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Protective effects of resveratrol against fumonisin B1-induced liver toxicity in mice. 白藜芦醇对伏马菌素b1诱导的小鼠肝毒性的保护作用。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-06-01 DOI: 10.2478/aiht-2023-74-3648
Rıza Yalçın, Asım Kart, Özlem Özmen, Esra Zeybek

The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity.

本研究的目的是研究白藜芦醇对伏马毒素B1 (FB1)诱导的肝毒性的作用,因为据我们所知,这些作用尚未被研究过,尽管FB1的毒性作用和机制以及白藜芦醇的抗氧化作用是众所周知的。40只BALB/c小鼠分为对照组、FB1组、白藜芦醇组和FB1+白藜芦醇组。对照组接受生理盐水治疗14天。FB1组每隔一天给予2.25 mg/kg FB1,连用14 d。白藜芦醇组给予白藜芦醇10 mg/kg,连续14 d。FB1+白藜芦醇组每隔一天给药2.25 mg/kg FB1,每隔一天给药10 mg/kg白藜芦醇,连续14 d。所有给药均为腹膜。分析血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总唾液酸(TSA)水平,测定肝脏中总抗氧化状态(TAS)和总氧化状态(TOS)。此外,检查肝组织的组织病理学变化。FB1组AST、ALT、TSA显著高于对照组。白藜芦醇对所有参数(包括TOS和TAS)均有抵抗FB1的作用。肝脏组织学显示fb1诱导的部分肝细胞充血、浸润和巨核增生。对照组、白藜芦醇组和FB1+白藜芦醇组均未见病理变化。我们的研究结果证实了白藜芦醇对FB1引起的肝损伤和氧化应激的保护作用。此外,他们认为血清TSA水平升高可以作为fb1诱导的肝毒性的生物标志物。
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引用次数: 0
The effects of ketamine on viability, primary DNA damage, and oxidative stress parameters in HepG2 and SH-SY5Y cells. 氯胺酮对HepG2和SH-SY5Y细胞活力、原代DNA损伤和氧化应激参数的影响
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-06-01 DOI: 10.2478/aiht-2023-74-3727
Andreja Jurič, Blanka Tariba Lovaković, Antonio Zandona, Dubravka Rašić, Martin Češi, Alica Pizent, Marijana Neuberg, Irena Canjuga, Maja Katalinić, Ana Lucić Vrdoljak, Arnes Rešić, Irena Brčić Karačonji

Ketamine is a dissociative anaesthetic used to induce general anaesthesia in humans and laboratory animals. Due to its hallucinogenic and dissociative effects, it is also used as a recreational drug. Anaesthetic agents can cause toxic effects at the cellular level and affect cell survival, induce DNA damage, and cause oxidant/antioxidant imbalance. The aim of this study was to explore these possible adverse effects of ketamine on hepatocellular HepG2 and neuroblastoma SH-SY5Y cells after 24-hour exposure to a concentration range covering concentrations used in analgesia, drug abuse, and anaesthesia (0.39, 1.56, and 6.25 µmol/L, respectively). At these concentrations ketamine had relatively low toxic outcomes, as it lowered HepG2 and SH-SY5Y cell viability up to 30 %, and low, potentially repairable DNA damage. Interestingly, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) remained unchanged in both cell lines. On the other hand, oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] pointed to ketamine-induced oxidant/antioxidant imbalance.

氯胺酮是一种解离性麻醉剂,用于人类和实验动物的全身麻醉。由于其致幻和解离作用,它也被用作娱乐性药物。麻醉药可引起细胞水平的毒性作用,影响细胞存活,诱导DNA损伤,引起氧化/抗氧化失衡。本研究的目的是探讨氯胺酮对肝细胞HepG2和神经母细胞瘤SH-SY5Y细胞在24小时暴露于包括镇痛、药物滥用和麻醉的浓度范围(分别为0.39、1.56和6.25µmol/L)后可能产生的不良影响。在这些浓度下,氯胺酮具有相对较低的毒性结果,因为它将HepG2和SH-SY5Y细胞的活力降低了30%,并且降低了潜在可修复的DNA损伤。有趣的是,两种细胞系的活性氧(ROS)、丙二醛(MDA)和谷胱甘肽(GSH)水平保持不变。另一方面,氧化应激标志物[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)]指向氯胺酮诱导的氧化/抗氧化失衡。
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引用次数: 0
The PNPLA family of enzymes: characterisation and biological role. PNPLA酶家族:表征和生物学作用。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-06-01 DOI: 10.2478/aiht-2023-74-3723
Ana-Marija Lulić, Maja Katalinić

