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In vitro acute inhalation toxicity for TiO2 (GST) using 3D human tissue model (EpiAirwayTM). 利用3D人体组织模型(EpiAirwayTM)研究TiO2 (GST)的体外急性吸入毒性。
Pub Date : 2021-09-01 Epub Date: 2021-07-20 DOI: 10.5620/eaht.2021015
Seong Yong Jang, Myeong Kyu Park, Jae Min Im, Hae Sung Park, Heung Sik Seo, Hee Ju Park, Sung Soon Nah

The present study was performed to screen in vitro potential acute inhalation toxicity using an EpiAirwayTM tissue model (human tracheal/bronchial tissue) for the nano-sized titanium dioxide, GST manufactured as a photocatalyst through of sludge recycling and to compare with P-25 a commercialized photocatalytic material. According to the protocol provided by in vitro tissue manufacturer, the GST was exposure to the tissue for 3 hours in 450, 500, 650, 850 mg/mL concentration after preliminary dose range finding study and then tissue viability (%, IC75) was calculated using the MTT assay. Besides, the histopathological observation was performed to compare to the MTT assay. As a result of study, IC75 could not be confirmed at 850 mg/mL in both GST and P-25 and the grade was confirmed to be IC75> 600 mg/mL in vitro model tissue category. Therefore, it was considered that the GHS category could be classified as 'No classification' in screening method for potential acute inhalation toxicity. Also, not the morphological effects of epithelial cells in tissue model were observed compared with the vehicle control and histological findings were similar to the results of MTT Viability assay. Based on these results, the potential acute inhalation toxicity for GST produced through sludge recycling using in vitro tissue model inhalation toxicity showed that it could be non-hazardous substance. However, further study (in vivo study, etc.) is thought to be needed to ascertain whether GST is a toxic effect or safe.

本研究使用EpiAirwayTM组织模型(人体气管/支气管组织)筛选纳米二氧化钛的体外急性吸入毒性,GST通过污泥回收作为光催化剂制造,并与商业化光催化材料P-25进行比较。根据体外组织制造商提供的方案,在初步剂量范围研究后,将GST以450、500、650、850 mg/mL的浓度暴露于组织3小时,然后使用MTT法计算组织活力(%,IC75)。同时进行组织病理学观察,与MTT法进行比较。研究结果表明,GST和P-25在850 mg/mL时均不能确定IC75,体外模型组织类IC75> 600 mg/mL。因此,在潜在急性吸入毒性的筛选方法中,GHS类别可归为“无分类”。组织模型中上皮细胞的形态学变化与对照比较,组织学结果与MTT活力测定结果相似。基于这些结果,利用体外组织模型吸入毒性对污泥回收产生的GST的潜在急性吸入毒性表明它可能是非有害物质。然而,需要进一步的研究(体内研究等)来确定GST是有毒的还是安全的。
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引用次数: 4
Acute toxicity assessment for TiO2 photocatalyst (GST) made from wastewater using TiCl4 in rat. 利用 TiCl4 从废水中提取的二氧化钛光催化剂(GST)对大鼠的急性毒性评估。
Pub Date : 2021-09-01 Epub Date: 2021-08-12 DOI: 10.5620/eaht.2021019
Ja Kyung Seol, Myeongkyu Park, Jae Min Im, Heung Sik Seo, Hee Ju Park, Sung Soon Nah

TiO2 was a photocatalyst that used to the most common product because of the high efficiency. TiO2 (P-25, commercial nanomaterial product) is the most typical photocatalyst product and TiO2 (GST) was a sludge recycling product. This study was reported to evaluate an acute toxicity of TiO2 (P-25 and GST) according to OECD test guideline 402 and 423 in Sprague-Dawley (SD) female rats via route of oral and dermal. There was investigated the lethal dose (LD50), and mortality, clinical signs, body weight changes and gross findings were continually monitored for 14 days following the single administration. After administration, TiO2 (P-25) was calculated that LD50 was considered to be a dose of over 2000 mg/kg body weight for both different route of exposure, and TiO2 (GST) was the same. Other items were no observed an adverse effect between P-25 and GST; no mortality and clinical signs, accidental body weight loss, no gross findings. On the basis of the above results, the toxicity of the GST was almost equal to that of the commercial product, P-25 and there was no toxicological evidence.

