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Effects of in vitro brevetoxin exposure on apoptosis and cellular metabolism in a leukemic T cell line (Jurkat) 
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下载免费PDF全文 Harmful algal blooms (HABs) of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat) as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan), respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 – 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3. 相似文献
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环境污染能够影响养殖贝类的免疫能力,是导致贝类大规模死亡的重要原因之一。探讨了大连周边4个海区污染物对采集的菲律宾蛤仔(Ruditapes philippinarum)免疫毒性影响。结果发现:污染物浓度和种类对蛤仔的免疫和生理指标具有重要影响,在重金属和石油污染物浓度较低的皮口海区,血细胞总数、亮氨酸氨基肽酶活性和血淋巴溶菌酶活性均显著高于其它3个海区(P<0.05),而蛤仔的脂质氧化水平则较低;在重金属和石油污染物浓度较高的黑石礁海区,蛤仔血淋巴谷胱甘肽含量显著高于其它3个海区(P<0.05);在重金属浓度较高的庄河海区,蛤仔表现出较高的超氧化物歧化酶活性(P<0.05)。 相似文献
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为了研究邻苯二甲酸二乙基己酯(DEHP)对巨噬细胞的免疫毒性,采用不同浓度剂量DEHP处理小鼠巨噬细胞株RAW264.7细胞和腹腔巨噬细胞,通过检测细胞吞噬、细胞因子分泌及活性氧水平变化探讨DEHP暴露对免疫系统的毒性作用。结果表明:高浓度(20、40、80 mg·L-1)DEHP处理48 h后对RAW264.7细胞可造成急性损伤。低浓度(1、5、10 mg·L-1)DEHP连续染毒处理10代后,RAW264.7细胞吞噬红细胞百分率及吞噬指数显著抑制(P0.05)。RAW264.7细胞分泌TNF-α、IL-12和IL-23等细胞因子能力明显降低,并表现出一定的剂量-效应关系。随着DEHP暴露浓度的增加,DEHP染毒造成RAW264.7细胞内活性氧产生,受损加剧。除此之外,DEHP暴露还能明显抑制小鼠腹腔巨噬细胞对红细胞的吞噬能力(P0.05)。以上结果表明,DEHP暴露对巨噬细胞具有免疫抑制作用,损伤了巨噬细胞正常免疫功能发挥。 相似文献
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C Bouchez F Gervais R Fleurance B Palate JJ Legrand J Descotes 《Journal of toxicologic pathology》2012,25(2):183-188
Although a T-dependent antibody response (TDAR) assay is generally recommended as the first-line immune function assay in nonclinical immunotoxicity evaluation, second-line assays such as delayed-type hypersensitivity (DTH) to measure cell-mediated responses can provide helpful additional information. In this study, male Cynomolgus monkeys were injected intramuscularly either once or twice with 1 mg Keyhole Limpet Hemocyanin (KLH) or twice with a commercially available tetanus vaccine (40 IU tetanus toxoid + 0.06 mg aluminum hydroxide). All animals were subsequently challenged by intradermal injections of the same antigen or aluminum hydroxide after 4, 6 and 8 weeks. Clinical reactions at the injection sites were scored 24, 48 and 72 h post challenge. Skin biopsies were taken on completion of the observation period after each challenge for standard histological examination and immunolabeling using CD3 (T lymphocytes), CD19 (B lymphocytes) and CD68 (macrophages) antibodies. Tetanus toxoid induced stronger clinical reactions than KLH, whereas aluminum hydroxide induced no clinical reaction. Perivascular mononuclear cell infiltrates, a histopathological finding consistent with a DTH reaction, were seen after all challenges with tetanus toxoid or KLH, but not with aluminum hydroxide. Immunohistochemistry evidenced the presence of T lymphocytes and macrophages within these infiltrates. These results suggest that tetanus toxoid adjuvanted with aluminum hydroxide can induce a consistent DTH response for use as a model of cell-mediated response in Cynomolgus monkeys. 相似文献
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手性农药毒性评价进展 总被引：2，自引：0，他引：2
长期以来,手性农药都被当作单一化合物进行环境行为和生态毒性研究,但是由于手性农药对映体与生物大分子相互作用的立体选择性,手性农药对动物及人类的毒性作用可能具有对映体选择性.本文介绍了有机磷、有机氯、拟除虫菊酯、苯基吡唑等手性农药对内分泌、神经、免疫、生殖、发育等毒性作用的对映体选择性,分析了对映体选择性产生的机制,在此基础上提出了未来的研究方向. 相似文献
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Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice 下载免费PDF全文
下载免费PDF全文 Milton Levin Heather Leibrecht James Ryan Frances Van Dolah Sylvain De Guise 《Marine drugs》2008,6(4):636-659
