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Toxicological Investigations of Aristolochia longa Root Extracts 马兜铃根提取物的毒理学研究
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-11-19 DOI: 10.1155/2020/7643573
Nasreddine El Omari, Omar El Blidi, A. Bouyahya, K. Sayah, S. Bakrim, S. Fettach, R. Tahri, K. Taghzouti, O. Chokairi, M. Barkiyou
Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.
马兜铃(Aristolochia longa L.,马兜铃科)是一种草本植物,因其许多治疗优点而在替代医学中得到认可。本研究的目的是确定该植物的药物毒理学作用,以确保临床安全使用。在Wistar大鼠体内以0.8、1.25、2、2.5和5的剂量对A.longa根的水提取物进行口服毒性 g/kg/天,持续21天。在整个实验期间观察临床症状,然后测量体重变化,同时在每天给药6、11和16天后,然后在21天结束时评估选定的生化参数以及相对器官重量和肝、肾和肠组织的组织学。在21天的重复剂量下,提取物有助于对照和治疗大鼠的显著体重增加。肝和肾生物标志物的全局分析显示,从治疗的第一周到第三周,对照组和不同剂量的提取物之间显著增加,这表明提取物可能对肝和肾功能产生毒性影响。组织病理学检查证实了器官毒性,结果显示,在第16天之后,接受高剂量治疗的动物的肾脏和肝脏实质发生了更大的变化。在治疗结束时,还观察到相对较小的肠道绒毛。结论是ALAE在非长期口服给药中具有低毒潜力。然而,在高慢性口服剂量下,A.longa似乎对所测试的器官具有显著毒性。
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引用次数: 7
Formaldehyde Exposure and Its Potential Health Risk in Some Beauty Salons in Kumasi Metropolis. 库马西市部分美容院甲醛暴露及其潜在健康风险
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-11-05 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8875167
Noah Kyame Asare-Donkor, James Kusi Appiah, Vincent Torve, Ray Bright Voegborlo, Anthony Apeke Adimado

Cosmetologists may be potentially exposed to high levels of formaldehyde as a result of their exposure to formaldehyde released from the various cosmetic products used in the beauty salons. In order to assess the exposure of cosmetologists to formaldehyde, the indoor air in sixty beauty salons across the ten submetros in Kumasi were sampled to determine the formaldehyde levels and the associated noncarcinogenic human health risks. Sampling was done using System Service Innovation Incorporation air sampler model 1000i, and the MBTH spectrophotometric method was used for analysis. The mean levels of formaldehyde concentrations ranged from 88.67 to 170.67 µg/m3. Out of the sixty salons sampled, 36 salons had formaldehyde levels above the WHO permissible limit of 100 µg/m3 for an eight-hour working period and also exceeded the 55 and 9 µg/m3 for chronic and acute reference exposure limit, respectively, set by the Office of Environmental Health Hazard Assessment. The results of this study revealed that the number of customers that visit the salon in a week, number of salon services offered, and age of salon had a positive significant correlation with the level of formaldehyde determined in each salon. The health risk study also revealed that about 50% of the salons had hazard quotient (HQ) above the safety limit (HQ = 1) and may, therefore, pose health risks to cosmetologists in these salons. Results from the analysis of the questionnaire revealed that hairdressers in salons that provide the entire range of salon services captured in the study are at higher risk to the effects of formaldehyde.

美容师可能会接触到高浓度的甲醛,因为他们接触到美容院使用的各种化妆品释放的甲醛。为了评估美容师对甲醛的暴露程度,对库马西10个亚市区60家美容院的室内空气进行了采样,以确定甲醛水平和相关的非致癌性人体健康风险。采用系统服务创新公司1000i型空气采样器进行采样,采用MBTH分光光度法进行分析。甲醛平均浓度为88.67 ~ 170.67µg/m3。在抽样的60家沙龙中,有36家沙龙的甲醛水平超过了世卫组织允许的8小时工作时间100微克/立方米的限值,也分别超过了环境健康危害评估办公室设定的慢性和急性参考暴露限值55微克/立方米和9微克/立方米。本研究结果显示,一周内光顾沙龙的顾客数量、提供沙龙服务的数量和沙龙的年龄与每个沙龙的甲醛检测水平呈显著正相关。健康风险研究亦显示,约有50%的美容院的危害商(HQ)高于安全限度(HQ = 1),因此可能对美容院的美容师构成健康风险。调查问卷的分析结果显示,在提供研究中捕获的所有沙龙服务的沙龙中,理发师受到甲醛影响的风险更高。
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引用次数: 13
Determination of the Cytotoxic Effect of Different Leaf Extracts from Parinari curatellifolia (Chrysobalanaceae). 金盏花不同叶提取物细胞毒作用的测定。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-10-28 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8831545
Anesu Kundishora, Simbarashe Sithole, Stanley Mukanganyama