This paper brings a brief review of the human patatin-like phospholipase domain-containing protein (PNPLA) family. Even though it consists of only nine members, their physiological roles and mechanisms of their catalytic activity are not fully understood. However, the results of a number of knock-out and gain- or loss-of-function research models suggest that these enzymes have an important role in maintaining the homeostasis and integrity of organelle membranes, in cell growth, signalling, cell death, and the metabolism of lipids such as triacylglycerol, phospholipids, ceramides, and retinyl esters. Research has also revealed a connection between PNPLA family member mutations or irregular catalytic activity and the development of various diseases. Here we summarise important findings published so far and discuss their structure, localisation in the cell, distribution in the tissues, specificity for substrates, and their potential physiological role, especially in view of their potential as drug targets.

本文综述了人类类专利磷脂酶结构域蛋白(PNPLA)家族的研究进展。尽管它仅由9个成员组成,但它们的生理作用和催化活性机制尚不完全清楚。然而,许多敲除和获得或失去功能的研究模型的结果表明,这些酶在维持细胞器膜的稳态和完整性、细胞生长、信号传导、细胞死亡和脂质代谢(如三酰基甘油、磷脂、神经酰胺和视黄酰基酯)方面发挥着重要作用。研究还揭示了PNPLA家族成员突变或不规则催化活性与各种疾病的发生之间的联系。在这里,我们总结了迄今为止发表的重要发现,并讨论了它们的结构、在细胞中的定位、在组织中的分布、对底物的特异性以及它们潜在的生理作用,特别是考虑到它们作为药物靶点的潜力。
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引用次数: 0
Energy and emission properties of burley tobacco stalk briquettes and its combinations with other biomass as promising replacement for coal. 毛烟草茎块的能量和排放特性及其与其他生物质的组合作为煤炭替代品的前景。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-04-04 Print Date: 2023-03-01 DOI: 10.2478/aiht-2023-74-3630
Maja Malnar, Vesna Radojičić, Gordana Kulić, Zoran Dinić, Olga Cvetković

As a tobacco producer, Serbia has to deal with large amounts of leftover tobacco stalks after harvesting. One option for this type of biomass is to burn it, but burning is not encouraged in Serbia, since the levels of its combustion products have not been investigated yet. The aim of this study was therefore to determine the elemental composition, ash and nicotine content, heat values, and composition of gaseous combustion products of tobacco stalk briquettes and to see if their mixing with other types of biomass available in Serbia could improve their ecological profile. We made 11 different types of briquettes: six of pure raw materials, including burley tobacco stalks, sunflower head remains, wheat straw, corncob, soy straw, and beech sawdust and five by mixing tobacco stalks with these other raw materials in a 50:50 mass ratio. All briquettes meet the ecological criteria regarding the emission limits for nitrogen oxides (NOx), sulphur dioxide, carbon monoxide, and carbon dioxide. Nicotine content in flue gases (<10 mg/kg) is far below the maximum level allowed by the European Union. Heat values of all biomass samples are acceptable, although lower than those specified for solid biofuels (≥16.0 MJ/kg), save for corncob and beech sawdust and their mixtures with tobacco stalks. Our findings therefore encourage the use of tobacco stalks as a viable biofuel.

