A Perspective on the Toxicity of Low Concentrations of Petroleum-Derived Polycyclic Aromatic Hydrocarbons to Early Life Stages of Herring and Salmon

This article presents a critical review of two groups of studies that reported adverse effects to salmon and herring eggs and fry from exposure to 1 μg/L or less of aqueous total polycyclic aromatic hydrocarbons (TPAH), as weathered oil, and a more toxic aqueous extract of “very weathered oil.” Exposure media were prepared by continuously flowing water up through vertical columns containing gravel oiled at different concentrations of Prudhoe Bay crude oil. Uncontrolled variables associated with the use of the oiled gravel columns included time- and treatment-dependent variations in the PAH concentration and composition in the exposure water, unexplored toxicity from other oil constituents/degradation products, potential toxicity from bacterial and fungal activity, oil droplets as a potential contaminant source, inherent differences between control and exposed embryo populations, and water flow rate differences. Based on a review of the evidence from published project reports, peer-reviewed publications, chemistry data in a public database, and unpublished reports and laboratory records, the reviewed studies did not establish consistent dose (concentration) response or causality and thus do not demonstrate that dissolved PAH alone from the weathered oil resulted in the claimed effects on fish embryos at low μg/L TPAH concentrations. Accordingly, these studies should not be relied on for management decision-making, when assessing the risk of very low–level PAH exposures to early life stages of fish.     

水环境中工程纳米颗粒物的生态毒理学机理及理想模式生物的筛选

随着纳米技术产业的高速发展,大量工程纳米颗粒物(Engineering nano-particles,ENPs)被排放到自然水环境中,因此对其进行生态毒性及环境风险的研究尤为迫切。综述了ENPs在水环境中的毒理学机理及理想模式生物筛选的研究进展。目前的研究表明ENPs的毒性作用机制主要包括两方面:一是影响细胞信号通路,二是氧化应激造成基因表达的变化。此外,光催化活性、细胞表面附着、溶解特性、表面特征、赋存形态、溶剂效应及与其他环境污染物的协同作用也是可能的毒性作用机理。模式生物的筛选与确定在纳米生态毒理学研究中极为重要。鱼类作为水环境中普遍存在的脊椎动物,群落庞大,其具有行为端点敏感性高、且在生物毒性实验中存在明显的量效关系等特征,被认为是研究ENPs生态毒理学最适合的水生模式生物。研究表明针对在ENPs影响下的未成年鱼类的行为特征研究比传统的胚胎发育及致死率研究更为有效。无脊椎动物和浮游植物同样在各种水环境中普遍存在,对环境污染物极为敏感,且对有害物质具有显著的富集放大效应,因此作为模式生物也具有一定的优势。     

Does Aqueous Fullerene Inhibit the Growth of Saccharomyces cerevisiae or Escherichia coli?

Studies reporting on potentially toxic interactions between aqueous fullerene nanoparticles (nC(60)) and microorganisms have been contradictory. When known confounding factors were avoided, growth yields of Saccharomyces cerevisiae and Escherichia coli cultured in the presence and absence of independently prepared lots of underivatized nC(60) were found not to be significantly different.     

Nickel Carcinogenicity in Relation to the Health Risks from Residual Oil Fly Ash

Epidemiological studies of workers in the nickel industry, animal exposure studies, and reports on the potential mechanisms of nickel-induced toxicity and carcinogenicity indicate that only crystalline sulfidic nickel compounds have been clearly established as carcinogenic or potentially carcinogenic in humans. This observation indicates the need to modify and update regulatory approaches for nickel to reflect noncancer toxicity values for some individual nickel species. Analysis of nickel compounds in residual oil fly ash (ROFA) indicates that sulfidic nickel compounds (e.g., nickel subsulfide, nickel sulfide) are not present. Thus, the potential for emission of carcinogenic nickel compounds from residual oil fly ash appears to be low. Preliminary reference concentrations (RfCs) for a number of nickel compounds, based on non-carcinogenic endpoints, are proposed on the basis of the benchmark dose approach in conjunction with NTP data for nickel species.     

