
LN18178 (Tesnor®)是一种标准化的专利组合物,由石榴果皮和可可种子的水乙醇提取物组成。本研究根据经济合作与发展组织(OECD)化学品测试指南,利用体外和体内临床前模型对LN18178进行了广谱毒理学评估。在急性口服和皮肤毒性试验中,Wistar大鼠的中位致死剂量(LD50)分别至少为5000 mg/kg和2000 mg/kg体重,未显示出任何毒性和发病的临床迹象。LN18178对治疗兔的皮肤和眼睛无刺激性。在一项为期90天的亚慢性重复口服剂量毒性研究中,ln18178治疗的Wistar大鼠在体重、食物消耗、器官重量、血液学和临床化学参数方面没有显示出剂量相关的毒性迹象。LN18178在雄性和雌性大鼠中估计的无观察到不良反应水平(NOAEL)为2500 mg/kg体重。细菌反向突变试验、体外染色体畸变试验、小鼠骨髓红细胞微核试验和小鼠淋巴瘤TK+/ -基因体外突变试验表明,LN18178不具有致突变性和致裂性。总之,目前的研究表明,口服混合草药LN18178没有毒性迹象;在标准的临床前模型中,它也不会引起遗传毒性。
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引用次数: 4
Iron Chelators in Treatment of Iron Overload 铁螯合剂处理铁超载
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-05-05 DOI: 10.1155/2022/4911205
Sarina Entezari, Seyedeh Mona Haghi, Narges Norouzkhani, Barsa Sahebnazar, Fatemeh Vosoughian, Diba Akbarzadeh, Muhammad Islampanah, Navid Naghsh, Mohammad Abbasalizadeh, N. Deravi
Patients suffering from iron overload can experience serious complications. In such patients, various organs, such as endocrine glands and liver, can be damaged. Although iron is a crucial element for life, iron overload can be potentially toxic for human cells due to its role in generating free radicals. In the past few decades, there has been a major improvement in the survival of patients who suffer from iron overload due to the application of iron chelation therapy in clinical practice. In clinical use, deferoxamine, deferiprone, and deferasirox are the three United States Food and Drug Administration-approved iron chelators. Each of these iron chelators is well known for the treatment of iron overload in various clinical conditions. Based on several up-to-date studies, this study explained iron overload and its clinical symptoms, introduced each of the above-mentioned iron chelators, and evaluated their advantages and disadvantages with an emphasis on combination therapy, which in recent studies seems a promising approach. In numerous clinical conditions, due to the lack of accurate indicators, choosing a standard approach for iron chelation therapy can be difficult; therefore, further studies on the issue are still required. This study aimed to introduce each of these iron chelators, combination therapy, usage doses, specific clinical applications, and their advantages, toxicity, and side effects.
患有铁过载的患者可能会出现严重的并发症。这类患者的各种器官,如内分泌腺和肝脏,都可能受到损害。尽管铁是生命的关键元素,但由于铁在产生自由基方面的作用,铁过载可能对人体细胞具有潜在毒性。在过去的几十年里,由于在临床实践中应用了铁螯合疗法,铁超负荷患者的生存率有了重大提高。在临床应用中,去铁胺、去铁酮和去铁罗克斯是美国食品和药物管理局批准的三种铁螯合剂。这些铁螯合剂中的每一种都是众所周知的,用于治疗各种临床条件下的铁过载。基于几项最新研究,本研究解释了铁过载及其临床症状,介绍了上述每种铁螯合剂,并评估了它们的优缺点,重点是联合治疗,在最近的研究中,这似乎是一种很有前途的方法。在许多临床情况下,由于缺乏准确的指标,选择铁螯合治疗的标准方法可能很困难;因此,这一问题还有待进一步研究。本研究旨在介绍每种铁螯合剂、联合治疗、使用剂量、具体临床应用及其优点、毒性和副作用。
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引用次数: 21
Review of Cyanotoxicity Studies Based on Cell Cultures 基于细胞培养的氰毒性研究综述
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-04-25 DOI: 10.1155/2022/5647178
Iliyana Sazdova, M. Keremidarska-Markova, M. Chichova, Blagoy A. Uzunov, G. Nikolaev, M. Mladenov, R. Schubert, Maya P. Stoyneva-Gärtner, H. Gagov
Cyanotoxins (CTs) are a large and diverse group of toxins produced by the peculiar photosynthetic prokaryotes of the domain Cyanoprokaryota. Toxin-producing aquatic cyanoprokaryotes can develop in mass, causing “water blooms” or “cyanoblooms,” which may lead to environmental disaster—water poisoning, extinction of aquatic life, and even to human death. CT studies on single cells and cells in culture are an important stage of toxicological studies with increasing impact for their further use for scientific and clinical purposes, and for policies of environmental protection. The higher cost of animal use and continuous resistance to the use of animals for scientific and toxicological studies lead to a progressive increase of cell lines use. This review aims to present (1) the important results of the effects of CT on human and animal cell lines, (2) the methods and concentrations used to obtain these results, (3) the studied cell lines and their tissues of origin, and (4) the intracellular targets of CT. CTs reviewed are presented in alphabetical order as follows: aeruginosins, anatoxins, BMAA (β-N-methylamino-L-alanine), cylindrospermopsins, depsipeptides, lipopolysaccharides, lyngbyatoxins, microcystins, nodularins, cyanobacterial retinoids, and saxitoxins. The presence of all these data in a review allows in one look to advance the research on CT using cell cultures by facilitating the selection of the most appropriate methods, conditions, and cell lines for future toxicological, pharmacological, and physiological studies.
