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Trace elements exposure and risk in age-related eye diseases: a systematic review of epidemiological evidence. 微量元素暴露与老年性眼病风险:流行病学证据系统综述
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 Epub Date: 2021-06-11 DOI: 10.1080/26896583.2021.1916331
Onyinyechi Bede-Ojimadu, Chinna N Orish, Beatrice Bocca, Flavia Ruggieri, Chiara Frazzoli, Orish E Orisakwe

This systematic review aimed to evaluate existing evidence on the associations between trace elements exposure and age-related eye diseases. PubMed and Google scholar databases were searched for epidemiological and postmortem studies on the relationship between exposure to trace elements and Age-related eye diseases such as age-related macular degeneration (AMD), cataract, glaucoma and diabetic retinopathy (DR), in population groups aged 40 years and above. Available evidence suggests that cadmium (Cd) exposure may be positively associated with the risks of AMD and cataract. There is also evidence that exposure to lead (Pb) may be positively associated with higher risk of cataract and glaucoma. There is limited number of relevant studies and lack of prospective studies for most of the investigated associations. Evidence for other trace elements is weak and inconsistent, and the number of available studies is small. Likewise, there are very few relevant studies on the role of trace elements in DR. Chemical elements that affect the distribution and absorption of other trace elements have never been investigated. The suggestive but limited evidence motivates large and quality prospective studies to fully characterize the impact of exposure to trace (toxic and essential) elements on age-related eye diseases.

本系统综述旨在评估微量元素暴露与年龄相关性眼病之间关系的现有证据。在PubMed和Google学者数据库中检索了40岁及以上人群中微量元素暴露与年龄相关性眼病(如年龄相关性黄斑变性(AMD)、白内障、青光眼和糖尿病性视网膜病变(DR))之间关系的流行病学和尸检研究。现有证据表明,镉(Cd)暴露可能与黄斑变性和白内障的风险呈正相关。也有证据表明,接触铅(Pb)可能与白内障和青光眼的高风险呈正相关。相关的研究数量有限,而且大多数被调查的关联缺乏前瞻性研究。其他微量元素的证据薄弱且不一致,现有的研究数量很少。同样,关于微量元素在dr中的作用的相关研究也很少,影响其他微量元素分布和吸收的化学元素从未被研究过。这些具有启发性但有限的证据促使进行大量高质量的前瞻性研究,以充分描述接触微量(有毒和必需)元素对与年龄相关的眼病的影响。
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引用次数: 4
Ecotoxicological effects of dietary titanium dioxide nanoparticles on metabolic and biochemical parameters of model organism Galleria mellonella (Lepidoptera: Pyralidae). 饲粮中二氧化钛纳米颗粒对模式生物黑粉蚧代谢和生化参数的生态毒理学影响
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 Epub Date: 2021-09-09 DOI: 10.1080/26896583.2021.1969846
Serkan Sugeçti, Benay Tunçsoy, Ender Büyükgüzel, Pınar Özalp, Kemal Büyükgüzel

Nanoparticles (NPs) are now being used in many industrial activities, such as mining, paint and glass industries. The frequent industrial use of NPs contributes to environmental pollution and may cause cellular and oxidative damage in native organisms. In this study, the toxic effects of titanium dioxide nanoparticles (TiO2 NPs) were investigated using Galleria mellonella larvae as a model insect species. Alterations in cell damage indicators, such as alanine transferase, aspartate transferase, lactate dehydrogenase, non-enzymatic antioxidants and biochemical parameters, were determined in the hemolymph of G. mellonella larvae exposed to TiO2 NPs at different concentrations (5, 50, 250 and 1250 μg/mL) in their diets. TiO2 NPs caused concentration-dependent cellular damage in the hemolymph of G. mellonella larvae and increased the levels of the non-enzymatic antioxidants uric acid and bilirubin. In addition, total protein in hemolymph significantly decreased at the highest concentration (1250 μg/mL) of TiO2 NPs. Level of the urea increased at the highest concentration (1250 μg/mL) of TiO2 NPs, whereas the amount of glucose was not affected. These findings demonstrated that TiO2 NPs caused concentration-dependent toxic effects on G. mellonella larvae.