TiO2 是一种光催化剂,因其效率高而成为最常见的产品。TiO2(P-25,商业纳米材料产品)是最典型的光催化剂产品,TiO2(GST)是污泥回收产品。本研究报告根据经合组织测试准则 402 和 423,通过口服和皮肤途径对二氧化钛(P-25 和 GST)在斯普拉格-道利(SD)雌性大鼠体内的急性毒性进行了评估。研究了致死剂量(LD50),并在一次给药后的 14 天内持续监测死亡率、临床症状、体重变化和大体结果。给药后计算得出,TiO2(P-25)的半数致死剂量为两种不同接触途径的剂量均超过 2000 毫克/千克体重,TiO2(GST)也是如此。其他项目没有观察到 P-25 和 GST 之间的不良影响;没有死亡和临床症状,体重意外减轻,没有大体检查结果。根据上述结果,GST 的毒性与商用产品 P-25 几乎相同,没有毒理学证据。
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引用次数: 0
Gastrointestinal tract and skin permeability of chemicals in consumer products using parallel artificial membrane permeability assay (PAMPA). 使用平行人工膜渗透性测定法(PAMPA)测定消费品中化学物质的胃肠道和皮肤渗透性。
Pub Date : 2021-09-01 Epub Date: 2021-09-27 DOI: 10.5620/eaht.2021021
Juyoung Park, Handule Lee, Kwangsik Park

Some chemicals commonly used in personal care products, household items, food vessels, cosmetics, and other consumer products are potentially harmful, and several reviews of epidemiological studies have suggested the associations between the chemical exposure from consumer products, and respiratory diseases, skin sensitization, and reproductive problems. Therefore, risk assessment is essential for management of consumer products safety. Necessarily, the estimation of human exposure is an essential step in risk assessment, and the absorption rate of those chemicals via the gastrointestinal tract, respiratory tract, and skin are very critical in determining the internal dose of the exposed chemicals. In this study, parallel artificial membrane permeability assays (PAMPA) for the gastrointestinal tract and skin were performed to evaluate the permeability of parabens (4-hydroxybenzoic acid, methyl-, propyl-, and butyl paraben), bisphenols (bisphenol A, bisphenol F, and bisphenol S), isothiazolinones (methyl-, chloromethyl-, benz-, octyl-, and dichlorooctyl isothiazolinone), and phthalates [diethyl-, dibutyl-, Di-isononyl-, and bis(2-ethylhexyl) phthalate]. Lipid solubility of test chemicals indicated by log P values was shown as the most critical factor and showed a positive association with the permeability of parabens, bisphenols, and isothiazolinones in PAMPA assay. However, phthalate showed a reverse-association between lipophilicity and permeability. The permeability of all the tested chemicals was higher in the gastrointestinal tract membrane than in the skin membrane. The pH in donor solution did not show significant effects on the permeability in all the chemicals, except the chemicals with a free hydrophilic moiety in their chemical structures.

个人护理产品、家庭用品、食品容器、化妆品和其他消费品中常用的一些化学物质可能有害,对流行病学研究的几项综述表明,消费品中的化学物质暴露与呼吸系统疾病、皮肤过敏和生殖问题之间存在关联。因此,风险评估对消费品安全管理至关重要。人体暴露量的估算是风险评估中必不可少的一步,而这些化学物质经胃肠道、呼吸道和皮肤的吸收率对于确定暴露化学物质的内剂量至关重要。在这项研究中,对胃肠道和皮肤进行了平行人工膜渗透性测定(PAMPA),以评估对羟基苯甲酸酯(4-羟基苯甲酸,甲基-,丙基-和丁基对羟基苯甲酸酯),双酚类(双酚A,双酚F和双酚S),异噻唑啉酮(甲基-,氯甲基-,苯-,辛-和二氯辛基异噻唑啉酮)和邻苯二甲酸酯[二乙基-,二丁基-,二异ononyl-和双(2-乙基己基)邻苯二甲酸酯]的渗透性。通过对数P值表示的测试化学物质的脂溶性是最关键的因素,并且在PAMPA分析中显示与对羟基苯甲酸酯、双酚类和异噻唑啉酮的通透性呈正相关。然而,邻苯二甲酸酯在亲脂性和渗透性之间表现出相反的关系。所有被测化学物质在胃肠道膜的渗透性都高于皮肤膜。供体溶液的pH值对所有化学物质的渗透性均无显著影响,但化学结构中有游离亲水部分的化学物质除外。
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引用次数: 5
Evaluation of potential eye or skin irritation/corrosion in rabbit exposed to TiO2 photocatalyst (GST). 评价暴露于TiO2光催化剂(GST)的家兔潜在的眼睛或皮肤刺激/腐蚀。
Pub Date : 2021-09-01 Epub Date: 2021-09-28 DOI: 10.5620/eaht.2021022
Sang Ho Kim, Myeong Kyu Park, Ja Kyung Seol, Jae Min Im, Hae Sung Park, Heung Sik Seo, Hee Ju Park, Sung Soon Nah