Despite plants being a rich source of useful chemical compounds with different pharmacological properties, some of these compounds may be toxic to humans. Parinari curatellifolia, among its other important pharmacological activities, has been shown to have significant antiproliferative activity on cancer cell lines. Toxicity studies are required to determine the safety profile of P. curatellifolia in the consideration of its potential pharmaceutical benefits as a source of lead compounds in cancer therapy. The effects of P. curatellifolia on both the integrity of the erythrocyte membrane and on normal cells were determined. The dried leaf powder of P. curatellifolia was used in serial exhaustive extraction procedures using hexane, dichloromethane, ethyl acetate, acetone, ethanol, methanol, and water as solvents in addition to extraction using DCM: methanol in equal ratio. Alkaloids, flavonoids, and saponins were isolated from the ethanol extract. The leaf extracts were tested for haemolytic activity on sheep erythrocytes at concentrations of 0.625 to 5 mg/ml. The extracts were also tested for toxicity activity on normal mammalian cells such as the BALB/c mice peritoneal cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at the concentrations of 6.3 to 50 μg/ml. In the haemolysis assays, none of the plant extracts had a significant haemolytic activity with the saponin-enriched extract having the maximum haemolytic activity of 12.2% for a concentration of 5 mg/ml. In the MTT cell viability assay, none of the 11 plant extracts had significant cytotoxicity. The water extract, however, had significant (p < 0.01) proliferative activity towards the murine immune cells at all concentrations. P. curatellifolia leaf extracts were, therefore, not toxic to both erythrocytes and immune cells, and the water extract may have immunostimulatory effects. It is concluded that P. curatellifolia leaf extracts are not toxic in vitro and, therefore, our results support the use of the plant for ethnomedicinal use.

尽管植物是具有不同药理特性的有用化合物的丰富来源,但其中一些化合物可能对人体有毒。除其他重要的药理活性外,已证明Parinari curatellifolia对癌细胞具有显著的抗增殖活性。考虑到其作为癌症治疗中先导化合物的潜在药物益处,需要进行毒性研究以确定其安全性。测定了紫苏对红细胞膜完整性和正常细胞的影响。在DCM:甲醇等比例萃取的基础上,以己烷、二氯甲烷、乙酸乙酯、丙酮、乙醇、甲醇和水为溶剂,对枯叶干粉进行了一系列穷举提取。从乙醇提取物中分离出生物碱、黄酮类化合物和皂苷。在0.625 ~ 5 mg/ml浓度下,测定了其对绵羊红细胞的溶血活性。采用MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑铵)浓度为6.3 ~ 50 μg/ml,对BALB/c小鼠腹膜细胞等正常哺乳动物细胞的毒性活性进行了测试。在溶血试验中,没有一种植物提取物具有显著的溶血活性,而富含皂苷的提取物在浓度为5 mg/ml时具有最大的溶血活性12.2%。在MTT细胞活力试验中,11种植物提取物均无明显的细胞毒性。水提物对小鼠免疫细胞的增殖活性显著(p < 0.01)。因此,紫苏叶提取物对红细胞和免疫细胞均无毒性,水提取物可能具有免疫刺激作用。本研究结果表明,紫苏叶提取物在体外无毒性,支持紫苏叶作为民族药的使用。
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引用次数: 9
Larval Cytotoxic and Subacute Toxicity of Gardenia ternifolia, Rourea coccinea, and Cassytha filiformis Used in Traditional Medicine of Benin (West Africa). 贝宁(西非)传统医药中栀子、尾蚴和茜草幼虫的细胞毒性和亚急性毒性。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-10-28 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8843575
E Agbodjento, J R Klotoé, T I Sacramento, T V Dougnon, E Déguenon, J Agbankpé, K Fabiyi, P Assogba, M-P Hounkanrin, R Akotegnon, T J Dougnon, J-M Atègbo

