环境污染物导致氧化应激的关键信号通路及其检测方法

环境污染物能够以多种途径进入生物体内,在体内产生含氧自由基等活性氧物质,并通过多种信号通路及酶反应引起氧化应激,造成生物体内的脂质过氧化、蛋白质损伤、DNA表达改变、酶失活等,从而引发心血管疾病、风湿类疾病、感染及癌症等的发生。本文对环境污染物致氧化应激产生的原因、涉及的信号通路及酶反应、造成的危害,以及常见的基于细胞模型的氧化应激检测方法进行了综述,期望为评价环境污染物和检测氧化损伤提供参考。     

环境污染物对精子损伤机制的研究进展

越来越多的研究表明,环境污染是多种生物生殖力下降的主要原因之一,而精子作为雄性生物的生殖细胞,因高度分化丧失了自我修复能力,极易受环境因素的胁迫。但环境污染物致生物体精子损伤机制的研究目前尚缺乏完整、系统的体系。本文在总结近年来国内外相关研究的基础上,从环境污染物诱导精子产生氧化应激、改变生精细胞的细胞周期、诱导正常生精细胞发生细胞凋亡和扰乱生物体雄激素水平4个方面综合探讨了环境污染物损害精子形态结构、功能以及降低精子数量的潜在作用模式,为开发精子损伤的早期特异性分子标记物奠定了理论基础,同时也为污染物致精子损伤的机制研究提供新的思路。     

石墨烯纳米材料对哺乳动物的毒性及其作用机制

石墨烯是一种应用广泛的新兴非金属纳米材料，具有独特的电学机械性能、超大的比表面积以及潜在的生物相容性，在材料、电子、能源、光学以及生物医学等领域得到广泛应用。与此同时，石墨烯的环境行为和生物毒性也随之引起日益广泛的关注。本文通过对石墨烯纳米材料的动物毒性、细胞毒性、毒性影响因素和毒性机制等相关研究进展进行总结。石墨烯纳米材料可通过气管滴注、吸入、静脉注射、腹腔注射以及口服等方式进入体内，通过机械屏障、血脑屏障和血液胎盘屏障等积累在肺、肝、脾等部位引起急性或者慢性损伤；目前有关石墨烯毒性机制的研究主要集中于线粒体损伤、DNA损伤、炎性反应、凋亡等终点及氧化应激参与的复杂信号通路，不同石墨烯纳米材料的浓度、尺寸、表面结构和官能团等对石墨烯的生物毒性影响不同。鉴于当前该领域研究的局限性，对石墨烯纳米材料生物毒性研究的发展方向进行了展望，进而为石墨烯材料的安全应用提供理论借鉴和实践参考。     

生物扰动对沉积物中污染物环境行为与生物可利用性的影响

疏水性有机污染物进入环境水体后易于与沉积物结合，对沉积物中的底栖动物造成危害。底栖动物引起的生物扰动作用可以通过改变沉积物的地球化学性质，对其中污染物的赋存形态、迁移转化和生物可利用性产生重要影响。在综述了国内外生物扰动影响沉积物中污染物环境行为和生物可利用性的最新研究进展基础上，重点讨论了沉积物颗粒交换、水体环境条件改变、疏水有机污染物解吸释放过程以及对生物扰动影响的定量化表征。最后对该研究方向进行了展望，指出应重点研究多种污染物及不同生物共存条件下的生态效应，以及造成沉积物扰动的影响因素的定量化表征等。     

石墨烯纳米材料对哺乳动物的毒性及其作用机制

石墨烯是一种新兴纳米材料,具有独特的电学和光学性质、超大的比表面积以及潜在的生物相容性,在材料和电子产业、能源、环境以及生物医学等领域得到广泛应用。与此同时,石墨烯的环境行为和生物毒性也随之引起日益广泛的关注。本文通过对石墨烯纳米材料的生物毒性、细胞毒性、毒性影响因素和毒性机制等相关研究进展进行总结。石墨烯纳米材料可通过气管滴注、吸入、静脉注射、腹腔注射以及口服等方式进入体内,通过机械屏障、血脑屏障和血液胎盘屏障等积累在肺、肝、脾等部位引起急性或者慢性损伤;目前有关石墨烯毒性机制的研究主要集中于线粒体损伤、DNA损伤、炎性反应、凋亡等终点及氧化应激参与的复杂信号通路,不同石墨烯纳米材料的浓度、尺寸、表面结构和官能团等对石墨烯的生物毒性影响不同。鉴于当前该领域研究的局限性,对石墨烯纳米材料生物毒性研究的发展方向进行了展望,进而为石墨烯材料的安全应用提供理论借鉴和实践参考。     