TiO2 NPs photocatalyst is widely used in a variety of applications and products in the environmental and energy fields, including self-cleaning surfaces, air and water purification systems, sterilization, hydrogen evolution, and photoelectrochemical conversion. The possible biological and safety effects of TiO2 dermal exposure and absorption have not been well studied and more investigations on the potential health hazards of the TiO2 are needed. This study aimed to investigate potential effect of local lesions (eye and skin irritation/corrosion) for new TiO2 material powder, GST produced through sludge recycling of the sewage treatment plant in according to the OECD test guideline (TG 404, 405) and imaging evaluation (micro-computed tomography analysis), histopathology examination. Also, P-25, commercial photocatalyst was used to compare with GST. For the eye or skin irritation/corrosion test, the test substances (GST, P-25) showed no irritation/corrosion for local lesions and the GHS category was identified as a "No hazard class". The imaging analysis indicated that GST did not penetrate or distribute in the local lesions (eye, skin) and the treatment-related effect was not observed in histopathology. Therefore, the present study revealed that new TiO2 powder, GST was considered to be no potential effects (irritation/corrosion), penetration or distribution in the local lesions (eye, skin).

TiO2 NPs光催化剂广泛应用于环境和能源领域的各种应用和产品中,包括自清洁表面、空气和水净化系统、杀菌、析氢和光电化学转化。TiO2皮肤暴露和吸收可能产生的生物和安全影响尚未得到很好的研究,需要对TiO2的潜在健康危害进行更多的调查。本研究旨在根据OECD测试指南(TG 404405)和成像评估(微型计算机断层扫描分析)、组织病理学检查,研究新TiO2材料粉末、污水处理厂污泥回收产生的GST的局部损伤(眼睛和皮肤刺激/腐蚀)的潜在影响。此外,使用商业光催化剂P-25与GST进行比较。对于眼睛或皮肤刺激/腐蚀测试,测试物质(GST,P-25)显示局部损伤没有刺激/腐蚀,GHS类别被确定为“无危险类别”。影像学分析表明,GST没有渗透或分布在局部病变(眼睛、皮肤)中,在组织病理学中也没有观察到与治疗相关的效果。因此,本研究表明,新型TiO2粉末GST被认为在局部病变(眼睛、皮肤)中没有潜在影响(刺激/腐蚀)、渗透或分布。
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引用次数: 5
Effects of carbamate pesticides intermediates on Escherichia coli membrane architecture: An in vitro and in silico approach. 氨基甲酸酯类农药中间体对大肠杆菌膜结构的影响:体外和室内研究。
Pub Date : 2021-09-01 Epub Date: 2021-08-25 DOI: 10.5620/eaht.2021020
Pushpendra Singh, Manish Kumar Tripathi, Mohammad Yasir, Ashish Ranjan, Rahul Shrivastava

Methyl isocyanate (MIC), a low molecular weight synthetic aliphatic compound, having an isocyanate group (-NCO), has industrial application. In this study, the effects of methyl isocyanate and its mechanism on outer membrane protein of Escherichia coli were observed using experimental and computational methods. In vitro exposure of N-succinimidyl N-methylcarbamate (NSNM) a synthetic analogue of MIC on E. coli to a final concentration of 2 mM was found to affect the growth curve pattern and changes in cell morphology. Molecular docking studies of MIC and NSNM with E. coli outer membrane protein (OmpW, OmpX, OmpF OmpA), and periplasmic domain (PAL) were performed. The in-silico results revealed that outer membrane protein OmpF showed the highest negative binding energy, i.e. ∆G -4.11 kcal/mole and ∆G -3.19 kcal/mole by NSNM and MIC as compared to other proteins. Our study concludes that methyl isocyanate retains lethal toxicity which leads to cell death due to the membrane protein damage of E. coli membrane.

