Macrophage activity and histopathology of the lymphohematopoietic organs in male Wistar rats orally exposed to single or mixed pesticides

The noxious effects of low or effective dose exposure to single or mixed pesticides on macrophage activity and the lymphohematopoietic organs were investigated. Male Wistar rats were orally exposed to dichlorvos, dicofol, endosulfan, dieldrin and permethrin, either as single or combined mixtures during a 28-day study containing eight groups: one group received a semipurified diet (non-treated); two groups received a semipurified diet containing low dose mixture (dieldrin 0.025 mg/kg, endosulfan, 0.6 mg/kg, dicofol 0.22 mg/kg, dichlorvos 0.23 mg/kg, permethrin 5 mg/kg) or an effective dose mixture (dichlorvos 2.3 mg/kg, dicofol 2.5 mg/kg, endosulfan 2.9 mg/kg, dieldrin 0.05 mg/kg and permethrin 25.0 mg/kg), respectively; the other five groups received a semipurified diet containing each single pesticide in effective doses. At sacrifice, the thymus, spleen, mesenteric lymph nodes, Payer's patches and bone marrow were removed for histological analysis. Peritoneal macrophages were obtained to determine the phagocytosis and spreading indexes and tumoral necrosis factor alpha (TNF-α), nitric oxide (NO) and H₂O₂ production. Exposure to pesticide mixtures did not alter the percentage of macrophage phagocytosis and spreading, TNF-α production or the NO and H₂O₂ release when compared to the non-treated group. Neither was there any apparent evidence that a pesticide mixture at low or effective doses altered the histological structure of the lymphohematopoietic organs. The findings indicate that short-term treatment with pesticide mixtures did not induce an apparent immunotoxic effect in male Wistar rats.     

Toxic effects of chlorpyrifos on lysozyme activities,the contents of complement C3 and IgM,and IgM and complement C3 expressions in common carp (Cyprinus carpio L.)

Chlorpyrifos is one of the organophosphate pesticides widely used in agricultural practices throughout world. It has resulted in a series of toxicological and environmental problems, such as impacts on many non-target aquatic species, including fish. In the present study, toxic effects of chlorpyrifos on lysozyme activities, contents of IgM and complement C3, and the expressions of IgM and complement C3 at mRNA level in common carp were evaluated by acute exposure of 15 (1/10 LC₅₀) or 75 μg L⁻¹ (1/2 LC₅₀) of chlorpyrifos for 7 d. The results of acute toxicity tests showed that the 96 h-LC₅₀ of chlorpyrifos for common carp was determined to be 149 μg L⁻¹. We also found that chlorpyrifos promoted lysozyme activities at the earlier stages of exposure but inhibited it at the late stages in the serum, hepatopancreas, and spleen of common carp. Furthermore, it was observed that chlorpyrifos-exposure decreased IgM contents in fish serum and spleen while increased it in kidney. No obvious change was found in the contents of complement C3 in fish spleen, while a slight increase of complement C3 was observed in fish serum and kidney after 1 d of chlorpyrifos-exposure. In addition, the results of quantitative real-time PCR showed that IgM and complement C3 expressions were up-regulated at the earlier stage of exposure but down-regulated at later stage. Our results indicate that chlorpyrifos causes immunotoxicity to common carp.     

Multi-biomarker approach in wild European bullhead, Cottus sp., exposed to agricultural and urban environmental pressures: practical recommendations for experimental design

In freshwater ecosystems, a large number of chemical substances are able to disturb homeostasis of fish by modulating one or more physiological functions including the immune system. The aim of this study was to assess multi-biomarker responses including immunotoxicity induced by urban and agricultural pressure in European bullheads living in a small French river basin. For this purpose, a set of biochemical, immunological, physiological and histological parameters was measured in wild bullheads from five locations characterized by various environmental pressures. Moreover, to address effects of physiological status and contamination level variation on biomarker responses, fish were sampled during three periods (April, July and October). Results revealed a clear impact of environmental pressure on fish health and particularly on immunological status. An increase of EROD activity was recorded between upstream and downstream sites. Upstream sites were also characterized by neurotoxicological effects. Fish exhibited upstream/downstream variations of immunological status but strong differences were observed according to sampling season. Conversely, regarding biochemical and immunological effects, no significant response of physiological indexes was recorded related to environmental pressures. According to these results, the European bullhead appears as a valuable model fish species to assess adverse effects in wildlife due to urban and agricultural pressures.     