苯乙烯致DNA间接损伤效应的光电化学生物传感器快速检测

许多有机化合物自身没有致癌毒性,但进入生物体内,经过体内代谢酶的催化后转化成活性中间体,与DNA形成共价化合物.这些间接的损伤会最终导致DNA分子结构和功能的变化,对人类的健康造成威胁.因此,建立一种快速有效的方法检测间接致癌化合物对DNA的损伤,成为当前研究的热点.论文建立了一种新型的光电化学生物传感器来检测有机化合物苯乙烯对DNA的间接损伤效应,该传感器以层层自组装的方式将光电信号分子、双链DNA和血红蛋白组装在半导体电极上.在H2O2存在的条件下,传感膜中的血红蛋白可将苯乙烯转化为氧化苯乙烯,氧化苯乙烯扩散到膜内,与DNA形成加合物,引起DNA结构变化,导致光电分子光电流信号的增加.实验中,将修饰好的电极置于终浓度为2mM H2O2和2%苯乙烯(体积比)的混合液(pH7.3的磷酸缓冲液配制)中反应一段时间后,在电解质溶液中进行光电流检测.实验结果表明,光电流信号随着反应时间逐渐升高,在30min后趋于稳定,表明苯乙烯在传感膜上的氧化和DNA的损伤反应基本完成.与反应前相比,反应后光电流增加了40%,并且酶催化苯乙烯生成的氧化苯乙烯经紫外可见光谱得到验证.论文建立的光电化学生物传感器模拟了体内DNA损伤反应过程,能快速有效地检测苯乙烯对DNA的间接损伤效应,有望为有机化合物潜在基因毒性的风险评估提供一个快速筛查工具。     

环境污染条件下生物体内DNA损伤的生物标记物研究进展

在正常条件下生物体内的基因组是稳定的;但在环境污染条件下,其DNA容易遭受伤害,主要损伤形式为:碱基改变、脱碱基位点、碱基错配、插入或缺失片段、嘧啶联合、DNA加合物、DNA链断裂、甲基化损伤、DNA链内和链间交联等. 这些受损的DNA对生物细胞产生遗传毒性或细胞毒性. 利用生物标记物进行DNA损伤的检测和定量分析是可行的方法. 本文重点介绍了一些典型的DNA损伤(如DNA加合物、断裂、DNA序列改变等)的生物标记物及其检测方法;认为这些生物标记物在环境污染物的早期诊断和评价方面具有广阔的应用前景. 参32     

Impact of environmental pollutants on vertebrate thyroid systems

甲状腺激素在脊椎动物新陈代谢、生长发育与繁殖等生理过程中起着重要的调节作用.环境污染物种类和数量不断增加,其中有很多污染物具有环境内分泌干扰的作用.甲状腺对环境污染物具有极敏感的反应,污染物不仅会引起滤泡及滤泡细胞大小、滤泡细胞数量和滤泡腔中胶质含量的改变,影响到甲状腺激素合成、分泌、转运以及代谢中多种酶的表达和活性变化,还参与和甲状腺激素的竞争性结合,进而影响到机体中由甲状腺激素调节的各项生理功能,甚至会导致机体趋于死亡.由于两栖类幼体——蝌蚪的变态发育阶段直接受到甲状腺激素的调控,现已被确认为筛选和研究环境内分泌干扰物的首选生物检测指示动物.     

脂质组学在环境领域中的应用

脂质是生物体内重要的组成物质之一,具有多种重要的生物学功能。脂质组学作为代谢组学的一个重要分支,主要通过研究生物体内脂质化合物及脂质代谢谱的变化,进而鉴定生物标志物,分析相关代谢通路,阐明生物体响应外界刺激的机制。随着分析技术的不断进步,尤其是色谱和质谱技术的引入,极大地推动了脂质组学研究的发展,并扩展了其应用范围。本文介绍了脂质组学的研究方法及其在环境领域中的应用前景,重点讨论了脂质组学及多组学联用技术在环境胁迫耐受性及环境污染物毒性评价中的应用。     

金属纳米颗粒的环境行为及其与藻类的相互作用概述

金属纳米颗粒在各领域的应用日益广泛，可通过多种途径进入环境，并在水生生态系统中积累.因此关于其进入水环境后的行为及与水中初级生产者—藻类相互作用的研究至关重要.金属纳米颗粒在水中会发生团聚、沉降、溶解、硫化反应及光化学反应等，这些行为受到自身理化性质(大小、形状、表面电荷、晶体结构、化学组成等)和环境因素(pH、离子强度、阳离子价态等)的影响，进而改变金属纳米颗粒在藻类表面的吸附聚集和可能的吸收累积.金属纳米颗粒还可能影响藻类光合作用、引起氧化应激、甚至造成藻类的凋亡.同时，与金属纳米颗粒共存的其它污染物及天然有机质也可能改变金属纳米颗粒的行为、生物吸附、生物累积和生物效应.相应地，藻类在面对金属纳米颗粒胁迫时也会启动自我防御机制.尽管如此，真实环境中金属纳米颗粒与藻类的相互作用及分子机制仍有待进一步研究.     