异氰酸甲酯(Methyl isoocyanate, MIC)是一种具有异氰酸基(-NCO)的低分子量合成脂肪族化合物,具有工业应用价值。本研究采用实验和计算相结合的方法,观察了异氰酸甲酯对大肠杆菌外膜蛋白的影响及其作用机制。n -琥珀酰氨基酰基n -甲基氨基甲酸酯(NSNM)是一种合成的MIC在大肠杆菌上的类似物,在体外暴露于终浓度为2 mM时,可以影响生长曲线模式和细胞形态的变化。进行了MIC和NSNM与大肠杆菌外膜蛋白(OmpW、OmpX、OmpF OmpA)和质周结构域(PAL)的分子对接研究。结果表明,与其他蛋白相比,NSNM和MIC作用下外膜蛋白OmpF的负结合能最高,分别为∆G -4.11 kcal/mol和∆G -3.19 kcal/mol。我们的研究表明,异氰酸甲酯保留了致命毒性,导致大肠杆菌膜蛋白损伤导致细胞死亡。
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引用次数: 2
Comparison of mice' sperm parameters exposed to some hazardous physical agents. 小鼠精子参数与暴露于某些有害物理介质的小鼠精子参数的比较。
Pub Date : 2021-09-01 Epub Date: 2021-07-13 DOI: 10.5620/eaht.2021013
Mohammad-Bagher Abdollahi, Somayeh Farhang Dehghan, Faezeh Abasi Balochkhaneh, Manouchehr Ahmadi Moghadam, Hamzeh Mohammadi

The present study was aimed to compare the effects of exposure to noise, vibration, lighting, and microwave on male mice' sperm parameters. The mice were randomly assigned to five groups of eight, which comprised of the unexposed group and exposure groups including the lighting (1000 lux), noise (100 dB(A)), vibration (acceleration of 1.2 m/s2) and microwave (power density of 5 watts). The exposure groups were subjected to the four agents for 8 hours a day, 5 days a week during a 2-week period. Semen analysis were done according to World Health Organization guidelines. The highest significant mean difference in sperm count (-1.35×106/mL) had being observed between the microwave group and the control one (P=0.001). The highest difference in immotile percent (25.88 %) had being observed between the noise group and the control one (P=0.001). The highest difference in normal morphology (-27.06 %) observed between the lighting exposure group and the control group (P=0.001). The four agents can cause changes in different sperm parameters, however for definite conclusion; more laboratory and field studies are required. In total, exposure to microwave has had the greatest effect on sperm count and exposure to light has had the greatest effect on normal morphology and non-progressive motility. Moreover, exposure to noise has had the greatest effect on progressive motility and immotile percent, respectively.

本研究旨在比较暴露于噪声、振动、照明和微波对雄性小鼠精子参数的影响。小鼠被随机分配到五组,每组八只,包括未暴露组和暴露组,暴露组包括照明(1000 勒克斯)、噪音(100 分贝(A))、振动(加速度为 1.2 米/秒2)和微波(功率密度为 5 瓦)。在为期两周的时间里,暴露组每周 5 天、每天 8 小时受到这四种制剂的影响。精液分析根据世界卫生组织的指导方针进行。微波组与对照组的精子数量平均差异最大(-1.35×106/毫升)(P=0.001)。噪音组与对照组的不育率差异最大(25.88%)(P=0.001)。照明组与对照组的正常形态差异最大(-27.06 %)(P=0.001)。这四种物质会导致精子的不同参数发生变化,但要得出明确的结论,还需要进行更多的实验室和实地研究。总之,暴露于微波对精子数量的影响最大,暴露于光照对正常形态和非进行性运动的影响最大。此外,暴露于噪声中对精子活动力和不活动精子百分比的影响最大。
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引用次数: 0
Identification of heavy metals source within selected active dumpsites in southeastern Nigeria. 在尼日利亚东南部选定的活跃垃圾场内确定重金属来源。
Pub Date : 2021-06-01 Epub Date: 2021-05-24 DOI: 10.5620/eaht.2021008
Valentine Ifenna Onwukeme, Victor Chukwuemeka Eze