纳米粒子(NPs)现在被用于许多工业活动,如采矿、油漆和玻璃工业。NPs的频繁工业使用会造成环境污染,并可能导致原生生物的细胞和氧化损伤。本研究以大黄蜂幼虫为模型昆虫,研究了二氧化钛纳米颗粒(TiO2 NPs)的毒性作用。研究了不同浓度TiO2 NPs(5、50、250和1250 μg/mL)对黄颡鱼幼鱼血淋巴中丙氨酸转移酶、天冬氨酸转移酶、乳酸脱氢酶、非酶抗氧化剂及生化指标的影响。TiO2 NPs在大黄蜂幼虫血淋巴中引起浓度依赖性细胞损伤,并增加非酶抗氧化剂尿酸和胆红素的水平。当TiO2 NPs浓度达到最高(1250 μg/mL)时,血淋巴总蛋白显著降低。TiO2 NPs浓度最高(1250 μg/mL)时,尿素水平升高,而葡萄糖含量不受影响。这些结果表明TiO2 NPs对大黄蜂幼虫具有浓度依赖性的毒性作用。
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引用次数: 4
Sub-acute exposure to Sudan IV-adulterated palm oil induces oxidative stress and represses the expression of Nrf2 and antioxidant genes in male albino rats. 亚急性暴露于苏丹4号掺假棕榈油可诱导氧化应激并抑制雄性白化大鼠Nrf2和抗氧化基因的表达。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 Epub Date: 2021-08-24 DOI: 10.1080/26896583.2021.1965851
Ofem E Eteng, Ceaser A Moses, Emmanuel I Ugwor, Joe E Enobong, Adio J Akamo, Dorcas I Akinloye, Irene O Sadiku, Arikpo Iwara, Eyong Ubana

This study investigated the effects of Sudan IV dye (S4D) on antioxidant biomarkers using palm oil adulterated with S4D. Thirty male albino rats were grouped into five (n = 6); Normal control, palm oil (PO), PO + S4D (100 mg/kg), PO + S4D (250 mg/kg), and S4D (250 mg/kg) for 21 days. Oxidative stress biomarkers were assessed in the serum, liver, and kidneys. Exposure to S4D (alone and in adulterated PO) occasioned significant depletions in the activities of SOD, CAT, and GPx, as well as GSH levels in the assessed compartments. Contrastingly, the levels of NO and MDA were significantly (p < 0.05) increased in the serum, liver, and kidney of rats exposed to PO + S4D (both doses) and S4D (250 mg/kg) when compared to control rats. Further, the expressions of the genes coding for CAT, GPx-1, GSR, and Nrf-2 were significantly (p < 0.05) down-regulated, relative to β-actin, in groups exposed to S4D compared to the control. Interestingly, these parameters were not significantly different (p > 0.05) in the unadulterated PO-exposed rats compared to the control. These results show that S4D depleted the antioxidant capacities, while potentiating the generation of reactive species and oxidative damage. This study provides useful information on the oxidative mechanisms associated with consumption of S4D-containing consumer products.

本研究利用掺入S4D的棕榈油,研究了苏丹IV染料(S4D)对抗氧化生物标志物的影响。雄性白化大鼠30只,每组5只(n = 6);正常对照,棕榈油(PO), PO + S4D (100 mg/kg), PO + S4D (250 mg/kg), S4D (250 mg/kg),持续21天。在血清、肝脏和肾脏中评估氧化应激生物标志物。暴露于S4D(单独和掺假PO)引起SOD, CAT和GPx活性的显著减少,以及评估室中GSH水平的降低。与对照组相比,未掺入po的大鼠一氧化氮和丙二醛水平显著升高(p p p > 0.05)。这些结果表明,S4D降低了抗氧化能力,同时促进了活性物质的产生和氧化损伤。这项研究提供了与消费含s4d消费品有关的氧化机制的有用信息。
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引用次数: 0
Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity. 细胞色素P450s (CYP)过表达HepG2细胞的特性及其对药物和化学物质诱导的肝毒性的评估。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 DOI: 10.1080/26896583.2021.1880242
Si Chen, Qiangen Wu, Xilin Li, Dongying Li, Nan Mei, Baitang Ning, Montserrat Puig, Zhen Ren, William H Tolleson, Lei Guo