The use of medicinal plants in traditional medicine is a common practice in developing countries. However, this unregulated or irrational use may pose a risk of toxicity to humans in the short and/or long term. Recent studies reported interesting ethnopharmacological, antioxidant, and phytochemical data on some medicinal plants used in the traditional treatment of male infertility in Benin. Unfortunately, very little data exist on the long-repeated dose toxicity of these medicinal plants. This study was aimed at evaluating the larval cytotoxicity and subacute toxicity of the hydroethanolic extract of Cassytha filiformis whole plant, Gardenia ternifolia roots, and Rourea coccinea leaves. The subacute toxicity of these plants was evaluated in male Wistar albino rats at three different doses (200, 400, and 800 mg/kg) according to the OECD 407 guidelines. Hematological and biochemical examinations and the histological study of the liver and kidneys were carried out. Larval cytotoxicity was assessed by the sensitivity of Artemia salina larvae to different concentrations of the studied plants extracts. The mean lethal concentration (LC50) was determined by the probit method. Subacute toxicity data indicated that there was no mortality or structural alterations of the liver and kidneys in the lot of treated animals. However, significant alterations in certain hematological and biochemical parameters (hematocrit, ASAT, and uremia) were noted. These abnormalities were observed in the lot of rats treated with Rourea coccinea and Cassytha filiformis extracts. Larval cytotoxicity data indicate that the studied plants extracts are not cytotoxic (LC50 > 0.1 mg/mL). These data suggest that the use in traditional medicine of studied plants at high doses and repeated over a long period of time requires special attention.

在传统医学中使用药用植物是发展中国家的一种普遍做法。然而,这种不受管制或不合理的使用可能在短期和/或长期内对人类造成毒性风险。最近的研究报告了贝宁一些用于传统治疗男性不育症的药用植物的有趣的民族药理学、抗氧化和植物化学数据。不幸的是,关于这些药用植物的长期重复剂量毒性的数据很少。摘要本研究旨在评价长丝果全株、栀子根和鸢尾叶的氢乙醇提取物对幼虫的细胞毒性和亚急性毒性。根据OECD 407指南,以三种不同剂量(200、400和800 mg/kg)对雄性Wistar白化大鼠进行了亚急性毒性评估。进行血液学、生化检查及肝、肾组织学检查。通过对不同浓度植物提取物的敏感性来评价盐蒿幼虫的细胞毒性。采用probit法测定平均致死浓度(LC50)。亚急性毒性数据表明,在许多治疗过的动物中,没有死亡或肝脏和肾脏的结构改变。然而,某些血液学和生化参数(红细胞压积、ASAT和尿毒症)发生了显著变化。这些异常现象在大量大鼠服用鸢尾花提取物和茜草提取物后均有观察到。细胞毒性数据表明,所研究的植物提取物没有细胞毒性(LC50 > 0.1 mg/mL)。这些数据表明,在传统医学中以高剂量和长时间重复使用所研究的植物需要特别注意。
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引用次数: 8
Experience of Snakebite Envenomation by a Desert Viper in Qatar. 卡塔尔沙漠毒蛇毒蛇咬伤的经验。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-10-12 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8810741
Amr Elmoheen, Waleed Awad Salem, Mahmoud Haddad, Khalid Bashir, Stephen H Thomas

Crotaline and elapid snakebites are reported all over the world as well as in the Middle East and other countries around this region. However, data regarding snakebites and their treatment in Qatar are limited. This review paper is going to investigate the presentation and treatment of snakebite in Qatar. A good assessment helps to decide on the management of the snakebites envenomation. Antivenom and conservative management are the mainstays of treatment for crotaline snakebite. Point-of-care ultrasound (POCUS) has been suggested to do early diagnosis and treatment of soft tissue problems, such as edema and compartment syndrome, after a snakebite. The supporting data are not sufficient regarding the efficiency of POCUS in diagnosing the extent and severity of tissue involvement and its ultimate effect on the outcome. Further research is suggested in this case. Systemic complications, such as bleeding diathesis, can be managed by administering clotting factors and platelets.