Discriminating contaminant sources is crucial for pollution control. The study aimed at identifying the source(s) of heavy metals in active dumpsite soils from selected areas in Southeastern Nigeria using statistical tools. The dumpsites were Enyimba dumpsite Aba (dumpsite-1), Okpuno-Egbu dumpsite Nnewi (dumpsite-2), Rice mill dumpsite Abakaliki (dumpsite-3) and Nekede dumpsite Owerri (dumpsite-4) in Abia, Anambra, Ebonyi and Imo State respectively. After standard sampling, elemental analysis was carried out using an energy dispersive x-ray fluorescence spectrometer; Chromium (Cr), Manganese (Mn), Cobalt (Co), Iron (Fe), Nickel (Ni), Copper (Cu), Zinc (Zn), Arsenic (As), Lead (Pb) and Cadmium (Cd) were quantified and results showed they were present in high concentrations above control and standard values set by the National Environmental Standards and Regulations Enforcement Agency (NESREA) and the Food and Agriculture Organization of the United Nations (FAO) / World Health Organization (WHO). Metals investigated exhibited variable correlations among themselves suggesting potential multi-element contamination, while soil organic matter (OM) and pH displayed both significant positive and negative influence on the metal availability in the studied soils. Test of significance of the observed correlation were positive and significant (r > 0.9 at p < 0.05/0.01) for Cr/Co, Cr/Fe, Mn/Co, Co/Fe, Cu/Zn, Zn/Pb, Cu/As, Cu/Pb, Zn/As, As/Pb in dumpsite-1; in dumpsite-2, only Ni/Cu; in dumpsite-3, Fe/OM and Cd/OM while in dumpsite-4,Co/Fe, Cu/As, Cu/Pb, Zn/Cd, Ni/OM, and As/Pb. Hierarchical cluster analysis (HCA) and Principal component analysis (PCA) extracted two to three components/groups based on square Euclidean distance and eigenvalues > 1, confirming sources to be from organic pigments in plastics, scrap metals and incinerated biodegradable wastes. This study concludes that statistical methods can provide a scientific basis for monitoring heavy metals accumulation in dumpsite soils.

辨别污染源是控制污染的关键。该研究旨在利用统计工具确定尼日利亚东南部选定地区活跃垃圾场土壤中重金属的来源。倾倒场分别为阿比亚州、阿南布拉州、埃邦伊州和伊莫州的恩尼姆巴倾倒场阿坝(倾倒场-1)、奥克普诺-埃格布倾倒场Nnewi(倾倒场-2)、碾米厂倾倒场Abakaliki(倾倒场-3)和Nekede倾倒场Owerri(倾倒场-4)。标准取样后,使用能量色散x射线荧光光谱仪进行元素分析;对铬(Cr)、锰(Mn)、钴(Co)、铁(Fe)、镍(Ni)、铜(Cu)、锌(Zn)、砷(As)、铅(Pb)和镉(Cd)进行了量化,结果显示它们的浓度高于国家环境标准和法规执行机构(NESREA)和联合国粮食及农业组织(FAO) /世界卫生组织(WHO)设定的控制和标准值。土壤有机质(OM)和pH值对土壤金属有效性既有正向影响,也有负向影响。垃圾场-1中Cr/Co、Cr/Fe、Mn/Co、Co/Fe、Cu/Zn、Zn/Pb、Cu/As、Cu/Pb、Zn/As、As/Pb的相关性均呈显著性正相关(r > 0.9, p < 0.05/0.01);在垃圾场-2中,只有Ni/Cu;3号垃圾场有Fe/OM和Cd/OM, 4号垃圾场有Co/Fe、Cu/As、Cu/Pb、Zn/Cd、Ni/OM和As/Pb。层次聚类分析(HCA)和主成分分析(PCA)根据欧几里得距离的平方和特征值> 1提取出2 ~ 3个成分/基团,确定其来源为塑料、废金属和焚烧生物可降解废物中的有机颜料。研究结果表明,统计方法可为垃圾场土壤重金属积累监测提供科学依据。
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引用次数: 14
Toxicity assessment of dimethyl carbonate following 28 days repeated inhalation exposure. 重复吸入28天后碳酸二甲酯的毒性评估。
Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.5620/eaht.2021012
Dongseok Seo