作为烟草生产国,塞尔维亚必须处理大量收获后剩余的烟草茎秆。处理这类生物质的一种方法是焚烧,但塞尔维亚不鼓励焚烧,因为尚未对其燃烧产物的含量进行调查。因此,本研究的目的是确定烟草茎秆压块的元素组成、灰分和烟碱含量、热值以及气体燃烧产物的组成,并研究将其与塞尔维亚现有的其他类型生物质混合是否能改善其生态状况。我们制作了 11 种不同类型的煤球:6 种是纯原料,包括烟梗、向日葵头残留物、小麦秸秆、玉米芯、大豆秸秆和山毛榉锯屑;5 种是将烟梗与这些其他原料以 50:50 的质量比混合。所有煤砖都符合氮氧化物(NOx)、二氧化硫、一氧化碳和二氧化碳排放限值的生态标准。烟气中的尼古丁含量 (
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引用次数: 1
Different damaging effects of volatile anaesthetics alone or in combination with 1 and 2 Gy gamma-irradiation in vivo on mouse liver DNA: a preliminary study. 体内挥发性麻醉剂单独或与 1 和 2 Gy 伽马射线照射相结合对小鼠肝脏 DNA 的不同破坏作用:一项初步研究。
IF 1.7 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-04-04 Print Date: 2023-03-01 DOI: 10.2478/aiht-2023-74-3692
Vesna Benković, Mirta Milić, Nada Oršolić, Anica Horvat Knežević, Gordana Brozović, Nikola Borojević

As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment.

随着放射治疗和放射诊断程序数量的逐年增加,全身挥发性麻醉(VA)的使用也在增加。尽管挥发性麻醉被认为是安全的,但它的暴露会导致不同的不良反应,与电离辐射(IR)结合使用时还会产生协同效应。然而,人们对在单次放疗中使用这种组合剂量所造成的 DNA 损伤知之甚少。为了了解更多相关信息,我们使用彗星试验评估了瑞士白化雄性小鼠在单独或与 1 或 2 Gy 照射结合使用异氟醚(I)、七氟醚(S)或氟烷(H)后肝组织中的 DNA 损伤和修复反应。在照射后立即(0 小时)、2、6 和 24 小时取样。与对照组相比,单独接受氟烷或同时接受 1 或 2 Gy IR 照射的小鼠 DNA 损伤最高。七氟醚和异氟醚对1 Gy IR有保护作用,而对2 Gy IR的不利影响则出现在暴露后24小时。虽然VA的影响取决于肝脏的新陈代谢,但在与2 Gy红外联合照射24小时后检测到未修复的DNA损伤表明,我们需要进一步研究VA和红外对基因组稳定性的联合影响,并将单次照射和重复照射的时间范围从24小时延长到更长的时间范围,从而使放射治疗的情况更符合实际。
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引用次数: 0
Genotoxic and genoprotective effects of 1,4-dihydropyridine derivatives: a brief review. 1,4-二氢吡啶衍生物的基因毒性和基因保护作用:综述。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-03-01 DOI: 10.2478/aiht-2023-74-3707
Elina Leonova, Nadezhda Ryabokon, Evita Rostoka, Vitalijs Borisovs, Astrida Velena, Egils Bisenieks, Gunars Duburs, Maija Dzintare, Roza Goncharova, Nikolajs Sjakste
Abstract This review summarises current knowledge about the genotoxic and genoprotective effects of 1,4-dihydropyridines (DHP) with the main focus on the water-soluble 1,4-DHPs. Most of these water-soluble compounds manifest very low calcium channel blocking activity, which is considered “unusual” for 1,4-DHPs. Glutapyrone, diludine, and AV-153 decrease spontaneous mutagenesis and frequency of mutations induced by chemical mutagens. AV-153, glutapyrone, and carbatones protect DNA against the damage produced by hydrogen peroxide, radiation, and peroxynitrite. The ability of these molecules to bind to the DNA may not be the only mechanism of DNA protection, as other mechanisms such as radical scavenging or binding to other genotoxic compounds may take place and enhance DNA repair. These uncertainties and reports of high 1,4-DHP concentrations damaging the DNA call for further in vitro and in vivo preclinical research, pharmacokinetic in particular, as it can help pinpoint the exact mechanism(s) of the genotoxic and/or genoprotective action of 1,4-DHPs.
本文综述了目前关于1,4-二氢吡啶(DHP)基因毒性和基因保护作用的研究进展,重点介绍了水溶性的1,4-二氢吡啶。大多数水溶性化合物表现出非常低的钙通道阻断活性,这对于1,4- dhp来说是“不寻常的”。谷胱甘肽、二吡啶和AV-153降低了化学诱变剂诱导的自发诱变和突变频率。AV-153、谷胱甘肽和碳酮保护DNA免受过氧化氢、辐射和过氧亚硝酸盐产生的损伤。这些分子与DNA结合的能力可能不是DNA保护的唯一机制,因为其他机制,如自由基清除或与其他基因毒性化合物的结合可能会发生并增强DNA修复。这些不确定性和高1,4- dhp浓度损害DNA的报告需要进一步的体外和体内临床前研究,特别是药代动力学研究,因为它可以帮助查明1,4- dhp基因毒性和/或基因保护作用的确切机制。
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引用次数: 0
A study on the relationship between sociodemographic characteristics and job stress and satisfaction among healthcare workers in Turkey during the COVID-19 pandemic. 2019冠状病毒病大流行期间土耳其医护人员社会人口学特征与工作压力和满意度的关系研究
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-03-01 DOI: 10.2478/aiht-2023-74-3672
Hasan Tuna, Osman Oğulcan Türkmen, Sirer Albayrak