在世界各地以及中东和该地区的其他国家都报道了Crotaline和elapid蛇咬伤。然而,有关卡塔尔蛇咬伤及其治疗的数据有限。这篇综述论文将调查在卡塔尔蛇咬伤的表现和治疗。良好的评估有助于决定如何处理蛇咬伤。抗蛇毒血清和保守治疗是治疗蛇咬伤的主要方法。点护理超声(POCUS)已被建议做早期诊断和治疗软组织问题,如水肿和隔室综合征,蛇咬伤后。关于POCUS在诊断组织受累程度和严重程度及其对预后的最终影响方面的有效性,支持数据并不充分。在这种情况下,建议进一步研究。全身并发症,如出血性素质,可通过施用凝血因子和血小板来控制。
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引用次数: 2
Protective Effect of Costus afer Aqueous Leaf Extract (CALE) on Low-Dose Heavy Metal Mixture-Induced Alterations in Serum Lipid Profile and Hematological Parameters of Male Wistar Albino Rats. 木香叶水提物(CALE)对低剂量重金属混合物诱导的雄性Wistar白化大鼠血脂和血液学参数变化的保护作用。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-09-29 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8850264
Brilliance O Anyanwu, Chinna N Orish, Anthonet N Ezejiofor, Ify L Nwaogazie, Orish E Orisakwe

The present work investigated the protective effects of Costus afer Ker Gawl. aqueous leaf extract (CALE) on lipid profile and hematological changes induced by exposure to low-dose heavy metal mixture in male albino rats. The experimental animals were divided into six weight matched groups. The normal (group 1) and toxic (group 2) controls received deionized water and metal mixture (20 mg/kg PbCl2, 1.61 mg/kg CdCl2, and 0.40 mg/kg HgCl2), respectively. Test rats in groups 3, 4, and 5 were treated with metal mixture and CALE (750, 1500, and 2250 mg/kg, respectively), and group 6 received metal mixture and ZnCl2. All treatments were administered through oral gavage for 12 weeks. LDHMM caused a marked increase (p < 0.05) in cholesterol, triglyceride, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels and a decrease in high-density lipoprotein (HDL), percentage body weight gain, and feed and fluid intake. Also, a significant decrease in RBC, Hb, and PCV, a significant increase in WBC, and no significant increase in platelet PLT were observed in the metal mixture-treated group. But in CALE treated groups, their levels were found to attain almost normal values as found in normal control which is also similar to the zinc-treated group. Costus afer may hold a promise in improving lipid profile and hemodynamic picture in cardiovascular diseases.

本研究探讨了木苁蓉对克尔高热后的保护作用。水叶提取物(CALE)对暴露于低剂量重金属混合物后雄性白化大鼠血脂和血液学变化的影响。实验动物被分为体重匹配的6组。正常对照组(1组)和中毒对照组(2组)分别给予去离子水和金属混合物(20 mg/kg PbCl2、1.61 mg/kg CdCl2和0.40 mg/kg HgCl2)。3、4、5组大鼠分别给予金属合剂和钙(750、1500、2250 mg/kg), 6组大鼠给予金属合剂和氯化锌。所有治疗均采用灌胃治疗,疗程12周。LDHMM显著增加了胆固醇、甘油三酯、低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL)水平(p < 0.05),降低了高密度脂蛋白(HDL)、体增重百分比、饲料和液体摄入量。此外,在金属混合物处理组中,RBC、Hb和PCV显著减少,WBC显著增加,血小板PLT无显著增加。但在cal治疗组中,它们的水平几乎达到了正常水平,就像在正常对照组中发现的那样,这也与锌治疗组相似。在改善心血管疾病的血脂和血流动力学方面,Costus可能有希望。
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引用次数: 6
Evaluation of 1-Propanol Toxicity in B6C3F1 Mice via Repeated Inhalation over 28 and 90 Days. 通过 28 天和 90 天反复吸入 1-丙醇对 B6C3F1 小鼠毒性的评估。
IF 3.4 Q2 TOXICOLOGY Pub Date : 2020-09-24 eCollection Date: 2020-01-01 DOI: 10.1155/2020/9172569
Eun-Sang Cho, Yong-Hoon Lee, Jeong-Hee Han, Sung-Jin Kim, Ka-Young Park, Ji-Min Jo, Sung-Bae Lee

We evaluated the toxicity of 1-propanol exposure following repeated inhalation over 28- and 90-day periods in male and female B6C3F1 mice to confirm the potential target organs and to determine the no-observable-adverse-effect levels (NOAELs). Five mice of each sex were exposed to 1-propanol at concentrations of 0, 100, 400, or 1600 ppm for 28 days and showed no consequent toxicity. Following this, ten mice of each sex were exposed at concentrations of 0, 500, 1600, or 5200 ppm for 90 days. We observed no effects on food consumption, body weight, organ weight, clinical signs, hematology and biochemistry parameters, or gross or histological features even at the maximum concentration. Therefore, the NOAEL of inhaled 1-propanol was defined as 5200 ppm (12.8 mg/L) for male and female mice under study conditions.