蓝藻毒素(CTs)是由蓝藻原核生物域中特殊的光合作用原核生物产生的一大类多样的毒素。产生毒素的水生蓝藻原核生物可以大量生长,造成“水华”或“蓝藻”,这可能导致环境灾难-水中毒,水生生物灭绝,甚至人类死亡。单细胞和培养细胞的CT研究是毒理学研究的一个重要阶段,对其进一步用于科学和临床目的以及环境保护政策的影响越来越大。较高的动物使用成本和对使用动物进行科学和毒理学研究的持续抵制导致细胞系使用的逐步增加。本文旨在介绍(1)CT对人类和动物细胞系影响的重要结果,(2)获得这些结果的方法和浓度,(3)所研究的细胞系及其来源组织,以及(4)CT的细胞内靶点。本文按字母顺序综述了以下ct:铜绿毒素,anatoxin, BMAA (β- n -甲氨基- l -丙氨酸),圆柱精子蛋白,沉积肽,脂多糖,lynbyatoxin,微囊藻毒素,结核毒素,蓝藻类维生素a,和蛤蚌毒素。在一篇综述中,所有这些数据的存在,可以通过促进选择最合适的方法、条件和细胞系,为未来的毒理学、药理学和生理学研究,一次性推进CT使用细胞培养的研究。
{"title":"Review of Cyanotoxicity Studies Based on Cell Cultures","authors":"Iliyana Sazdova, M. Keremidarska-Markova, M. Chichova, Blagoy A. Uzunov, G. Nikolaev, M. Mladenov, R. Schubert, Maya P. Stoyneva-Gärtner, H. Gagov","doi":"10.1155/2022/5647178","DOIUrl":"https://doi.org/10.1155/2022/5647178","url":null,"abstract":"Cyanotoxins (CTs) are a large and diverse group of toxins produced by the peculiar photosynthetic prokaryotes of the domain Cyanoprokaryota. Toxin-producing aquatic cyanoprokaryotes can develop in mass, causing “water blooms” or “cyanoblooms,” which may lead to environmental disaster—water poisoning, extinction of aquatic life, and even to human death. CT studies on single cells and cells in culture are an important stage of toxicological studies with increasing impact for their further use for scientific and clinical purposes, and for policies of environmental protection. The higher cost of animal use and continuous resistance to the use of animals for scientific and toxicological studies lead to a progressive increase of cell lines use. This review aims to present (1) the important results of the effects of CT on human and animal cell lines, (2) the methods and concentrations used to obtain these results, (3) the studied cell lines and their tissues of origin, and (4) the intracellular targets of CT. CTs reviewed are presented in alphabetical order as follows: aeruginosins, anatoxins, BMAA (β-N-methylamino-L-alanine), cylindrospermopsins, depsipeptides, lipopolysaccharides, lyngbyatoxins, microcystins, nodularins, cyanobacterial retinoids, and saxitoxins. The presence of all these data in a review allows in one look to advance the research on CT using cell cultures by facilitating the selection of the most appropriate methods, conditions, and cell lines for future toxicological, pharmacological, and physiological studies.","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2022 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64781962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Nephroprotective Effect of Asparagus africanus Lam. Root Extract against Gentamicin-Induced Nephrotoxicity in Swiss Albino Mice 芦笋的肾保护作用。根提取物对庆大霉素所致瑞士白化小鼠肾毒性的影响
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-04-21 DOI: 10.1155/2022/8440019
Welela Meka Kedir, Abebe Dukassa Dubiwak, Ebsa Tofik Ahmed
The kidney is the organ most vulnerable to nephrotoxic drugs such as gentamicin. Nephrotoxicity is a rapid deterioration of kidney function due to various factors. Gentamicin causes nephrotoxicity, which was manifested by an increase in serum kidney biomarkers. Asparagus africanus is one of the ethnomedicinal plants used as traditional medicine for treating various ailments, including kidney disease in Ethiopian society. Thus, the aim of this study is to evaluate the nephroprotective effect of A. africanus root extract on gentamicin-induced nephrotoxicity. Using maceration techniques, 100 g of