有毒污染物对生物体的毒性效应与自由基反应

概括介绍了有毒污染物对生物体毒性效应的基本类型、毒性效应研究的热点问题、毒物诱导自由基产生的机制和自由基对机体的损害机制等,最后指出今后应进一步认识和加强研究的几个方面的问题,如新型有毒污染物对生物体的毒性效应及其毒性效应产生的机制、慢性毒性效应有毒污染物的毒性效应、生态毒理学方法诊断和评价复合污染物对生物的遗传毒性效应、生物标记物研究和合理清除自由基等。     

鱼类通过鱼道内水流速度障碍能力的评估方法

鱼类通过鱼道内水流速度障碍能力的量化对鱼道设计有重要理论和实际价值,其基础是鱼类游泳能力的测定.首先对鱼类游泳能力的研究方法进行了概述总结,指出了鱼类游泳能力经典测试方法存在测定流场与自然情况相差较大的不足;分析了关键要素如鱼类行为特征、生理耗能规律及水力特性对鱼类通过水流速度障碍能力的影响;提出了分析鱼类游泳行为和能力与特征流场的关系,探讨鱼类通过水流障碍行为规律和生理疲劳恢复特征,通过研究仿自然流态下的鱼类自由游泳行为、水力计算及生理耗能的关系,构建多因素鱼类游泳能力关系式,定量评价鱼类通过鱼道内水流速度障碍的发展方向.     

丙烯酰胺神经系统毒性机制

丙烯酰胺(acrylamide,ACR)是公认的神经、致癌、遗传和雄性生殖毒物。高温(120 oC)烹饪富含淀粉食物会产生ACR及致癌性已在近年引起世界卫生组织(WHO)和联合国粮农组织(FAO)的关注,本文就ACR的性质、危害、代谢、对神经行为的影响和神经毒性机制的研究状况方面进行综述,以期为ACR对神经系统毒性作用的特点、机制及危险度评定和防治提供科学依据。     

哺乳动物母体环境程序化后代表型和神经发育可塑性的研究进展

繁殖期环境程序化后代生理和行为等适合度特征、神经系统的发育可塑性是生理和行为调节的关键机制。概述了繁殖期环境对野生小型哺乳动物代谢生理、行为和神经可塑性的影响。早期环境对野生动物生理和行为表型及神经再生的长期影响正越来越受到生物学家的关注,对于解释野外不同季节出生的后代具有不同生活史特征的神经机制具有重要意义。     

大脑皮层发育及神经前体细胞

哺乳动物的大脑皮层是神经系统中最复杂的结构。现代医学对许多神经系统疾病往往束手无策。了解脑发育的过程和机制对认识神经系统如何正常行使功能,以及神经系统疾病的发生、发展、治疗具有重要意义。神经发育生物学的关键问题之一,即数量巨大的神经细胞如何从相对有限的神经前体细胞中有序产生。简要介绍了大脑皮层的发育过程及参与神经发生的各类神经前体细胞。     

鸟类鸣啭学习神经回路的发育可塑性

鸟类鸣啭控制系统已成为人们研究神经系统与学习、行为和发育关系的重要模型。鸣啭系统在发育中所表现出的神经和行为明显变化的特点,为我们理解语言学习敏感期、突触联系的再分布、结构特化以及细胞死亡与神经发生提供了宝贵的信息。在许多方面,鸣禽鸟啭系统都有别于哺乳动物,这为特定理论问题的研究提供了新的途径。     

Sigma-1 受体的药理学作用及相关药物研究进展

常见的神经系统疾病如药物成瘾及其导致的神经毒性、神经精神疾病、神经退行性疾病等,严重影响人类健康与正常生活。而临 床上现有的相关治疗药物往往会导致锥体外系反应等副作用,且用药后治疗不够彻底,疾病易复发,因此,开发新靶点及新型有效、安 全的相关治疗药物,迫在眉睫。Sigma-1 受体是一种受体型分子伴侣,参与多种神经传导系统的调节,可与多种精神类药物结合,有望 成为神经系统调节药物的重要靶点。研究发现,有些小分子配体对 Sigma-1 受体具有良好的亲和力,在药物成瘾、精神分裂症、抑郁症、 阿尔茨海默病等疾病中显示出较好疗效。对 Sigma-1 受体的药理学作用以及相关小分子配体药物的研发作一综述。     