Hepatic metabolism catalyzed by the cytochrome P450 (CYP) superfamily affects liver toxicity associated with exposures to natural compounds and xenobiotic agents. Previously we generated a battery of HepG2-derived stable cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). In this study, we comprehensively characterized each cell line for its CYP expression and enzyme activity. Specifically, we measured the mRNA expression, protein expression, and metabolite formation. Using CYP3A4, 2D6, and 2C9-overexpressing cells as representatives, we examined the stability of these cells in long-term cultures for up to 10 passages. The results showed that CYPs can be stably overexpressed for up to 10 cell culture passages without losing their activities. The robustness of responses to stimuli among the cells at different passages was also investigated in CYP3A4-overexpressing cells and the response to amiodarone and dronedarone showed no difference between the cells at the passage 2 and 10. Moreover, the mRNA expression level of most CYPs was higher in CYP-overexpressing HepG2 cells than that in HepaRG cells and primary human hepatocytes. This study confirmed the stability of CYP-overexpressing HepG2 cell lines and provided useful information for a broader use of these cells in pharmacologic and toxicologic research.

细胞色素P450 (CYP)超家族催化的肝脏代谢影响与暴露于天然化合物和外源药物相关的肝毒性。在此之前,我们构建了一组hepg2衍生的稳定细胞系,分别表达14种CYPs (1A1、1A2、1B1、2A6、2B6、2C8、2C9、2C18、2C19、2D6、2E1、3A4、3A5和3A7)。在这项研究中,我们全面表征了每个细胞系的CYP表达和酶活性。具体来说,我们测量了mRNA表达、蛋白质表达和代谢物形成。以CYP3A4、2D6和2c9过表达细胞为代表,我们检测了这些细胞在长达10代的长期培养中的稳定性。结果表明,CYPs可以稳定过表达长达10个细胞培养代而不失去其活性。在cyp3a4过表达的细胞中,研究了不同传代细胞对刺激反应的稳健性,在传代2和10时,细胞对胺碘酮和drone - edarone的反应没有差异。此外,大多数CYPs的mRNA表达水平在过表达cyp的HepG2细胞中高于HepaRG细胞和人原代肝细胞。本研究证实了cypp过表达HepG2细胞系的稳定性,为这些细胞在药理学和毒理学研究中的广泛应用提供了有用的信息。
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引用次数: 14
Three dimensional graphene materials doped with heteroatoms for extraction and adsorption of environmental pollutants in wastewater. 掺杂杂原子的三维石墨烯材料对废水中环境污染物的提取和吸附。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 Epub Date: 2021-02-07 DOI: 10.1080/26896583.2020.1863725
Zhiyong Guo, Yufeng Feng, Chen Zhang, Guihua Huang, Jinxin Chi, Qiuhong Yao, Guofeng Zhang, Xi Chen

Environmental pollution by heavy metal ions, organic pollutants, oils, pesticides or dyes is a ubiquitous problem adversely affecting human health and environmental ecology. Development and application novel adsorbents in full-scale treatment systems with effectiveness properties could effective ways to facilitate the extraction and adsorption of environment pollutants from wastewater. Graphene materials have drawn much attention due to their extraordinary electron mobilities, high surface areas, good thermal conductivities, and excellent mechanical properties. Three-dimensional graphene materials can provide the inherent advantages of 2D graphene sheets and exhibit micro/nanoporous structures, increased specific surface areas, high electron conductivities, fast mass transport kinetics, and strong mechanical strength. Potential applications for 3D graphene materials include environmental remediation, chemical and biological sensing, catalysis, and super capacitors. Recent advances in the applications of 3D functionalized graphene materials (3D FGMs) doped with heteroatoms for the extraction and adsorption of environmental pollutants in wastewater are summarized in this review.

重金属离子、有机污染物、油类、农药或染料等对环境的污染是一个普遍存在的问题,对人类健康和环境生态造成了不利影响。新型吸附剂的开发和应用可有效地促进废水中环境污染物的提取和吸附。石墨烯材料因其优异的电子迁移率、高的比表面积、良好的导热性和优异的机械性能而备受关注。三维石墨烯材料具有二维石墨烯片的固有优点,具有微孔/纳米孔结构、增加的比表面积、高的电子导电性、快速的质量传递动力学和强的机械强度。3D石墨烯材料的潜在应用包括环境修复、化学和生物传感、催化和超级电容器。本文综述了掺杂杂原子的三维功能化石墨烯材料(3D FGMs)在废水中环境污染物的提取和吸附中的应用研究进展。
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引用次数: 3
miR-30d-5p represses the proliferation, migration, and invasion of lung squamous cell carcinoma via targeting DBF4. miR-30d-5p通过靶向DBF4抑制肺鳞状细胞癌的增殖、迁移和侵袭。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2021-01-01 Epub Date: 2021-06-24 DOI: 10.1080/26896583.2021.1926855
Yitian Qi, Yi Hou, Liangchen Qi