The aim of this study was to determine the sociodemographic characteristics that affect job stress and job satisfaction in 454 healthcare workers (physicians, nurses, midwives, technicians, and other healthcare personnel) working with COVID-19 patients in primary healthcare institutions in Turkey with a cross-sectional, web-based survey between 9 and 30 August 2021. The survey included a personal information form, a standard job stress scale, and the Minnesota Satisfaction Questionnaire. The levels of job stress and job satisfaction did not differ between male and female respondents. Singles reported lower job stress and higher job satisfaction than the married respondents. Job stress did not differ between departments, but respondents on the front line who worked in a COVID-19 intensive care unit (ICU) (at any point and/or at the time of the study) or the emergency department reported lower job satisfaction than those working in other departments. Similarly, while stress did not differ by educational status, satisfaction of respondents with bachelor's or master's degree was lower than that of the rest. Our findings also suggest that working in a COVID-19 ICU and age are significant predictors of higher stress, whereas lower education, working in a COVID-19 ICU, and being married are good predictors of lower satisfaction. Further research should include other sociodemographic variables that may affect stress and satisfaction at work, and similar studies should follow up to see what was left in the wake of the pandemic.

本研究的目的是在2021年8月9日至30日期间,通过一项基于网络的横断面调查,确定影响土耳其初级卫生保健机构中与COVID-19患者一起工作的454名卫生保健工作者(医生、护士、助产士、技术人员和其他卫生保健人员)工作压力和工作满意度的社会人口统计学特征。该调查包括个人信息表、标准工作压力量表和明尼苏达满意度问卷。男性和女性受访者的工作压力和工作满意度水平没有差异。与已婚受访者相比,单身人士的工作压力更小,工作满意度更高。不同部门的工作压力没有差异,但在COVID-19重症监护病房(ICU)工作的一线受访者(在研究的任何时候和/或在研究期间)或急诊科的工作满意度低于在其他部门工作的受访者。同样,尽管压力并不因教育程度而异,但拥有学士或硕士学位的受访者的满意度低于其他受访者。我们的研究结果还表明,在COVID-19重症监护室工作和年龄是压力较高的重要预测因素,而教育程度低、在COVID-19重症监护室工作和已婚是满意度较低的良好预测因素。进一步的研究应包括可能影响工作压力和满意度的其他社会人口变量,并应开展类似的研究,以了解大流行之后还剩下什么。
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引用次数: 0
Short-term effects of air pollution on hospital admissions for cardiovascular diseases and diabetes mellitus in Sofia, Bulgaria (2009-2018). 保加利亚索非亚空气污染对心血管疾病和糖尿病住院人数的短期影响(2009-2018年)。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-03-01 DOI: 10.2478/aiht-2023-74-3704
Angel M Dzhambov, Krasimira Dikova, Tzveta Georgieva, Teodor I Panev, Plamen Mukhtarov, Reneta Dimitrova