我们评估了雄性和雌性 B6C3F1 小鼠在 28 天和 90 天内反复吸入 1-丙醇的毒性,以确认潜在的靶器官并确定无观测不良效应水平(NOAELs)。每种性别的五只小鼠分别接触浓度为 0、100、400 或 1600 ppm 的 1-丙醇 28 天,结果均未显示出毒性。随后,每种雌雄小鼠各十只分别接触浓度为 0、500、1600 或 5200 ppm 的 1-丙醇,持续 90 天。我们观察到,即使在最高浓度下,小鼠的进食量、体重、器官重量、临床症状、血液学和生物化学参数、大体或组织学特征均未受到影响。因此,在研究条件下,雄性和雌性小鼠吸入 1-丙醇的无观测不良效应水平被定义为 5200 ppm(12.8 mg/L)。
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引用次数: 0
Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model. 银杏(种子)80%甲醇提取物生化成分对爪哇Medaka (Oryzias javanicus)模型胆碱酯酶的抑制作用
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-09-23 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8815313
Ibrahim Hassan, Wan Norhamidah Wan Ibrahim, Ferdaus Mohamat Yusuf, Siti Aqlima Ahmad, Syahida Ahmad

Background: Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed.

Methods: The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC).

Results: The result shows activities with high significant differences at P < 0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method.

Conclusion: The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.

背景:导致大脑和脊髓中存在的神经细胞死亡的病理生理变化被称为神经退行性疾病。目前,由于药物成本和副作用,这些疾病的治疗效果并不好,并且遇到了许多挑战。因此,寻找替代合成药物的替代品的需求很大。因此,本研究的目的是评价银杏种子的抗胆碱酯酶特性。方法:用80%甲醇提取种子。对爪哇稻鳉鱼(Oryzias javanicus)进行了毒力研究和抗胆碱酯酶活性评价。采用高效液相色谱法对粗提物进行植物化学研究,鉴定其生物活性成分。结果:治疗组与未治疗组活性差异显著,P < 0.001。用高效液相色谱法鉴定了其中的一种生物活性化合物(维他素)。结论:生物活性化合物vitaxin的存在是提高该植物提取物活性的主要次生代谢产物之一。该植物抗胆碱酯酶活性高,毒性作用低,可作为天然药物或保健品使用。
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引用次数: 7
Organophosphorus Nerve Agents: Types, Toxicity, and Treatments. 有机磷神经毒剂:类型、毒性和治疗。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-09-22 eCollection Date: 2020-01-01 DOI: 10.1155/2020/3007984
Sudisha Mukherjee, Rinkoo Devi Gupta

Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.

有机磷化合物是世界范围内广泛使用的农药,对人类健康造成极大危害。神经毒剂是有机磷化合物的一个子类,在战争中被生产和使用,它们也被用于恐怖活动。这些化合物通过相互作用和抑制乙酰胆碱酯酶而导致胆碱能危机,具有生理威胁。本文综述了有机磷化合物胆碱能和非胆碱能作用的机制。有机磷中毒的可能治疗策略是不同类型的生物清除剂,包括化学计量,催化和伪催化。目前对有前景的治疗方法的研究,特别是催化生物清除剂,包括几种野生型有机磷酸盐水解酶,如对氧磷酶和磷酸三酯酶、磷酸三酯酶样内酯酶、甲基对硫磷水解酶、有机磷酸脱氢酶、二异丙基氟磷酸酶、人三磷酸核苷酸水解酶和衰老标记蛋白等,已经得到了广泛的讨论。据报道,有机磷化合物是许多哺乳动物有机磷水解酶的非生理底物;因此,这些酶对这些化合物的效率是不足的。因此,已经进行了研究,以创建具有更高水解率和高特异性的突变体。应用定向分子进化和/或靶向诱变已经产生了一些突变体,并对催化效率进行了表征。一般来说,有机磷化合物本质上是手性的。这篇综述也广泛讨论了突变酶的发展,以提供更好的立体选择性降解有毒有机磷化合物。现有的酶显示出有限的效率;因此,更有效的治疗策略也被批判性地分析。
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引用次数: 45
Cytotoxicity Potential of Endophytic Fungi Extracts from Terminalia catappa against Human Cervical Cancer Cells. 刺尾草内生真菌提取物对人宫颈癌细胞的细胞毒性潜力。
IF 2.9 Q2 TOXICOLOGY Pub Date : 2020-09-22 eCollection Date: 2020-01-01 DOI: 10.1155/2020/8871152
Michèle Stella Majoumouo, Marius Belmondo Tincho, Rufin Marie Kouipou Toghueo, Thureyah Morris, Donavon Charles Hiss, Fabrice Fekam Boyom, Chitra Mandal