过敏症状儿童室内PM_(2.5)对小鼠巨噬细胞的氧化损伤及VE的抗氧化保护作用研究

越来越多的研究提示,主要空气污染物PM_(2.5)暴露浓度的升高与儿童过敏性疾病的发病率有着密切的关系,然而PM_(2.5)暴露与过敏性疾病之间的关联尚未完全阐明。为探究患有过敏症状儿童的室内PM_(2.5)对小鼠巨噬细胞的氧化损伤作用以及维生素E(vitamin E,VE)的抗氧化保护作用,从5户患有1种或1种以上的过敏性症状(如过敏性鼻炎、哮喘)儿童的室内采集PM_(2.5),分别考察了不同剂量PM_(2.5)暴露24 h后如何影响小鼠巨噬细胞的氧化应激水平,指标包括活性氧(ROS),还原型谷胱甘肽(GSH),丙二醛(MDA),8-羟基脱氧鸟苷(8-OH-dG),以及炎症因子水平,指标包括肿瘤坏死因子ɑ(TNF-ɑ),白介素8β(IL-8β)的影响。结果表明,200μg·mL~(-1)PM_(2.5)暴露组与对照组比较,细胞内ROS积累,出现脂质过氧化以及DNA损伤,并伴有炎症反应的发生,差异均有统计学意义(P0.05或P0.01);VE(50 mg·mL~(-1))+200μg·mL~(-1)PM_(2.5)组的ROS、MDA、8-OHdG、TNF-ɑ、IL-8β含量低于200μg·mL~(-1)PM_(2.5)组,GSH含量高于200μg·mL~(-1)PM_(2.5)组。较高剂量(200μg·mL~(-1))PM_(2.5)可诱导小鼠腹腔巨噬细胞出现氧化损伤,VE在该应激过程中起着一定的保护作用。     

Microbial metabolism of chlorobiphenyls

Photochemical reactions induced by sunlight contribute to the overall chemistry of natural water systems in many ways. The degradation of pollutants, dissolution of iron and manganese sediments, cycling of trace metal nutrients, and reactions of aquatic nitrogen and oxygen species are some of the many processes having solar photolysis pathways. This paper reviews recent research concerned with photo‐decomposition of pollutants, photolysis of nitrite and nitrate, photosensitization by humic materials and the generation of reactive intermediates. In addition, background material is presented concerning the basic principles of photochemistry and the limited wavelength range of effective solar radiation.     

Involvement of mitochondrial-mediated caspase-3 activation and lysosomal labilization in acrylamide-induced liver toxicity

Acrylamide (ACR) is a chemical frequently used in both industrial and synthetic processes and may be produced during food processing. ACR at very high concentrations is postulated to exert its toxicity through the stimulation of an oxidative stress. ACR in excessive doses induces the central nervous system, reproduction, and genetic toxicity. However, ACR effects on the liver, a major organ of drug metabolism, have not been adequately explored. In addition, the role of mitochondria in an ACR-mediated hepatotoxicity is still unclear. The aim of this study was to investigate the cytotoxic mechanisms attributed to ACR using isolated rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method and incubated with an EC50_2hr concentration of ACR for 3 hr. The EC50_{2 hr} of ACR on isolated rat hepatocytes was determined to be 1 mM. Based on our results, hepatocytes cytotoxicity of ACR (1 mM) was mediated by a reactive oxygen species formation and lipid peroxidation. Incubation of hepatocytes with ACR produced rapid hepatocyte glutathione depletion which is another marker of the cellular oxidative stress. ACR cytotoxicity was also associated with mitochondrial injury as evidenced by the decline of mitochondrial membrane potential and lysosomal membrane leakiness. Our results also showed that ACR induced caspase-3 activation, the final mediator of apoptosis signaling. These findings contribute to a better understanding underlying mechanisms involved in ACR hepatotoxicity originating from the oxidative stress and ending in mitochondrial/lysosomal damage and cell death signaling.     