Mitochondrial permeability transition pore in Alzheimer's disease: Cyclophilin D and amyloid beta

Amyloid beta (Aβ) plays a critical role in the pathophysiology of Alzheimer's disease. Increasing evidence indicates mitochondria as an important target of Aβ toxicity; however, the effects of Aβ toxicity on mitochondria have not yet been fully elucidated. Recent biochemical studies in vivo and in vitro implicate mitochondrial permeability transition pore (mPTP) formation involvement in Aβ-mediated mitochondrial dysfunction. mPTP formation results in severe mitochondrial dysfunction such as reactive oxygen species (ROS) generation, mitochondrial membrane potential dissipation, intracellular calcium perturbation, decrease in mitochondrial respiration, release of pro-apoptotic factors and eventually cell death. Cyclophilin D (CypD) is one of the more well-known mPTP components and recent findings reveal that Aβ has significant impact on CypD-mediated mPTP formation. In this review, the role of Aβ in the formation of mPTP and the potential of mPTP inhibition as a therapeutic strategy in AD treatment are examined.     

The vascular endothelium as a target of cadmium toxicity

Cadmium (Cd) is an important industrial and environmental pollutant that can produce a wide variety of adverse effects in humans and animals. A growing volume of evidence indicates that the vascular endothelium may be one of the primary targets of Cd toxicity in vivo. Studies over the past 20 years have shown that Cd, at relatively low, sublethal concentrations, can target vascular endothelial cells at a variety of molecular levels, including cell adhesion molecules, metal ion transporters and protein kinase signaling pathways. The purpose of this review is to summarize the results of these recent studies and to discuss the implications of these findings with regard to the mechanisms of Cd toxicity in specific organs including the lung, liver, kidney, testis and heart. In addition the possible roles of the vascular endothelium in mediating the tumor promoting and anticarcinogenic effects of Cd are discussed.     

Role of particle coating in controlling skin damage photoinduced by titania nanoparticles

TiO₂ nanoparticles hazard is associated to their photocatalytic activity causing release of DNA damaging ROS (Reactive Oxygen Species), lipid peroxidation and skin damage. Various coatings have been proposed to minimize photocatalysis, while keeping the potential to block UV radiations. Uncoated and variously coated commercial nano-titania have been classified on the basis of UVB-induced lipoperoxidation of linoleic acid. A selection of the most and the least protective specimens was then examined by ESR (Electron Spin Resonance) to evidence the presence of surface paramagnetic centres and the release of ROS in aqueous suspensions (spin trapping). Paramagnetic centres and ROS were correlated with the extent of lipid peroxidation. When tested on porcine skin (mimicking the human one), titania acted as on linoleic acid. The combined use of lipid peroxidation of simple fatty acids with ESR analysis is here proposed as a possible screening tool for the evaluation of the potential toxicity of nano-titania in sunscreen preparations.     

TiO2 nanoparticles are phototoxic to marine phytoplankton

Nanoparticulate titanium dioxide (TiO(2)) is highly photoactive, and its function as a photocatalyst drives much of the application demand for TiO(2). Because TiO(2) generates reactive oxygen species (ROS) when exposed to ultraviolet radiation (UVR), nanoparticulate TiO(2) has been used in antibacterial coatings and wastewater disinfection, and has been investigated as an anti-cancer agent. Oxidative stress mediated by photoactive TiO(2) is the likely mechanism of its toxicity, and experiments demonstrating cytotoxicity of TiO(2) have used exposure to strong artificial sources of ultraviolet radiation (UVR). In vivo tests of TiO(2) toxicity with aquatic organisms have typically shown low toxicity, and results across studies have been variable. No work has demonstrated that photoactivity causes environmental toxicity of TiO(2) under natural levels of UVR. Here we show that relatively low levels of ultraviolet light, consistent with those found in nature, can induce toxicity of TiO(2) nanoparticles to marine phytoplankton, the most important primary producers on Earth. No effect of TiO(2) on phytoplankton was found in treatments where UV light was blocked. Under low intensity UVR, ROS in seawater increased with increasing nano-TiO(2) concentration. These increases may lead to increased overall oxidative stress in seawater contaminated by TiO(2), and cause decreased resiliency of marine ecosystems. Phototoxicity must be considered when evaluating environmental impacts of nanomaterials, many of which are photoactive.     