Dimethyl carbonate (DMC) has been used as a reagent in methylation reactions, can be used as paints, coatings, and adhesives, and is a chemical that is being used increasing, which poses a health hazard to workers who handle it. So, the toxic reactions of F344 rats with inhalation exposure to 600, 1600, and 5000 ppm concentrations for 6 hours, 5 days a week, 4 weeks was evaluated. During the exposure period, general signs were observed, body weight and food consumption were measured, and hematologic and blood biochemical tests, organ weight measurements, necropsy, and histopathological examination were performed after the end of exposure. During the exposure period, dimethyl carbonate was exposed to an average of 599.26±31.40, 1614.64±80.79 and 5106.83±297.13 ppm in the chambers of the T1, T2 and T3 test groups, respectively. During the test period, general signs, weight change, food consumption, organ weight measurement, necropsy, and histopathological examination did not show any effects related to exposure to the test substance. However, as a result of blood and blood biochemical tests, an increase in AST, ALP, APTT, and PT levels was observed. From these results, it is judged that liver is the target organ when repeated inhalation exposure of dimethyl carbonate, the test substance, for 4 weeks, and the exposure-related effects of the test substance were observed at PT and ALP levels up to 600 ppm exposure concentration, but NOEC (No Observed Effect Concentration) was determined to be less than 600 ppm because it was not judged as an adverse effect.

碳酸二甲酯(DMC)已被用作甲基化反应的试剂,可用作油漆、涂料和粘合剂,而且是一种使用越来越多的化学品,对接触它的工人构成健康危害。因此,我们评估了F344大鼠吸入600、1600和5000 ppm浓度6小时,每周5天,4周的毒性反应。暴露期间观察一般体征,测量体重和食量,暴露结束后进行血液学和血液生化检查、器官重量测量、尸检和组织病理学检查。在暴露期间,T1、T2和T3试验组的试验室内碳酸二甲酯的平均暴露量分别为599.26±31.40、1614.64±80.79和5106.83±297.13 ppm。在试验期间,一般体征、体重变化、食物消耗、器官重量测量、尸检和组织病理学检查均未显示与暴露于试验物质有关的任何影响。然而,作为血液和血液生化测试的结果,观察到AST, ALP, APTT和PT水平升高。从这些结果可以判断,当试验物质碳酸二甲酯连续4周反复吸入暴露时,肝脏是靶器官,并且在高达600ppm暴露浓度的PT和ALP水平下观察到试验物质的暴露相关效应,但NOEC(未观察到的效应浓度)被确定为小于600ppm,因为它不被判断为不良效应。
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引用次数: 1
Fibrosis as a result of polyhexamethylene guanide exposure in cultured Statens Seruminstitut Rabbit Cornea (SIRC) cells. 在培养的Statens Seruminstitut兔角膜(SIRC)细胞中暴露于聚六亚甲基胍导致的纤维化。
Pub Date : 2021-06-01 Epub Date: 2021-06-07 DOI: 10.5620/eaht.2021009
Handule Lee, Juyoung Park, Kwangsik Park

Previous research studies on the toxicity of polyhexamethylene guanidine (PHMG) as a humidifier disinfectant majorly focused on lung fibrosis. Considering that disinfectants in humidifiers are released in aerosol form, the eyes are directly exposed and highly vulnerable to the detrimental effects of the PHMG. Therefore, in the present study we investigated the adverse effects of PHMG on the eyes; considering fibrosis as a manifestation of PHMG toxicity in the eye, we evaluated fibrosis-related biomarkers in cultured Statens Seruminstitut Rabbit Cornea (SIRC) cells. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, fibrosis-related biomarkers were evaluated through polymerase chain reaction (PCR) and immunoblotting, and oxidative stress was evaluated using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Polyhexamethylene guanidine showed cytotoxicity in a time and concentration-dependent manner. Fibrosis related biomarkers including transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and hemeoxygenase-1 (HO-1) increased in both gene and protein levels. Oxidative stress also increased in the PHMG-treated cultured cells. The findings of the present study suggest that PHMG could cause toxicity in the eye as manifested by fibrosis.