Toxicity of depleted uranium on isolated liver mitochondria: a revised mechanistic vision for justification of clinical complication of depleted uranium (DU) on liver

Depleted uranium (DU) is widely used in military anti-armor weapons. Recent evidence suggested that oxidative stress and mitochondrial dysfunction may contribute to DU-induced toxicity. However, the underlying mechanisms of DU toxicity in mitochondria are not well understood. In this study, liver mitochondria were obtained from Wistar rats treated with DU in the form of uranyl acetate (UA) (0.5, 1 or 2 mg/kg i.p.) using differential centrifugation. For in vitro experiments, control rat liver mitochondria were incubated with different concentrations of UA (50, 100 or 200 μM) for 1 hr. Mitochondrial reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential, and mitochondrial swelling were examined by flow cytometry. Mitochondrial sources of ROS formation were determined using specific substrates and inhibitors. Extent of lipid peroxidation (LPO) and glutathione (GSH) oxidation, and also complex II and IV activities were detected via spectroscopy. Further, the concentration of ATP and ATP/ADP ratio was measured using luciferase enzyme and release of cytochrome c from mitochondria which was detected by ELISA kit. UA induced succinate-supported mitochondrial ROS production, elevated LPO levels, GSH oxidation, and mitochondrial complex II inhibition. UA also induced mitochondrial permeability transition and increase in cytochrome c release which subsequently disturbed oxidative phosphorylation and reduced the mitochondrial ATP concentration. Data suggest that mitochondrial oxidative stress and uncoupling of oxidative phosphorylation may play key roles in DU-induced hepatic toxicity.     

Salicylic acid to decrease plant stress

Pollution and climate change degrade plant health. Plant stress can be decreased by application of salicylic acid, an hormone involved in plant signaling. Salicylic acid indeed initiates pathogenesis-related gene expression and synthesis of defensive compounds involved in local resistance and systemic acquired resistance. Salicylic acid may thus be used against pathogen virulence, heavy metal stresses, salt stress, and toxicities of other elements. Applied salicylic acid improves photosynthesis, growth, and various other physiological and biochemical characteristics in stressed plants. Salicylic acid antagonizes the oxidative damaging effect of metal toxicity directly by acting as an antioxidant to scavenge the reactive oxygen species and by activating the antioxidant systems of plants and indirectly by reducing uptake of metals from their medium of growth. We review here the use of exogenous salicylic acid in alleviating bacterial, fungal, and viral diseases, heavy metal toxicity, toxicity of essential micronutrients, and salt stress.     

Antioxidant enzymatic activities and lipid peroxidation in liver and ovary of zebrafish (Danio rerio) exposed to deltamethrin

Deltamethrin (DM) is being used as a substitute for organochlorines and organophosphates in pest control because of its low environmental persistence and toxicity. But it has become an environmental contaminant as it has been used widely. In this study, we investigated the effect of DM (technical grade) on the antioxidant system of adult zebrafish. For this, six-month-old fish were exposed to 2, 4 and 6?μg/L of DM for 96?h. The tissues selected were liver and ovary. Our data showed that exposure to DM increases CAT (catalase), SOD (superoxide dismutase), GPx (glutathione peroxidase, antioxidant enzymes), LPO (lipid peroxidation, non-enzymatic antioxidant) and GST (glutathione S-transferase, detoxifying enzyme) in liver and ovary. Increased GST could detoxify the toxicant; still there could be enough DM to cause oxidative stress. It appears from our study that zebrafish used compensatory mechanisms in eliminating reactive oxygen species. These data will be useful as oxidative stress is being used as a biomarker for aquatic pollution.     

Genotoxicity in the freshwater gastropod Lymnaea luteola L: assessment of cell type sensitivities to lead nitrate

The aquatic ecosystems are converting into the highly contaminated site due to environmental pollutants. The present study explores the oxidative stress and toxic potential of lead nitrate in freshwater snail Lymnaea luteola (L. luteola) L. The snails were exposed to an environmentally relevant concentration of lead nitrate for 24 and 96?h. Later exposure to lead nitrate (0, 10, 20 and 40?µg/mL) to the freshwater snail, the level of reactive oxygen species, malondialdehyde and nitric oxide (NO) were increased and glutathione, glutathione-S-transferase were decreased. Lead-nitrate-induced haemocyte cell death and it was observed by using Annexin-V FITC/PI through a flow cytometer. DNA damage in haemocyte cells was measured at above doses of lead-nitrate exposure for 24 and 96?h and it was compared to the untreated snail. Average tail DNA (%) and olive tail moment in single-cell gel test were increased dose and duration fashion and maximum DNA damage was measured at 96?h. These results indicate the potential toxicity and genotoxicity of lead nitrate in acute treatment to L. luteola and single-cell gel test are the assay for rapid detection of genetic effects.