Immunotoxicity in ascidians: antifouling compounds alternative to organotins: III--the case of copper(I) and Irgarol 1051

After the widespread ban of TBT, due to its severe impact on coastal biocoenoses, mainly related to its immunosuppressive effects on both invertebrates and vertebrates, alternative biocides such as Cu(I) salts and the triazine Irgarol 1051, the latter previously used in agriculture as a herbicide, have been massively introduced in combined formulations for antifouling paints against a wide spectrum of fouling organisms. Using short-term (60 min) haemocyte cultures of the colonial ascidian Botryllus schlosseri exposed to various sublethal concentrations of copper(I) chloride (LC₅₀ = 281 μM, i.e., 17.8 mg Cu L⁻¹) and Irgarol 1051 (LC₅₀ > 500 μM, i.e., >127 mg L⁻¹), we evaluated their immunotoxic effects through a series of cytochemical assays previously used for organotin compounds. Both compounds can induce dose-dependent immunosuppression, acting on different cellular targets and altering many activities of immunocytes but, unlike TBT, did not have significant effects on cell morphology. Generally, Cu(I) appeared to be more toxic than Irgarol 1051: it significantly (p < 0.05) inhibited yeast phagocytosis at 0.1 μM (∼10 μg L⁻¹), and affected calcium homeostasis and mitochondrial cytochrome-c oxidase activity at 0.01 μM (∼1 μg L⁻¹). Both substances were able to change membrane permeability, induce apoptosis from concentrations of 0.1 μM (∼10 μg L⁻¹) and 200 μM (∼50 mg L⁻¹) for Cu(I) and Irgarol 1051, respectively, and alter the activity of hydrolases. Both Cu(I) and Irgarol 1051 inhibited the activity of phenoloxidase, but did not show any interactive effect when co-present in the exposure medium, suggesting different mechanisms of action.     

美欧环境内分泌干扰物研究框架

欧美于20世纪90年代开始系统研究环境内分泌干扰物（EDs)，为此成立了专门的工作机构负责EDs研究的规划与协调工作。研究框架包括确认EDs对人类和生态效应的方法，剂量一效应关系模型以及检测环境暴露水平等。研究对环境威胁最大受试物的主要毒理学终点有致癌性，生殖发育毒性，神经毒性和免疫毒性，目前危险评价的新进展是应用定量结构活性关系（QSAR）模型预测化学物的安全性。     

Cellular response of mouse splenocytes to heavy metals exposure

Among the environmental contaminants recognised for their toxicity and their global presence, heavy metals are certainly a major concern. They can elicit a number of immunomodulatory effects leading ultimately to an enhanced susceptibility (sensitivity) of immune cells to microbial agents and the appearance of neoplastic diseases and autoimmune phenomena. Heavy metals also provoke changes in the function(s) of immune cells. A striking biological effect of heavy metals is the induction of intracellular thiols (cysteine, glutathione, metallothioneins). Thiols are involved in many physiological processes, including protection from free radical damage and detoxification of chemicals. The purpose of this study was to assess the differences of susceptibility (sensitivity) in both pre-activated (concanavalin A was used) and non-pre-activated cells in the presence of heavy metals. Five were evaluated on murine splenocytes. The lymphoblastic proliferation test was performed for lymphocytes and a phagocytosis test for macrophages. Data showed that the levels of thiols in the pre-activated cells are greater than non-pre-activated cells following exposure to various heavy metals; macrophages were more resistant than lymphocytes to the toxic effects of heavy metals, and pre-activated cells were more resistant than cells at rest. One possible explanation is that macrophages produce more thiols than lymphocytes and this provides an increased protection from the deleterious effects of heavy metals.     

Immune modulation in the blue mussel Mytilus edulis exposed to North Sea produced water

The discharge of oil well produced water (PW) provides a constant source of contaminants to the marine environment including polycyclic aromatic hydrocarbons, alkylated phenols, metals and production chemicals. High concentrations of PW cause adverse effects to exposed biota, including reduced survival, growth and reproduction. Here we explore the effects of PW on immune function in the blue mussel, Mytilus edulis. Mussels were exposed for 21 days to sublethal PW concentrations (0.125-0.5%) and cellular parameters were measured. Cell viability, phagocytosis and cytotoxicity were inhibited after exposure to 0.25% and 0.5% PW, whilst the 0.125% PW treatment produced significant increases in these biomarker responses. This biphasic response was only observed after 7 days exposure; longer exposure periods led to a reduction in immune parameters. Results indicate that PW concentrations close to the discharge point cause modulation to cellular immunity. The implications for longer-term disease resistance are discussed.