以往关于聚六亚甲基胍(PHMG)作为加湿器消毒剂毒性的研究主要集中在肺纤维化方面。考虑到加湿器中的消毒剂以气溶胶形式释放,眼睛直接暴露,极易受到PHMG的有害影响。因此,在本研究中,我们研究了PHMG对眼睛的不良影响;考虑到纤维化是PHMG对眼睛毒性的一种表现,我们在培养的Statens Seruminstitut兔角膜(SIRC)细胞中评估了纤维化相关的生物标志物。采用3-(4,5-二甲基噻唑-2-基)- 2,5 -二苯基溴化四唑(MTT)法检测细胞活力,采用聚合酶链反应(PCR)和免疫印迹法检测纤维化相关生物标志物,采用2',7'-二氯二氢荧光素(H2DCFDA)检测氧化应激。聚六亚甲基胍具有时间和浓度依赖性的细胞毒性。纤维化相关生物标志物包括转化生长因子-β (TGF-β)、α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶(MMP)、金属蛋白酶组织抑制剂(TIMP)和血红素加氧酶-1 (HO-1)的基因和蛋白水平均升高。氧化应激在phmg处理的培养细胞中也有所增加。本研究结果表明,PHMG可引起眼睛毒性,表现为纤维化。
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引用次数: 5
Blocking the interactions between human ACE2 and coronavirus spike glycoprotein by selected drugs: a computational perspective. 通过选择药物阻断人类ACE2与冠状病毒刺突糖蛋白之间的相互作用:计算视角
Pub Date : 2021-06-01 Epub Date: 2021-06-14 DOI: 10.5620/eaht.2021010
Chidi Edbert Duru, Haruna Isiyaku Umar Umar, Ijeoma Akunna Duru, Uchechi Emmanuela Enenebeaku, Lynda Chioma Ngozi-Olehi, Christian Ebere Enyoh

The coronavirus disease of 2019 (COVID-19) has become a global pandemic with rapid rate of transmission and fatalities worldwide. Scientists have been investigating a host of drugs that may be rechanneled to fight this malaise. Thus, in this current computational study we carried out molecular docking experiments to assess the bridging potentials of some commercial drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, camostat, famotidine, umifenovir, nitazoxanide, ivermectin, and fluvoxamine at the interface between human ACE2 and the coronavirus spike glycoprotein complex. This is aimed at ascertaining the ability of these drugs to bridge and prevent the complexing of these two proteins. The crystal structure of human ACE2 and the coronavirus spike glycoprotein complex was retrieved from protein database, while the selected drugs were retrieved from PubChem data base. The proteins and drugs were prepared for docking using Cresset Flare software. The docking was completed via AutoDock Vina module in Python Prescription software. The best hit drugs with each receptor were selected and their molecular interactions were analyzed using BIOVIA's Discovery Studio 2020. The best hit compounds on the human ACE2 were the lopinavir (-10.1 kcal/mol), ritonavir (-8.9 kcal/mol), and nafamostat (-8.7 kcal/mol). Ivermectin, nafamostat, and camostat with binding energy values -9.0 kcal/mol, -7.8 kcal/mol, and -7.4 kcal/mol respectively were the hit drugs on the coronavirus spike glycoprotein. Nafamostat showed a dual bridging potential against ACE2 and spike glycoprotein, and could therefore be a promising lead compound in the prevention and control of this disease.

2019年冠状病毒病(COVID-19)已成为全球大流行,在世界范围内传播速度快,死亡人数多。科学家们一直在研究一系列可以用来对抗这种不适的药物。因此,在当前的计算研究中,我们进行了分子对接实验,以评估一些商业药物如氯喹、羟氯喹、洛匹那韦、利托那韦、那莫他、卡莫他、法莫替丁、乌米诺韦、尼唑昔尼德、伊维菌素和氟伏沙明在人ACE2和冠状病毒刺突糖蛋白复合物界面上的桥接电位。这是为了确定这些药物的能力,以桥和防止这两个蛋白质的络合。人类ACE2和冠状病毒刺突糖蛋白复合物的晶体结构从蛋白质数据库中检索,所选药物从PubChem数据库中检索。利用Cresset Flare软件对蛋白质和药物进行对接制备。对接通过Python Prescription软件中的AutoDock Vina模块完成。选择每种受体的最佳药物,并使用BIOVIA的Discovery Studio 2020分析它们的分子相互作用。洛匹那韦(-10.1 kcal/mol)、利托那韦(-8.9 kcal/mol)和那莫他(-8.7 kcal/mol)对ACE2的影响最大。伊维菌素、那莫司他和卡莫司他的结合能分别为-9.0 kcal/mol、-7.8 kcal/mol和-7.4 kcal/mol,是对冠状病毒刺突糖蛋白的靶向药物。Nafamostat显示出对ACE2和刺突糖蛋白的双重桥接潜力,因此可能是预防和控制该疾病的有希望的先导化合物。
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引用次数: 6
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Environmental analysis, health and toxicology
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