Environmental chemical mediated male reproductive toxicity: Drosophila melanogaster as an alternate animal model

Industrialization and indiscriminate use of agrochemicals have increased the human health risk. Recent epidemiological studies raised a concern for male reproduction given their observations of reduced sperm counts and altered semen quality. Interestingly, environmental factors that include various metals, pesticides and their metabolites have been causally linked to such adversities by their presence in the semen at levels that correlate to infertility. The epidemiological observations were further supported by studies in animal models involving various chemicals. Therefore, in this review, we focused on male reproductive toxicity and the adverse effects of different environmental chemicals on male reproduction. However, it is beyond the scope of this review to provide a detailed appraisal of all of the environmental chemicals that have been associated with reproductive toxicity in animals. Here, we provided the evidence for reproductive adversities of some commonly encountered chemicals (pesticides/metals) in the environment. In view of the recent thrust for an alternate to animal models in research, we subsequently discussed the contributions of Drosophila melanogaster as an alternate animal model for quick screening of toxicants for their reproductive toxicity potential. Finally, we emphasized the genetic and molecular tools offered by Drosophila for understanding the mechanisms underlying the male reproductive toxicity.     

Antibacterial Agents in Mediterranean Finfish Farming: A Synopsis of Drug Pharmacokinetics in Important Euryhaline Fish Species and Possible Environmental Implications

The literature pertaining to the use of registered antibacterial agents in Mediterranean finfish farming is reviewed, with an emphasis on the Greek fish-farming industry. This review provides a scientific resource dedicated to the design of future antibacterial dosing regimes in Mediterranean fish farming, where insufficient supporting information is currently available. This paper addresses the paucity in knowledge concerning pharmacokinetics and the efficacy and environmental impact of commonly used antibacterials needed to direct future research and promote good practices in the euryhaline fish farming industry. Several registered antibacterials are currently available for combating bacterial infections, including tetracyclines, (fluoro) quinolones, potentiated sulfa, penicillin and chloramphenicol derivatives. Based on the available data, oxytetracycline (OTC) and quinolone drugs (oxolinic acid – OA and flumequine – FLU) are the most widely used in Mediterranean aquaculture. As a result these drugs have received the most extensive studies, whereas, there is considerable paucity of reliable data on pharmacokinetic and the depletion characteristics of other drugs used, particularly potentiated sulfa, penicillin derivatives and florfenicol. We find there is incomplete data on drug efficacy and minimum inhibitory concentrations (MIC) for common antibacterials used against the major bacterial pathogens of Mediterranean fish species. Furthermore, a considerable lack of data on environmental drug concentrations around Mediterranean fish farms was also identified, highlighting the need for more extensive environmental studies to monitor contamination in environmental components i.e., water and sediment, and in non-target species (flora and fauna). Prudent selection and use of antibacterials can encourage lower dosage applications, enhance treatment efficacy, and help to minimize contamination of the environment. Selection of readily bioavailable drugs which have low environmental persistence, low aquatic toxicity and high antibacterial efficacy is advised, to reduce potential losses to the environment and associated toxic effects on target species and the development of bacterial resistance. Lack of present data made it impossible to provide thorough and accurate guidance on selection and use of antibacterials and approaches for minimizing environmental impacts for the treatment of major euryhaline aquaculture species.     

Iron acquisition by teleost fish

Iron is a vital micronutrient for teleost fish, being an integral component of proteins involved in cellular respiration and oxygen transfer. However, in excess iron is toxic, and fish need to balance uptake to prevent deficiency vs. potential toxicity. This review assesses the current physiological and molecular knowledge of the mechanisms of iron acquisition in the teleost fish. It focuses on freshwater teleost fish when assessing the gill as a possible site for iron acquisition, and includes a summary of geochemical processes that govern aquatic iron bioavailability. It focuses on marine teleost fish for assessing the mechanism of intestinal iron uptake. Physiological evidence indicates that iron preferentially crosses the apical membrane of both the gills and intestine in the ferrous (Fe2+) state. Molecular evidence supports this, demonstrating the presence of homologues in fish to the large Slc 11a family of evolutionary conserved proteins linked to Fe2+ transport. This symporter is probably linked to a reductase, which reduces either ferric (Fe3+) or organic complexed iron to Fe2+ prior to uptake.     