Objective: This study aims to explore the mechanism of miR-30d-5p in regulating the development of lung squamous cell carcinoma (LUSC) via targeting DBF4.

Methods: Bioinformatics methods were employed to analyze the differentially expressed genes in LUSC tissue microarray. qRT-PCR was employed to detect the expression of miR-30d-5p and DBF4 mRNA in normal human bronchial epithelial cells and LUSC cells. CCK-8 was used to detect LUSC cell activity. Wound healing assay was employed to detect the migratory ability of LUSC cells. Transwell was employed to detect invasive ability. Dual-luciferase reporter assay was used to detect the targeting relationship between miR-30d-5p and DBF4. Western blot was used to detect the protein expression of marker molecules associated with epithelial-mesenchymal transition (EMT).

Results: In this study, the expression of miR-30d-5p in LUSC cell lines was found to be obviously low compared with that in normal human bronchial epithelial cell line, which was opposite to the expression of DBF4. Dual-luciferase reporter assay verified that miR-30d-5p could target DBF4 and the overexpression of miR-30d-5p downregulated the expression of DBF4. Overexpression of DBF4 promoted the proliferation, migration, invasion, and EMT of LUSC, whereas over-expression of miR-30d-5p could weaken the promotion of DBF4 on cancer cells.

Conclusion: miR-30d-5p downregulates the expression of DBF4 to regulate the development of LUSC.

目的:本研究旨在探讨miR-30d-5p通过靶向DBF4调控肺鳞状细胞癌(LUSC)发生发展的机制。方法:采用生物信息学方法对LUSC组织芯片中差异表达基因进行分析。采用qRT-PCR检测miR-30d-5p和DBF4 mRNA在正常人支气管上皮细胞和LUSC细胞中的表达。CCK-8检测LUSC细胞活性。采用创面愈合实验检测LUSC细胞的迁移能力。采用Transwell检测侵入能力。采用双荧光素酶报告基因法检测miR-30d-5p与DBF4的靶向关系。Western blot检测上皮-间质转化(epithelial-mesenchymal transition, EMT)相关标记分子的蛋白表达。结果:本研究发现,miR-30d-5p在LUSC细胞系中的表达明显低于正常人支气管上皮细胞系,与DBF4的表达相反。双荧光素酶报告基因实验证实miR-30d-5p可靶向DBF4,过表达miR-30d-5p可下调DBF4的表达。过表达DBF4可促进LUSC的增殖、迁移、侵袭和EMT,而过表达miR-30d-5p可减弱DBF4对癌细胞的促进作用。结论:miR-30d-5p下调DBF4的表达,调控LUSC的发生发展。
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引用次数: 8
Progression of potential etiologies of the chronic kidney disease of unknown etiology in Sri Lanka. 斯里兰卡不明病因慢性肾脏疾病的潜在病因进展
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 Epub Date: 2020-12-26 DOI: 10.1080/26896583.2020.1852012
Ranaa Aqeelah Faleel, Uthpala Apekshani Jayawardena

Chronic kidney disease of unknown etiology (CKDu) is a major health issue in agricultural areas in Sri Lanka. Despite many attempts to identifying causative factors of CKDu, the real cause/s remain/s elusive to date. Understanding the progression of potential etiologies may provide valuable insight into this quest. Literature relevant to CKDu addresses several etiologies, including quality of drinking water in the affected areas including hardness, fluoride, ionicity, agrochemical and heavy metal contaminations, consumption of contaminated food, and the genetic makeup of vulnerable populations. Progression of the etiologies revealed persistent interest in heavy metals of multiple origins: waterborne, foodborne, or soilborne. Secondary factors, such as water hardness, fluoride, and ionicity appear to act synergistically, aggravating the role of heavy metals on the onset, and the progression of CKDu. Demographical factors, such as male sex, over 50 years of age, agriculture-related occupation, and the consumption of contaminated water and food are intricately related with the disease progression while other minor risk factors such as smoking, alcohol consumption, etc. exasperate the disease condition. Since, none of these etiologies are examined adequately, conducting laboratory exposure studies under in-vivo and in-vitro settings to understand their role in CKDu is crucial.