The immunotoxic potential of domoic acid (DA), a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 μg/g b.w.) and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 μM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr), a significant decrease in neutrophil phagocytosis (24-hr), a significant decrease in monocyte phagocytosis (48-hr), and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr). In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 μM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 μM, and significantly decreased at 100 μM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species. 相似文献
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T-2毒素的免疫毒性具有矛盾性和复杂性。低剂量T-2毒素可提升动物对病原体的抵抗力,高剂量T-2毒素则大大降低动物的免疫力。T-2毒素暴露时间早于病原体可增加动物免疫抵抗力,反之或毒素与病原体同时暴露,则降低动物对病原体的抵抗力。近期研究发现,细胞凋亡/存活通路维持毒素免疫调控动态平衡,自噬在免疫调控中发挥着关键而复杂的作用,但T-2毒素免疫调控中是否存在类似"免疫逃避"机制亟待研究。论文综述了T-2毒素免疫毒性的矛盾性,并重点讨论了其潜在的分子机制,为单端孢霉烯族毒素的免疫毒性和动物疫病防控研究提供参考。 相似文献
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拟除虫菊酯类农药的免疫毒性研究进展 总被引：1，自引：0，他引：1
拟除虫菊酯类杀虫剂因其高效、对哺乳动物低毒和易降解等特性已被广泛使用,目前对其生态毒理学的研究主要集中在神经及内分泌干扰、发育和生殖毒性方面,而关于其免疫毒性的研究也越来越受到了关注。文章对拟除虫菊酯类农药的免疫毒性及其分子机制研究进展进行了总结,主要从免疫器官、免疫细胞、免疫分子和免疫功能等方面综述了此类杀虫剂对不同生物的免疫毒性及其可能的分子机制,同时总结了拟除虫菊酯类杀虫剂暴露与免疫相关疾病发生的关联,以期为拟除虫菊酯类农药免疫毒性的进一步探究提供参考。 相似文献
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The current study was carried out to evaluate the effects of dietary supplementation of Coriandrum sativum seed powder (CP) and extract (CE) on some immune functions of Oreochromis niloticus, without or with exposure to the immunotoxicant metal lead (Pb). Fish (n = 300) were divided into ten groups, in triplicate. First group (Cont) was fed on the basal control diet. Second (CP20) and third (CP30) groups were fed on CP‐supplemented diets at 20 mg/kg and 30 mg/kg respectively, while fourth (CE20) and fifth (CE30) groups were fed on CE‐supplemented diets at 20 mg/kg and 30 mg/kg respectively. Fish of the sixth (Cont‐Pb), seventh (CP20‐Pb), eighth (CP30‐Pb), ninth (CE20‐Pb) and tenth (CE30‐Pb) groups were exposed to lead (Pb) at 20.2 mg/L and received same diets presented to groups; Cont, CP20, CP30, CE20 and CE30 respectively. The experiment lasted for 45 days. CP and CE dietary supplementation not only significantly enhanced the immune functions, serum lysozyme, nitric oxide, bactericidal activities and relative expression of interleukin‐1β (IL‐1β) of O. niloticus in a concentration‐dependent manner, but also ameliorated the lead‐induced immunosuppressive effects, especially in CE30 received groups. Additionally, lead‐induced fish mortality and levels of lead residues in fish musculature were significantly reduced in response to feeding on CP‐ and CE‐supplemented diets, especially in CE30. Therefore, it could be concluded that coriander dietary supplementation, especially the extract (CE) at 30 mg/kg diet, could be used to enhance the immune response of O. niloticus and to counteract the immunotoxic effects of lead exposure. 相似文献
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黄曲霉毒素(aflatoxins, AFs)是一类来自于霉菌中的剧毒物质, 其中以黄曲霉毒素B1(aflatoxin B1, AFB1)的毒性最强、危害性最大。AFB1是一种具有强致癌性及剧烈毒性的双呋喃环类毒素, 广泛分布于霉变的玉米、花生、大米和大豆等粮油作物中, 由AFB1引发的人与动物中毒事件给当前食品安全和畜禽养殖等行业的发展造成了严重危害。AFB1已被证明能够引起机体氧化应激、细胞凋亡、细胞焦亡、基因突变及免疫系统损伤。作者阐述了AFB1抑制机体免疫系统、破坏机体免疫耐受性的免疫毒性作用; 介绍了AFB1促进活性氧生成、激活Nrf2-ARE通路、诱导机体氧化应激和炎症反应进而造成器官损伤的器官毒性作用; 分析了AFB1利用细胞死亡相关受体调控外源性细胞凋亡作用, 以及通过一系列细胞凋亡相关蛋白诱导内源性细胞凋亡作用, 还可利用肝细胞经典焦亡途径引发炎症反应, 继而引发非正常死亡的细胞毒性作用; 回顾了近年来关于AFB1基因毒性与其去毒措施的作用机制及其研究进展。本综述有望为针对AFB1致病机制的深入研究及相关防治药物的研发提供参考, 并为发霉粮油作物的去毒措施的选择提供有效依据。 相似文献
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