dried plant powder was extracted in 1 L of ethanol. The physicochemical screening of plant extracts revealed the presence of flavonoids, phenols, tannins, saponins, and steroids. The nephroprotective activity of A. africanus crude extract was evaluated on male Swiss albino mice. The crude ethanolic extract at 200 and 400 mg/kg doses showed strong nephroprotective effects by restoring biomarkers such as creatinine, uric acid, and blood urea nitrogen, which were damaged by gentamicin (p < 0.05) in a dose-dependent manner. The mice treated with higher doses (400 mg/kg) had a comparable nephroprotective effect compared to the positive control group (200 mg/kg silymarin; p > 0.05). The histopathology of the control group showed normal glomeruli, normal parenchyma, distal convoluted, and no tubular damage. The toxicant-induced group showed damage to glomeruli and inflammatory infiltration. Therefore, A. africanus root extract has a nephroprotective activity by retarding the gentamicin toxicity in male Swiss albino mice.
肾脏是最容易受到肾毒性药物如庆大霉素影响的器官。肾毒性是由多种因素引起的肾功能迅速恶化。庆大霉素引起肾毒性,表现为血清肾生物标志物的增加。非洲芦笋是一种民族药用植物,在埃塞俄比亚社会被用作治疗各种疾病的传统药物,包括肾病。因此,本研究的目的是评估非洲根提取物对庆大霉素引起的肾毒性的肾保护作用。采用浸渍技术,用1 L乙醇提取100 g干燥植物粉。对植物提取物进行理化筛选,发现其含有黄酮类、酚类、单宁类、皂苷类和甾类化合物。研究了非洲麻粗提物对雄性瑞士白化小鼠的肾保护作用。在200和400 mg/kg剂量下,粗乙醇提取物可恢复庆大霉素损伤的生物标志物肌酐、尿酸和血尿素氮(p < 0.05),并呈剂量依赖性,显示出较强的肾保护作用。与阳性对照组(水飞蓟素200 mg/kg;P < 0.05)。对照组肾小球组织病理正常,实质正常,远曲,肾小管未见损伤。毒性诱导组出现肾小球损伤和炎症浸润。因此,非洲根提取物具有延缓庆大霉素对雄性瑞士白化小鼠肾保护作用。
{"title":"Nephroprotective Effect of Asparagus africanus Lam. Root Extract against Gentamicin-Induced Nephrotoxicity in Swiss Albino Mice","authors":"Welela Meka Kedir, Abebe Dukassa Dubiwak, Ebsa Tofik Ahmed","doi":"10.1155/2022/8440019","DOIUrl":"https://doi.org/10.1155/2022/8440019","url":null,"abstract":"The kidney is the organ most vulnerable to nephrotoxic drugs such as gentamicin. Nephrotoxicity is a rapid deterioration of kidney function due to various factors. Gentamicin causes nephrotoxicity, which was manifested by an increase in serum kidney biomarkers. Asparagus africanus is one of the ethnomedicinal plants used as traditional medicine for treating various ailments, including kidney disease in Ethiopian society. Thus, the aim of this study is to evaluate the nephroprotective effect of A. africanus root extract on gentamicin-induced nephrotoxicity. Using maceration techniques, 100 g of dried plant powder was extracted in 1 L of ethanol. The physicochemical screening of plant extracts revealed the presence of flavonoids, phenols, tannins, saponins, and steroids. The nephroprotective activity of A. africanus crude extract was evaluated on male Swiss albino mice. The crude ethanolic extract at 200 and 400 mg/kg doses showed strong nephroprotective effects by restoring biomarkers such as creatinine, uric acid, and blood urea nitrogen, which were damaged by gentamicin (p < 0.05) in a dose-dependent manner. The mice treated with higher doses (400 mg/kg) had a comparable nephroprotective effect compared to the positive control group (200 mg/kg silymarin; p > 0.05). The histopathology of the control group showed normal glomeruli, normal parenchyma, distal convoluted, and no tubular damage. The toxicant-induced group showed damage to glomeruli and inflammatory infiltration. Therefore, A. africanus root extract has a nephroprotective activity by retarding the gentamicin toxicity in male Swiss albino mice.","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2022 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41402190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