病因不明的慢性肾病(CKDu)是斯里兰卡农业地区的一个主要健康问题。尽管许多人试图确定CKDu的致病因素,但真正的原因至今仍难以捉摸。了解潜在病因的进展可能为这一探索提供有价值的见解。与CKDu相关的文献涉及几种病因,包括受影响地区的饮用水质量,包括硬度、氟化物、离子性、农用化学品和重金属污染、受污染食品的消费以及易感人群的基因构成。病因学的进展揭示了对多重来源重金属的持续关注:水媒、食源性或土媒。次要因素,如水硬度、氟化物和离子性似乎协同作用,加重重金属在CKDu发病和进展中的作用。人口因素,如男性、50岁以上、与农业有关的职业以及饮用受污染的水和食物,与疾病的进展有着复杂的关系,而其他次要的危险因素,如吸烟、饮酒等,则加剧了疾病的病情。由于这些病因都没有得到充分的检查,因此在体内和体外环境下进行实验室暴露研究以了解它们在CKDu中的作用至关重要。
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引用次数: 3
Sentinel species for biomonitoring and biosurveillance of environmental heavy metals in Nigeria. 尼日利亚环境重金属生物监测和生物监测的哨兵物种。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 Epub Date: 2020-04-27 DOI: 10.1080/26896583.2020.1714370
Cecilia Nwadiuto Amadi, Chiara Frazzoli, Orish Ebere Orisakwe

Nigeria receives copious annual precipitation to nourish its forests and agriculture, it has an extensive river drainage system, and it possesses valuable mineral deposits that stimulate both commercial and artisan mining activities. The combination of these features complicates Nigeria's efforts to produce adequate amounts of healthy foods to support its population. Toxic heavy metals like lead, cadmium, and mercury, and toxic metalloids such as arsenic, are also present in its mineral deposits and they migrate gradually into the soil and water of Nigeria by natural means. However, mining activities can liberate higher levels of toxic metals, which adversely affect Nigerian ecosystems and its food chains. Thus, environmental pollution due to anthropogenic activities is a major public health concern in Nigeria. This review covers the importance of native Nigerian and African wild and cultivated plants along with livestock and wild animals as sentinel species to evaluate heavy metals as environmental stressors and the use of sentinel species for food safety monitoring and for predicting potential risks to human health.

尼日利亚每年都有丰富的降水,滋养着它的森林和农业,它有一个广泛的河流排水系统,它拥有宝贵的矿藏,刺激着商业和手工采矿活动。这些特点的结合使尼日利亚生产足够数量的健康食品以支持其人口的努力复杂化。有毒的重金属,如铅、镉和汞,以及有毒的类金属,如砷,也存在于其矿藏中,并通过自然途径逐渐迁移到尼日利亚的土壤和水中。然而,采矿活动可以释放出更高水平的有毒金属,这对尼日利亚的生态系统及其食物链产生不利影响。因此,人为活动造成的环境污染是尼日利亚一个主要的公共卫生问题。本文综述了尼日利亚和非洲本土野生和栽培植物以及牲畜和野生动物作为前哨物种对评价重金属作为环境压力源的重要性,以及在食品安全监测和预测对人类健康的潜在风险方面使用前哨物种的重要性。
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引用次数: 18
Arsenic and smokeless tobacco exposure induces DNA damage and oxidative stress in reproductive organs of female Swiss albino mice. 砷和无烟烟草暴露可引起雌性瑞士白化小鼠生殖器官的DNA损伤和氧化应激。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 DOI: 10.1080/26896583.2020.1860400
Sweety Nath Barbhuiya, Dharmeswar Barhoi, Anirudha Giri, Sarbani Giri