神经活性甾体激素的快速中枢效应

过去认为甾体激素只能由神经系统外的内分泌组织产生。甾体激素的作用原理为经典的基因作用机制。近年来的研究发现脑组织也能产生神经源性的神经甾体激素,而且神经细胞膜表面存在甾体激素结合位点。神经活性甾体激素和脑源性神经甾体激素可通过调制配基门控离子通道受体、Ｇ蛋白耦联受体产生快速中枢效应。     

土壤污染生态毒性效应评价研究进展

随着社会经济的高度发展,人类活动加剧,我国土壤污染问题突出,不仅威胁人体健康,同时也严重威胁动植物及微生物的安全,生态安全问题不容忽视。但是我国土壤污染风险管控目前主要关注人体健康,对生态系统的关注较少,缺乏土壤污染生态风险评估技术指南及基于生态风险的土壤环境质量基准及标准。准确评价土壤污染生态毒性效应,是制定土壤环境质量标准、实现生态风险评估及预警与管控的重要基础。针对土壤污染生态毒性效应评价问题,分别对土壤污染生态毒性效应特征、评价方法、评价终点、暴露-效应关系构建、生态毒性效应外推,以及群落水平与复合污染生态毒性效应评价等方面的关键问题展开了讨论,指出目前土壤污染生态毒性效应评价主要是基于单物种的急性毒性测试,利用个体和亚个体水平的指示物作为评价终点,缺乏针对群落及生态系统高水平评价终点的生态毒性效应评价方法,定量评价污染物尤其是复合污染物对土壤生物群落及生态系统的影响,是土壤污染生态毒性效应评价的关键问题和难点问题。建议今后重点开展以下3方面的工作1)群落及生态系统水平评价终点的筛选;2)土壤污染生态毒性效应环境影响因子识别及影响机制研究;3)土壤复合污染联合毒性效应定量评价及...     

神经退行性疾病的表观遗传学

研究发现多种疾病的发生与表观遗传学相关.有证据显示表观遗传学信号在大脑中起着重要调节作用,在哺乳动物中枢神经系统中DNA甲基化动力学被发现是表观遗传学调节的主要组成,染色质修饰药物的快速发展显示出对神经系统中范围广泛的退行性功能紊乱出人意料的治疗作用,促进了人们对神经退行性疾病的表观遗传学机制研究.其中,研究得比较多的是DNA甲基化、组蛋白修饰及染色质重塑.这些研究为神经退行性疾病的治疗提供了潜在靶点,并为开发相关药物提供了线索.对疾病表观遗传学机制及药物的作用机制的进一步研究将为疾病治疗提供更多靶点,为神经退行性疾病提供确切的有效治疗途径,具有积极意义.     

Zebrafish model systems for developmental neurobehavioral toxicology

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models. Birth Defects Research (Part C) 99:14–23, 2013. © 2013 Wiley Periodicals, Inc.     

Perspective on Ecotoxicology of PAHs to Fish

This article provides a perspective on recent research on the effects of PAHs on fish. Fish are visible members of aquatic communities that are vulnerable to PAH contamination. The ecotoxicology of fish and PAHs can be complex. Fish are a diverse group that can have complicated life cycles and behavior and can be exposed to PAH-contaminated sediments and water by a variety of routes, including respiration; ingestion of food, sediment, and detritus; and dermal absorption. PAHs are a complex group of chemicals with similar chemical structure but a variety of chemical and physical attributes and are usually produced and occur in the environment as mixtures. Individual PAHs may elicit a variety of effects in different fish species, and different PAHs may elicit different effects in any single fish species. The variation in both fish and PAHs is reflected in the wide range of adverse effects observed in fish exposed to PAHs. Some observed effects include narcosis, mortality in all life stages, decrease in growth, lower condition factor, edema, cardiac dysfunction, a variety of deformities, lesions and tumors of the skin and liver, cataracts, damage to immune systems and compromised immunity, estrogenic effects, bioaccumulation, bioconcentration, trophic transfer, and biochemical changes, some of which can be used as biomarkers.     