Endophytic fungi are potential sources of novel bioactive metabolites from a natural product drug discovery perspective. This study reports the bioactivity-directed fractionation of the secondary metabolites of the ethyl acetate extract of a fermentation culture of endophytic fungi from Terminalia catappa which were then evaluated for their cytotoxicity against human cervical cancer (HeLa) cells and human foreskin fibroblast (HFF) cells. Furthermore, apoptosis was determined using the Annexin V/propidium iodide (PI) flow cytometry assay. Endophyte extracts N2, N7, N8, N97, N169, and N233 were obtained from Trichoderma sp, Phoma sp, Phomopsis phyllanticola, Fusarium oxyporum, Collectotrichum sp, and Cryptococcus flavescens, respectively. The N97 extract was most active with a 50% inhibitory concentration (IC50) of 33.35 µg/ml. A 50% cytotoxic concentration (CC50) of 268.4 µg/ml was obtained with HFF cells and the selectivity index (SI) was 8.01. The percentages of cell populations were increased at late apoptosis (Annexin+/PI+), with the percentages of 27.4 ± 0.3 and 19.2 ± 0.01 obtained, respectively, for 50 µg/ml and 80 µg/ml of the N97 extract and 2.1 ± 0.1 obtained for the control in late apoptosis (Annexin V+/PI+) . Moreover, a higher reduction in the percentage of viable cells was observed in the HeLa control cells (93.6 ± 0.3), but the percentages of viable HeLa cells were 37 ± 0.05 and 45 ± 0.1, respectively, for the 50 µg/ml and 80 µg/ml treatments with the N97 extract. Also, the percentages of 34.7 ± 0.1 and 33.9 ± 0.4 were, respectively, obtained for 50 µg/ml and 80 µg/ml compared to the control with 4.6 ± 0.2, in early apoptosis (Annexin V+/PI-). These findings highlight the anticancer potential of the N97 extract of endophytic fungi from Terminalia catappa, which is mediated through apoptosis and presumably also attenuation of chemoresistance.

从天然产物药物发现的角度来看,内生真菌是新型生物活性代谢物的潜在来源。本研究报道了以生物活性为导向的对刺尾草内生真菌发酵培养物乙酸乙酯提取物次级代谢物的分离,并对其对人宫颈癌(HeLa)细胞和人包皮成纤维细胞(HFF)细胞的细胞毒性进行了评价。此外,采用Annexin V/碘化丙啶(PI)流式细胞术检测细胞凋亡。从木霉(Trichoderma sp)、Phoma sp、phyllanticola Phomopsis sp、oxyporum Fusarium、Collectotrichum sp和隐球菌(Cryptococcus flavescens)中分别获得内生菌提取物N2、N7、N8、N97、N169和N233。N97提取物活性最高,50%抑制浓度(IC50)为33.35µg/ml。HFF细胞的细胞毒浓度(CC50)为268.4µg/ml,选择性指数为8.01。凋亡晚期(Annexin+/PI+)细胞群百分比增加,50µg/ml和80µg/ml N97提取物组细胞群百分比分别为27.4±0.3和19.2±0.01,对照组细胞群百分比分别为2.1±0.1。此外,在HeLa对照细胞中,活细胞百分比下降幅度较大(93.6±0.3),而在N97提取物50µg/ml和80µg/ml处理下,HeLa活细胞百分比分别为37±0.05和45±0.1。在早期凋亡(Annexin V+/PI-)中,50µg/ml和80µg/ml的比例分别为34.7±0.1和33.9±0.4,而对照组为4.6±0.2。这些发现强调了刺麻内生真菌N97提取物的抗癌潜力,这种潜力可能是通过细胞凋亡介导的,也可能是通过抑制化学耐药性来实现的。
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引用次数: 16
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Journal of Toxicology
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