The Developmental Toxicity of Thymus schimperi Essential Oil in Rat Embryos and Fetuses 香胸腺精油对大鼠胚胎和胎儿的发育毒性研究
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-04-11 DOI: 10.1155/2022/4091839
Fentahun Adane, K. Asres, W. Ergete, Samuel Woldekidan, G. Seyoum
Background In Ethiopian traditional medicine, the aerial parts of Thymus schimperi are widely used to treat diseases such as gonorrhea, cough, liver disease, kidney disease, hypertension, stomach pain, and fungal skin infections. In addition, they have been used as vegetables to flavor a broad variety of food products. However, there is an insufficient investigation of the toxic effect of Thymus schimperi essential oil. The aim of this study was, therefore, to evaluate the developmental toxicity of the essential oil of Thymus schimperi leaves on developing rat embryos and fetuses. Methods Essential oil of the aerial parts of Thymus schimperi was extracted by hydrodistillation. Pregnant Wistar albino rats were randomly divided into five groups. The doses 65 mg/kg, 130 mg/kg, and 260 mg/kg of the essential of Thymus schimperi were administered by force feeding to the III–V groups, respectively. Groups I and II were negative and ad libitum control groups. The embryos and fetuses were revealed on days 12 and 20 of gestations, respectively. The embryos were examined for developmental delays or growth retardation. Gross external, skeletal, and visceral anomalies in the fetuses were examined. Results In this study, the developmental scores of the number of implantation sites, crown-rump length, the number of somites, and morphological scores were significantly lower while the score of fetal resorptions was increased in a 12-day-old rat embryos treated with 260 mg/kg of the Thymus schimperi essential oil. There was also a significant delay in the development of the otic system, olfactory system, and a reduction in the number of branchial bars in 12-day-old embryos treated with 130 mg/kg and 260 mg/kg of the essential oil. However, external morphological examinations of rat fetuses revealed no detectable structural abnormalities. The fetal skull, vertebrae, hyoid, forelimb, and hindlimb ossification centers did not differ significantly across all the groups. Furthermore, there were no skeletal or soft-tissue malformations as a result of the essential oil treatment. Although the difference was not statistically significant, fetuses of the high-dose treatment group had a reduced number of ossification centers in the caudal vertebrae and hind limp phalanges. Conclusion The essential oil of Thymus schimperi at high doses has a detrimental effect on the development of rat embryos and fetuses. Its developmental toxicity is evidenced by significant delays in fetal and embryonic development, a decrease in the number of implantation sites, and an increase in fetal resorption. Furthermore, administration of the essential oil in higher doses resulted in a significant decrease in placenta weight and litter weight. In addition, the present study provided evidence that using the Thymus schimperi essential oil in a high dose could affect the developing embryo and fetus. Thus, it is recommended to discourage the use of Thymus schimperi essential oil in high doses.