Bulgaria has a very high incidence of cardiometabolic diseases and air pollution-related mortality rate. This study investigated the relationship between daily air pollution levels and hospital admissions for ischaemic heart diseases (IHD), cerebral infarction (CI), and type 2 diabetes mellitus (T2DM) in Sofia, Bulgaria. We obtained daily data on hospitals admissions and daily average air pollution levels from 2009 to 2018. Pollutants of interest were particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3), and carbon monoxide (CO). Negative binomial regressions were fitted to study the effects of air pollution on hospital admission over the course of seven days prior to that event, accounting for autocorrelations and time trend in the data, day of the week, temperature, and relative humidity. Our findings confirm that higher air pollution levels generally increase the risk of hospital admissions for IHD and CI. For T2DM the association is less clear. Admissions often lagged several days behind and were more common in specific demographic subgroups or when pollution crossed a particular threshold. However, we did not expect to find the risk of hospital admissions increased in warmer rather than colder months of the year. Our findings are to be taken with reservation but do provide an idea about how air pollution could trigger acute episodes of related cardiovascular diseases, and our model may serve to investigate similar associations across the country.

保加利亚的心脏代谢疾病发病率和与空气污染有关的死亡率非常高。本研究调查了保加利亚索非亚每日空气污染水平与缺血性心脏病(IHD)、脑梗死(CI)和2型糖尿病(T2DM)住院率之间的关系。我们获得了2009年至2018年的每日住院人数和每日平均空气污染水平的数据。我们关注的污染物包括颗粒物(PM2.5和PM10)、二氧化氮(NO2)、二氧化硫(SO2)、臭氧(O3)和一氧化碳(CO)。采用负二项回归来研究空气污染对事件发生前7天内住院人数的影响,考虑到数据中的自相关性和时间趋势、星期几、温度和相对湿度。我们的研究结果证实,较高的空气污染水平通常会增加IHD和CI住院的风险。对于2型糖尿病,这种关联就不太清楚了。入院人数往往会落后几天,在特定的人口亚群中或污染超过特定阈值时更为常见。然而,我们没有预料到在一年中温暖的月份而不是寒冷的月份住院的风险会增加。我们的研究结果是有保留的,但确实提供了一个关于空气污染如何引发相关心血管疾病急性发作的想法,我们的模型可能有助于调查全国各地的类似关联。
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引用次数: 0
The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats. 辛伐他汀和非诺贝特对正常血脂和高血脂大鼠血浆、肝脏和脑中丙二醛和还原性谷胱甘肽浓度的影响
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-03-01 DOI: 10.2478/aiht-2023-74-3697
Antonija Vukšić, Dubravka Rašić, Suzana Žunec, Tamara Božina, Paško Konjevoda, Jasna Lovrić, Marinko Bilušić, Vlasta Bradamante

The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.