Oxidative stress and metal carcinogenesis

Occupational and environmental exposures to metals are closely associated with an increased risk of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the exact mechanisms of action are still unclear. Accumulating evidence indicates that reactive oxygen species (ROS) generated by metals play important roles in the etiology of degenerative and chronic diseases. This review covers recent advances in (1) metal-induced generation of ROS and the related mechanisms; (2) the relationship between metal-mediated ROS generation and carcinogenesis; and (3) the signaling proteins involved in metal-induced carcinogenesis, especially intracellular reduction-oxidation-sensitive molecules.     

环境污染物对水生生物产生氧化压力的分子生物标志物

为了能够建立一种简单、快速、准确的环境污染监测预警体系,人们进行了广泛的研究,其中有关环境污染物对分子生物标志物的影响已成为研究热点。生物体内的氧自由基和其它活性氧分子（ROS）对组织和细胞成分造成的伤害,称之为氧化压力,环境中的有毒物质能够对生物体产生不同程度的氧化压力。生物体内的强氧化剂或体外因素（如环境污染物）引起的强氧化物与抗氧化防御系统之间的平衡能够用于评估环境压力对生物体产生影响的程度,尤其适合于评估不同种化学物质引起氧化损伤的程度。这些抗氧化防御系统及其对氧化压力的敏感性在环境毒物学研究中占有非常重要的地位,大量研究结果表明：过渡金属、多环芳烃、有机氯和有机磷农药、多氯联苯、二氧芑和其它异型物质都能够对生物体产生氧化压力。这些有毒物质能够引起各种有害影响,如对膜脂、DNA和蛋白产生损伤;改变抗氧化酶的活性等。总结了这种氧化压力的研究进展情况,并讨论了这些分子生物标志物在水生生物中的应用。     

Analysis of the oxido-redox status of plasma proteins. Technology advances for clinical applications

Reactive oxygen species (ROS) are potentially implicated in renal pathology. Direct evidence is available for animal models of glomerulonephritis but the demonstration of ROS implication in human diseases is only circumstantial and requires further experimental support. One problem limiting any evolution is the brief life of ROS (in terms of milliseconds) that makes it difficult their direct detection 'in vivo'. An alternative is to look at the products of oxidation of proteins that remain in blood as a signature of ROS activity. Recent data have shown the presence of oxidation products of albumin (sulfonic (34)Cys albumin) in serum of patients with focal-glomerulosclerosis, that is a primary glomerular diseases causing nephrotic syndrome. Structural studies based on spectroscopy and calorimetry strengthened the relevance of oxidation of the unique free SH groups of (34)Cys for conformation of albumin, in analogy with what already reported for other proteins. In this review, we present new developments on technologies for the detection of the oxido-redox potential of proteins that are based on the concept that oxidation is inversely correlated with their free content of sulphydryl groups. We describe, in particular, two new iodoacetamide-substituted cyanines that have been developed for labelling sulphydryl groups and can be utilized as stable dyes prior mono- and bi-dimensional electrophoresis. Proteins with low binding with iodoacetamide-cyanines may be considered as surrogate biomarkers of ROS activity. Standardization of these techniques and their acquisition in more laboratories would enable clinicians to plan screening studies on ROS in human diseases.     

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.     

A Perspective on the Toxicity of Petrogenic PAHs to Developing Fish Embryos Related to Environmental Chemistry

Numerous studies demonstrate polynuclear aromatic hydrocarbons (PAHs) dissolved from weathered crude oil adversely affect fish embryos at 0.5 to 23 μg/l. This conclusion has been challenged by studies that claim (1) much lower toxicity of weathered aqueous PAHs; (2) direct contact with dispersed oil droplets plays a significant role or is required for toxicity; (3) that uncontrolled factors (oxygen, ammonia, and sulfides) contribute substantively to toxicity; (4) polar compounds produced by microbial metabolism are the major cause of observed toxicity; and (5) that based on equilibrium models and toxic potential, water contaminated with weathered oil cannot be more toxic per unit mass than effluent contaminated with fresh oil. In contrast, several studies demonstrate high toxicity of weathered oil; shifts in PAH composition were consistent with dissolution (not particle ablation), embryos accumulated dissolved PAHs at low concentrations and were damaged, and assumed confounding factors were inconsequential. Consistent with previous empirical observations of mortality and weathering, temporal shifts in PAH composition (oil weathering) indicate that PAHs dissolved in water should (and do) become more toxic per unit mass with weathering because high molecular weight PAHs are more persistent and toxic than the more abundant low molecular weight PAHs in whole oil.     