Single and combined effects of microplastics and pyrene on juveniles (0+ group) of the common goby Pomatoschistus microps (Teleostei,Gobiidae)

Microplastic particles have increasingly been detected in aquatic biota, from zooplankton to fish, raising concern for potential effects on aquatic organisms. In addition, they may potentially influence the toxicity of other contaminants in the marine environment. The aim of this study was to clarify whether polyethylene microspheres (1–5 μm) modulate short-term toxicity of the polycyclic aromatic hydrocarbon pyrene to juveniles (0+ group) of the common goby (Pomatoschistus microps). Fish were exposed for 96 h to pyrene (20 and 200 μg L⁻¹) in the absence and presence of microplastics (0, 18.4 and 184 μg L⁻¹). Mortality, bile pyrene metabolites, and biomarkers involved in neurotransmission, aerobic energy production, biotransformation and oxidative stress were quantified. Microplastics delayed pyrene-induced fish mortality and increased the concentration of bile pyrene metabolites. Microplastics, alone or in combination with pyrene, significantly reduced acetylcholinesterase (AChE) activity, an effect also observed for pyrene alone. The mixture also decreased isocitrate dehydrogenase (IDH) activity. No significant effects were found for glutathione S-transferase activity or lipid peroxidation. Overall, results show that: (i) microplastics modulate either the bioavailability or biotransformation of pyrene; (ii) simultaneous exposure to microplastics and pyrene decrease the energy available through the aerobic pathway of energy production; and (iii) microplastics inhibit AChE activity. The mechanism for AChE inhibition appeared to be different for pyrene and microplastics, since simultaneous exposure to both did not increase significantly the inhibitory effect. The observed neurotoxic effects of microplastics per se and the effects on IDH activity of the two stressors combined are of concern because they may increase mortality in natural fish populations. More studies need to be carried out on possible combined effects of microplastics and polycyclic aromatic hydrocarbons on fish, particularly juveniles.     

Methylmercury and brain development: A review of recent literature

Methylmercury (MeHg) is a potent environmental pollutant, which elicits significant toxicity in humans. The central nervous system (CNS) is the primary target of toxicity, and is particularly vulnerable during development. Maternal exposure to MeHg via consumption of fish and seafood can have irreversible effects on the neurobehavioral development of children, even in the absence of symptoms in the mother. It is well documented that developmental MeHg exposure may lead to neurological alterations, including cognitive and motor dysfunction. The neurotoxic effects of MeHg on the developing brain have been extensively studied. The mechanism of toxicity, however, is not fully understood. No single process can explain the multitude of effects observed in MeHg-induced neurotoxicity. This review summarizes the most current knowledge on the effects of MeHg during nervous system development considering both, in vitro and in vivo experimental models. Considerable attention was directed towards the role of glutamate and calcium dyshomeostasis, mitochondrial dysfunction, as well as the effects of MeHg on cytoskeletal components/regulators.     

Plenty more fish in the sea: comparative and functional genomics using teleost models.

Biology has collaborated with evolution to create an enormous repertoire of animal variation. This in turn has provided experimental biologists with models that can be used in the lab to simulate more complex systems. Amongst the organisms that have been used in this way are fish, where a large number of species have been utilised in a variety of different ways. Fish possess the smallest genomes of any vertebrate, making them ideal as models for genome analysis and gene discovery. Fish are also easy to maintain in a laboratory environment and can be bred easily. Fish often have well-defined physiology and respond well to many experimental procedures. Finally, fish are of great economic importance in their own right, as one of the world's largest sources of protein. In this review, the relationship between fish species is examined along with the role of different fish models in a wide range of biological disciplines.     

Cytotoxicity assays with fish cells as an alternative to the acute lethality test with fish

In ecotoxicology, in vitro assays with fish cells are currently applied for mechanistic studies, bioanalytical purposes and toxicity screening. This paper discusses the potential of cytotoxicity assays with fish cells to reduce, refine or replace acute lethality tests using fish. Basal cytotoxicity data obtained with fish cell lines or fish primary cell cultures show a reasonable to good correlation with lethality data from acute toxicity tests, with the exception of compounds that exert a specific mode of toxic action. Basal cytotoxicity data from fish cell lines also correlate well with cytotoxicity data from mammalian cell lines. However, both the piscine and mammalian in vitro assays are clearly less sensitive than the fish test. Therefore, in vivo LC50 values (concentrations of the test compounds that are lethal to 50% of the fish in the experiment within 96 hours) currently cannot be predicted from in vitro values. This in vitro-in vivo difference in sensitivity appears to be true for both fish cell lines and mammalian cell lines. Given the good in vitro-in vivo correlation in toxicity ranking, together with the clear-cut difference in sensitivity, the role of cytotoxicity assays in a tiered alternative testing strategy could be in priority setting in relation to toxic hazard and in the toxicity classification of chemicals and environmental samples.     

Structural and functional effects of heavy metals on the nervous system, including sense organs, of fish.