本研究旨在探讨不同剂量辛伐他汀和非诺贝特对正常血脂和高血脂雄性大鼠血浆、肝脏和脑组织中丙二醛(MDA)和还原性谷胱甘肽(GSH)的影响。正常血脂(Wistar)大鼠每天接受10或50 mg/kg辛伐他汀或30或50 mg/kg非诺贝特。高脂血症(Zucker)大鼠接受50 mg/kg/天辛伐他汀或30 mg/kg/天非诺贝特。正常血脂和高脂血症对照大鼠给予生理盐水。辛伐他汀、非诺贝特、生理盐水灌胃3周。在正常血脂大鼠中,辛伐他汀和非诺贝特对血浆和脑MDA和GSH浓度的影响相似且剂量无关。血浆和脑MDA降低,脑GSH浓度升高。在高脂血症大鼠中,辛伐他汀不影响血浆和脑MDA和GSH浓度,但显著降低肝脏GSH。非诺贝特降低血浆和肝脏MDA,但增加脑MDA。在这两种大鼠菌株中,非诺贝特显著降低了肝脏GSH浓度,很可能是因为非诺贝特的代谢物与GSH结合。我们的研究结果表明,辛伐他汀仅在正常血脂大鼠中起抗氧化作用,而非诺贝特在两种大鼠品系中都起抗氧化作用。
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引用次数: 0
New in vitro findings about halogenated boroxine cytotoxicity and deregulation of cell death-related genes in GR-M melanoma cells. 在GR-M黑色素瘤细胞中卤化硼氧素细胞毒性和细胞死亡相关基因调控的体外新发现。
IF 2.1 4区 医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Pub Date : 2023-03-01 DOI: 10.2478/aiht-2023-74-3702
Nikolina Elez-Burnjaković, Lejla Pojskić, Anja Haverić, Naida Lojo-Kadrić, Maida Hadžić Omanović, Jasmin Ramić, Ajla Smajlović, Milka Maksimović, Sanin Haverić

Anti-proliferative effects of halogenated boroxine - K2(B3O3F4OH) (HB) - have been confirmed in multiple cancer cell lines, including melanoma, but the exact mechanism of action is still unknown. This study aimed to determine its cytotoxic effects on human Caucasian melanoma (GR-M) cell growth in vitro as well as on the expression of cell death-related genes BCL-2, BECN1, DRAM1, and SQSTM1. GR-M and peripheral blood mononuclear (PBM) cells were treated with different HB concentrations and their growth inhibition and relative gene expression profiles were determined using the Alamar blue assay and real-time PCR. HB significantly inhibited cell growth of both GR-M and PBM cells but was even more effective in GR-M melanoma cells, as significant inhibition occurred at a lower HB concentration of 0.2 mg/mL. GR-M BCL-2 expression was significantly downregulated (P=0.001) at HB concentration of 0.4 mg/mL, which suggests that HB is a potent tumour growth inhibitor. At the same time, it upregulated BCL-2 expression in normal (PBM) cells, probably by activating protective mechanisms against induced cytotoxicity. In addition, all but the lowest HB concentrations significantly upregulated SQSTM1 (P=0.001) in GR-M cells. Upregulated BECN1 expression suggests early activation of autophagy at the lowest HB concentration in SQSTM1 cells and at all HB concentrations in PBM cells. Our findings clearly show HB-associated cell death and, along with previous cytotoxicity studies, reveal its promising anti-tumour potential.

卤代硼氧素- K2(B3O3F4OH) (HB) -在包括黑色素瘤在内的多种癌细胞系中具有抗增殖作用,但其确切的作用机制尚不清楚。本研究旨在确定其对人类高加索黑色素瘤(GR-M)细胞体外生长的细胞毒性作用,以及对细胞死亡相关基因BCL-2、BECN1、DRAM1和SQSTM1表达的影响。用不同浓度的HB处理GR-M细胞和外周血单核细胞(PBM),采用Alamar蓝法和实时荧光定量PCR检测其生长抑制和相关基因表达谱。HB显著抑制GR-M细胞和PBM细胞的生长,但在GR-M黑色素瘤细胞中更有效,因为在0.2 mg/mL较低的HB浓度下发生显著抑制。HB浓度为0.4 mg/mL时,GR-M BCL-2表达显著下调(P=0.001),提示HB是一种有效的肿瘤生长抑制剂。同时,它上调了正常细胞(PBM)中BCL-2的表达,可能是通过激活针对诱导细胞毒性的保护机制。此外,除了最低的HB浓度外,所有HB浓度都显著上调GR-M细胞中的SQSTM1 (P=0.001)。BECN1表达上调表明,在最低HB浓度的SQSTM1细胞和所有HB浓度的PBM细胞中,自噬被早期激活。我们的研究结果清楚地显示了hb相关的细胞死亡,并与之前的细胞毒性研究一起揭示了其有希望的抗肿瘤潜力。
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引用次数: 0
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Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology
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