背景在埃塞俄比亚传统医学中,百里香的地上部分被广泛用于治疗淋病、咳嗽、肝病、肾病、高血压、胃痛和真菌性皮肤感染等疾病。此外,它们还被用作蔬菜,为各种各样的食品调味。然而,对千里挥发油的毒性作用研究不足。因此,本研究的目的是评估百里香叶精油对发育中的大鼠胚胎和胎儿的发育毒性。方法采用水蒸馏法提取山胸腺地上部分挥发油。将怀孕的Wistar白化大鼠随机分为五组。剂量65 mg/kg,130 mg/kg和260 III–V组分别通过强制喂食的方式给药mg/kg的百里香精油。第一组和第二组为阴性对照组和随意对照组。胚胎和胎儿分别在妊娠第12天和第20天出现。对胚胎进行发育迟缓或生长迟缓检查。检查胎儿的大体外部、骨骼和内脏异常。结果在本研究中,用260 毫克/千克的百里香精油。在用130处理的12天大的胚胎中,耳系统、嗅觉系统的发育也显著延迟,鳃条的数量也减少 mg/kg和260 mg/kg的精油。然而,大鼠胎儿的外部形态学检查没有发现可检测到的结构异常。胎儿颅骨、脊椎、舌骨、前肢和后肢骨化中心在所有组之间没有显著差异。此外,精油治疗后没有出现骨骼或软组织畸形。尽管差异没有统计学意义,但高剂量治疗组的胎儿尾椎骨和后跛行指骨的骨化中心数量减少。结论大剂量山百里香精油对大鼠胚胎和胎儿发育有不良影响。其发育毒性可通过胎儿和胚胎发育的显著延迟、植入部位数量的减少和胎儿吸收的增加来证明。此外,更高剂量的精油给药可显著降低胎盘重量和产仔重量。此外,本研究提供了证据,证明高剂量使用百里香精油会影响发育中的胚胎和胎儿。因此,建议不要大剂量使用百里香精油。
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引用次数: 4
Acute and Subchronic Toxicity Study of Flavonoid Rich Extract of Glycyrrhiza glabra (GutGard®) in Sprague Dawley Rats 甘草黄酮提取物对大鼠的急性和亚慢性毒性研究
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-03-31 DOI: 10.1155/2022/8517603
Ranjit M. Bhide, Bharathi Bethapudi, N. S. S. Chalichem, Muruganantham Nithyanantham, Sasikumar Murugan, Deepak Mundkinajeddu
Glycyrrhiza glabra (G. glabra) is well known for its health benefits based on the traditional and current scientific evidence. The aim of the present study was to evaluate the safety of GutGard, a standardised-flavonoid rich extract of G. glabra. The study was designed to evaluate the acute and subchronic oral toxicity of GutGard in Sprague Dawley rats according to the procedures and methods of Organisation for Economic Cooperation and Development (OECD) test guidelines for acute and subchronic toxicity. A single dose of GutGard at 5000 mg/kg body weight did not produce treatment related clinical signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the median lethal dose was estimated to be more than 5000 mg/kg. A subchronic oral toxicity study for 90 days in rats at the dose levels of 250, 500, and 1000 mg/kg did not show any treatment related adverse clinical signs. The treated animals exhibited normal weight gain and comparable feed intake. Ophthalmoscope examination did not reveal any abnormalities. Further, GutGard administration in rats did not show any clinical evidence of toxicity with respect to urinalysis, haematology, and blood chemistry parameters. The relative organ weight of vital organs did not differ significantly as compared to control. Gross and histopathological findings did not show any remarkable and treatment related changes. Based on the current experimental study findings, the median lethal dose (LD50) of GutGard was found to be >5000 mg/kg b.wt and the no observed adverse effect level (NOAEL) was found to be 1000 mg/kg rat b.wt.
甘草(G. glabra)是众所周知的健康益处基于传统和当前的科学证据。本研究的目的是评估GutGard的安全性,GutGard是一种标准的富含黄酮类化合物的提取物。本研究按照经济合作与发展组织(OECD)急性和亚慢性毒性试验指南的程序和方法,评价GutGard对Sprague Dawley大鼠的急性和亚慢性毒性。在14天的观察期内,单剂量5000mg /kg体重的GutGard未在任何试验动物中产生与治疗相关的毒性或死亡临床症状。因此,中位致死剂量估计超过5000mg /kg。对大鼠进行了为期90天的亚慢性口服毒性研究,剂量水平分别为250、500和1000 mg/kg,未显示出任何与治疗相关的不良临床症状。接受治疗的动物表现出正常的体重增加和相当的采食量。检眼镜检查未见异常。此外,大鼠GutGard给药在尿液分析、血液学和血液化学参数方面没有显示出任何毒性的临床证据。各重要脏器相对重量与对照组相比无显著差异。大体和组织病理学检查未见任何显著的与治疗相关的改变。根据目前的实验研究结果,发现GutGard的中位致死剂量(LD50)为50 ~ 5000 mg/kg b.wt,未观察到的不良反应水平(NOAEL)为1000 mg/kg大鼠b.wt。
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引用次数: 5
Evaluation of the Antioxidant and Anticancer Activities of Hydroalcoholic Extracts of Thymus daenensis Čelak and Stachys pilifera Benth 麝香Čelak和毛蕊草水醇提取物抗氧化和抗癌活性的评价
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-03-30 DOI: 10.1155/2022/1924265
Zahra Barmoudeh, M. T. Ardakani, A. Doustimotlagh, H. Bardania
Herein, the effects of hydroalcoholic extracts of Thymus daenensis Celak (TDC) and Stachys pilifera Benth (SPB) plants on HepG2 cell line were investigated by using different analyses. Cytotoxicity and apoptosis of extracts were investigated by MTT method, AnnV/PI apoptosis assay, and their antioxidant capacity was evaluated by total thiol and glutathione peroxidase (GPX) assay. The results revealed that the SBP extract was more cytotoxic compared with the TDC extract and increased over time (128.49 µg/mL vs 107.11 µg/mL IC50 values for 24 and 72 h, respectively). Although, AnnV/PI apoptosis assay showed apoptosis induction for both extracts, but the caspase-3 activity assay revealed that TDC extract significantly increased caspase-3 activity compared with the control and SPB extract. Increasing the activity of GPX by SPB extract revealed that it has high antioxidant capacity. In conclusion, the TDC and SPB with high antioxidant capacity have high cytotoxicity against HepG2 cancer cells and have high capability as a medicinal plant.