Role of glutathione in functioning of the system of antioxidant protection in fish (review)

Oxidative stress causes damage to cell components by reactive oxygen species (ROS) originating from the effect of various chemical pollutants, such as heavy metal cations, polyaromatic hydrocarbons, organochlorine and phosphororganic pesticides, polychlorine biphenyls, dioxins, and other xenobiotics. To avoid pathological consequences of interaction between biological molecules and high-reactive ROS, cells have a detoxification mechanism that uses glutathione, a nonprotein thiol. Glutathione is a component of cellular protection against the toxic action of xenobiotics and metal cations. In the last decade, the effect of environmental pollutants on changes in glutathione concentrations in tissues of aquatic organisms has been touched on in a large number of works. This review summarizes data of the up-to-date studies on glutathione variability in fish tissues under the effect of biogenic and industrial xenobiotics.     

Meta-analysis reveals an extreme “decline effect” in the impacts of ocean acidification on fish behavior

Ocean acidification—decreasing oceanic pH resulting from the uptake of excess atmospheric CO₂—has the potential to affect marine life in the future. Among the possible consequences, a series of studies on coral reef fish suggested that the direct effects of acidification on fish behavior may be extreme and have broad ecological ramifications. Recent studies documenting a lack of effect of experimental ocean acidification on fish behavior, however, call this prediction into question. Indeed, the phenomenon of decreasing effect sizes over time is not uncommon and is typically referred to as the “decline effect.” Here, we explore the consistency and robustness of scientific evidence over the past decade regarding direct effects of ocean acidification on fish behavior. Using a systematic review and meta-analysis of 91 studies empirically testing effects of ocean acidification on fish behavior, we provide quantitative evidence that the research to date on this topic is characterized by a decline effect, where large effects in initial studies have all but disappeared in subsequent studies over a decade. The decline effect in this field cannot be explained by 3 likely biological explanations, including increasing proportions of studies examining (1) cold-water species; (2) nonolfactory-associated behaviors; and (3) nonlarval life stages. Furthermore, the vast majority of studies with large effect sizes in this field tend to be characterized by low sample sizes, yet are published in high-impact journals and have a disproportionate influence on the field in terms of citations. We contend that ocean acidification has a negligible direct impact on fish behavior, and we advocate for improved approaches to minimize the potential for a decline effect in future avenues of research.     

Free radicals and senescence

There is a significant body of experimental evidence that a rise in intracellular reactive oxygen species (ROS) contributes to senescence. Here we review experiments where entry into senescence has been evaluated in cells whose intracellular ROS levels have been modulated by growth in either high or low ambient oxygen concentrations, or where the cellular antioxidant status has been perturbed. In addition, we discuss the observations that senescence triggered by oncogene expression also appears to be in part mediated by a rise in ROS levels. Finally, we discuss the emerging evidence that in vivo senescence might also be triggered by a rise in cellular oxidant levels. Although these data tend to support a role for ROS in mediating senescence, significant questions remain as to whether ROS act in a random or specific fashion and what precise oxidant species acts as the potential senescence trigger.     

Prevention of arsenic-induced hepatic apoptosis by concomitant administration of garlic extracts in mice

Garlic is well known as a folk remedy for a variety of ailments since ancient times, however, very few studies are available suggesting its beneficial role against arsenic toxicity pertaining to its ability to eliminate arsenic from the blood and soft tissues and in reversal of arsenic-induced oxidative stress in affected tissues. The present study was planned to investigate the protective efficacy of aqueous garlic extract using two different doses on parameters suggestive of hepatic injury, tissue oxidative stress and mobilization of arsenic. Further, an attempt to understand the mechanism of arsenic in inducing hepatic apoptosis was also studied. Results of the present study suggested that arsenic administration in mice caused generation of reactive oxygen species (ROS) causing apoptosis through mitochondria-mediated pathway. The ROS generation in hepatic tissue reverted to normal values after co-administration of garlic extracts. The study provides significant evidence that garlic extracts contain strong anti-oxidant property which could be beneficial in preventing arsenic-induced toxicity in cells. However, further research is required to determine whether the results from animal studies are applicable to humans before garlic can be recommended as a putative agent against arsenic toxicity.