1. Today, fish in the environment are inevitably exposed to chemical pollution. Although most hazardous substances are present at concentrations far below the lethal level, they may still cause serious damage to the life processes of these animals. 2. Fish depend on an intact nervous system, including their sense organs, for mediating relevant behaviour such as food search, predator recognition, communication and orientation. 3. Unfortunately, the nervous system is most vulnerable and injuries to its elements may dramatically change the behaviour and consequently the survival of fish. 4. Heavy metals are well known pollutants in the aquatic environment. Their interaction with relevant chemical stimuli may interfere with the communication between fish and environment. 5. The affinity for a number of ligands and macromolecules makes heavy metals most potent neurotoxins. 6. The present Mini-Review highlights some aspects of how trace concentrations of mercury, copper and lead affect the integrity of the fish nervous system; structurally, physiologically and biochemically.     

Identification of toxic fatty acid amides isolated from the harmful alga Prymnesium parvum carter

The golden alga Prymnesium parvum has been implicated in fish and aquatic animal kills globally for over a century. In addition to widespread ecological impacts through the loss of entire fish populations within lakes, an economic burden is also felt by state and local agencies due to year class losses of fish raised for stocking lakes as well as loss of fishing and recreational use of the affected water. Multiple compounds have been implicated in P. parvum toxicity, but the unequivocal identification and characterization of all P. parvum toxins remained to be accomplished. To unambiguously characterize these toxins, we analyzed laboratory-cultured cells exposed to limited nitrogen and phosphorus concentrations, uni-algal wild cells collected from an ichthytoxic bloom event at Lake Wichita, TX, and the water from both cultured and field-collected algae. A bioassay-guided fractionation process was employed to chemically isolate P. parvum toxins using both mammalian cells and larval fish. The results of these assays revealed that there was a distinct similarity in the toxic compounds characterized as seven primary fatty acid amides (myristamide, palmitamide, linoleamide, oleamide, elaidamide, stearamide, and erucamide) and one hydroxamic acid (linoleyl hydroxamic acid). These compounds display cytotoxic and ichthytoxic activity and have not yet been reported in P. parvum toxicity or in the toxicity of harmful algal species.     

Metal pollution-induced immunomodulation in fish

The exact relationship between disease incidence in aquatic organisms and environmental pollution is not well defined. A number of mechanisms by which aquatic pollutants may act to increase disease incidence in fish have been speculated, many suggesting immunosuppression as a link in the etiology of disease among fishes in highly contaminated areas. This article will review the effects of metal pollutants on the immune responses of fish by examining in vitro and in vivo laboratory studies carried out since 1980. It will also describe how those alterations may be responsible for pollution-associated diseases in directly exposed fish. While a large number of environmental contaminants represent aquatic pollutants of concern (e.g. polycyclic aromatic hydrocarbons, chlorinated organics, and pesticides), heavy metals were selected as the pollutants for this review because of their: (a) prevalence in polluted aquatic environments; (b) immunotoxic potential in mammalian systems; (c) ability to induce tumors in exposed rodents; and (d) their overall toxicity in a variety of species. It can be concluded that a number of heavy metal pollutants shown to be immunotoxic in mammalian systems, including cadmium, chromium, copper, lead, manganese, nickel, and zic, also alter immunoregulatory functions in a variety of fish species. These alterations may ultimately lead to increased host susceptibility to infectious and malignant diseases in fish inhabiting heavy metal-contaminated waters.     

Evolution of sialic acid-binding proteins: molecular cloning and expression of fish siglec-4

Siglecs are the largest family of sialic acid-recognizing lectins identified so far with 11 members in the human genome. Most of these siglecs are exclusively expressed by cells of the immune system. Comparison of different mammalian species has revealed differential and complex evolutionary paths for this protein family, even within the primate lineage. To understand the evolution of siglecs, in particular the origin of this family, we investigated the occurrence of corresponding genes in bony fish. Interestingly, only unambiguous orthologs of mammalian siglec-4, a cell adhesion molecule expressed exclusively in the nervous system, could be identified in the genomes of fugu and zebrafish, whereas no obvious orthologs of the other mammalian siglecs were found. As in mammals, fish siglec-4 expression is restricted to nervous tissues as demonstrated by northern blot. Expressed as recombinant protein, fish siglec-4 binds to sialic acids with a specificity similar to the mammalian orthologs. Relatively low sequence similarities in the cytoplasmic tail as well as an additional splice variant found in fish siglec-4 suggest alternative signaling pathways compared to mammalian species. Our observations suggest that this siglec occurs at least in the nervous system of all vertebrates.