采用不同的方法研究了胸腺草(Thymus daenensis Celak, TDC)和毛毛竹(Stachys pilifera Benth, SPB)植物水醇提取物对HepG2细胞株的影响。采用MTT法、AnnV/PI细胞凋亡法检测提取物的细胞毒性和细胞凋亡,采用总硫醇和谷胱甘肽过氧化物酶(GPX)法检测提取物的抗氧化能力。结果显示,与TDC提取物相比,SBP提取物具有更强的细胞毒性,并且随着时间的推移而增加(24和72 h的IC50值分别为128.49µg/mL和107.11µg/mL)。虽然AnnV/PI细胞凋亡实验显示两种提取物均诱导凋亡,但caspase-3活性实验显示,与对照和SPB提取物相比,TDC提取物显著提高了caspase-3活性。SPB提取物对GPX活性的提高表明其具有较高的抗氧化能力。综上所述,TDC和SPB具有较高的抗氧化能力,对HepG2癌细胞具有较高的细胞毒性,具有较高的药用价值。
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引用次数: 8
The Effect of Alcoholic Extract of Anabasis syriaca Iljin on Biochemical and Histological Parameters in Rats 丁香醇提物对大鼠生化和组织学参数的影响
IF 2.9 Q2 TOXICOLOGY Pub Date : 2022-03-24 DOI: 10.1155/2022/6945745
Suad M. Kloub, S. Banihani, O. Atrooz, W. Hananeh
This work investigates the effect of the alcoholic extract of Anabasis syriaca Iljin on biochemical and histological parameters in male rats. The lethal dose (50% of the plant extract) was assessed, and three separate doses (1/10th, 1/15th, and 1/20th) were orally gavaged for two weeks into three study groups of animals (five rats in each group), with one group used as a control and gavaged normal saline via the same route. Blood was collected after overnight fasting, and 24 biochemical parameters were evaluated. The gross and microscopic findings were reported after the collection of specimens from the animals and processed routinely for standard histological procedures. Among all tested biochemical parameters, a significant increase was noted in fasting serum glucose (p ≤ 0.010), troponin (p ≤ 0.001), and creatine kinase (p ≤ 0.001), while a significant decrease was found in triglycerides (p ≤ 0.001) and low-density lipoprotein (p=0.001). On the other hand, no significant histopathological lesions were present within the examined tissues of all groups. In conclusion, ethanolic extract of Anabasis syriaca negatively affected the cardiac function of male rats and increased their serum glucose but reduced their serum triglycerides and low-density lipoprotein.
本工作研究了丁香醇提取物对雄性大鼠生化和组织学参数的影响。评估致死剂量(植物提取物的50%),并将三个单独的剂量(1/10、1/15和1/20)分别灌胃至三个研究动物组(每组五只大鼠),为期两周,其中一组用作对照,并通过相同途径灌胃生理盐水。在禁食过夜后采集血液,并评估24个生化参数。从动物身上采集标本后报告大体和显微镜检查结果,并按照标准组织学程序进行常规处理。在所有测试的生化参数中,空腹血糖(p≤0.010)、肌钙蛋白(p≤0.001)和肌酸激酶(p≤001)显著增加,而甘油三酯(p≤.001)和低密度脂蛋白(p=0.001)显著降低。另一方面,所有组的检查组织中均未出现显著的组织病理学病变。总之,紫丁香乙醇提取物对雄性大鼠的心功能产生了负面影响,增加了它们的血糖,但降低了它们的血清甘油三酯和低密度脂蛋白。
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引用次数: 2
期刊
Journal of Toxicology
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