Arsenic contamination in the groundwater of Southern Assam, India is well-documented. A specific type of smokeless tobacco (sadagura, SG) is highly prevalent among the local population. Thus, the present study is aimed to evaluate the toxicological implications of arsenic and smokeless tobacco co-exposure on the reproductive health of female mice. The estrous cycle of experimental animals was monitored for 30 days. Histopathological studies and comet assay of ovarian and uterine tissues were performed after 30 days of exposure to SG and arsenic (sodium arsenite, SA). Oxidative stress was estimated biochemically by taking tissue glutathione, lipid peroxidation (LPO), and superoxide dismutase activity as endpoints. Our findings indicated a prolonged diestrus phase in the SG + L + SA group (p < 0.001). Histopathological study revealed abnormal tissue architecture in treated groups. Comet assay study showed that SG + SA exposure significantly induced DNA damage in test animals. The elevated LPO level in the SG + SA group indicated oxidative stress generation in the reproductive tissues. The present study suggests that female reproductive organs are vulnerable to SA and SG and oxidative stress generation may be the possible mechanism behind DNA damage, impaired follicular growth, atresia, and altered estrous cycle in the mice test system.

印度阿萨姆邦南部地下水中的砷污染有充分的记录。一种特定类型的无烟烟草(sadagura, SG)在当地人口中非常普遍。因此,本研究旨在评估砷和无烟烟草共同暴露对雌性小鼠生殖健康的毒理学影响。监测实验动物的发情周期30 d。暴露于SG和砷(亚砷酸钠,SA) 30天后,对卵巢和子宫组织进行组织病理学研究和彗星测定。氧化应激以组织谷胱甘肽、脂质过氧化(LPO)和超氧化物歧化酶活性为终点进行生化评估。我们的研究结果表明,SG + L + SA组的死亡期延长(p
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引用次数: 3
Effects of glutathione and cysteine on pyrrolizidine alkaloid-induced hepatotoxicity and DNA adduct formation in rat primary hepatocytes. 谷胱甘肽和半胱氨酸对吡咯利西定生物碱诱导的大鼠原代肝细胞肝毒性和DNA加合物形成的影响。
IF 2.5 4区 环境科学与生态学 Q4 ENVIRONMENTAL SCIENCES Pub Date : 2020-01-01 Epub Date: 2020-04-27 DOI: 10.1080/26896583.2020.1738161
Xiaobo He, Qingsu Xia, Qiang Shi, Peter P Fu

Pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Upon metabolic activation, PAs produce dehydropyrrolizidine alkaloids (dehydro-PAs) as reactive primary pyrrolic metabolites. Dehydro-PAs are unstable, facilely hydrolyzed to (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP). Both dehydro-PAs and DHP are capable of binding to cellular DNA and proteins to form DHP-DNA and DHP-protein adducts leading to tumorigenicity and cytotoxicity. We recently determined that the reaction of dehydro-PAs with glutathione and cysteine generated 7-glutathione-DHP (7-GS-DHP) and 7-cysteine-DHP, respectively which can also bind to DNA to produce DHP-DNA adducts. In this study, we determined the effects of glutathione and cysteine on the induction of hepatocytotoxicity and the formation of DHP-DNA adducts in primary hepatocytes cultured with riddelliine and monocrotaline. We found that both glutathione and cysteine can drastically reduce hepatotoxicity while the levels of DHP-DNA adduct formation are slightly affected.

吡咯利西啶生物碱(PAs)是肝毒性、遗传毒性和致癌的植物化学物质。经过代谢激活,PAs产生脱氢吡咯里西啶生物碱(脱氢PAs)作为活性初级吡咯代谢产物。脱氢pas不稳定,容易水解成(±)-6,7-二氢-7-羟基-1-羟甲基- 5h -吡咯利嗪(DHP)。脱氢pas和DHP都能与细胞DNA和蛋白质结合形成DHP-DNA和DHP-蛋白质加合物,导致致瘤性和细胞毒性。我们最近确定脱氢pas与谷胱甘肽和半胱氨酸反应分别产生7-谷胱甘肽- dhp (7-GS-DHP)和7-半胱氨酸- dhp,它们也可以与DNA结合产生DHP-DNA加合物。在本研究中,我们测定了谷胱甘肽和半胱氨酸对riddelliine和monocrotaline培养的原代肝细胞诱导肝细胞毒性和DHP-DNA加合物形成的影响。我们发现谷胱甘肽和半胱氨酸都能显著降低肝毒性,而DHP-DNA加合物的形成水平受到轻微影响。
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引用次数: 10
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