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Developmental Effects of 7 Hz, Square Wave Magnetic Fields and Nitric Oxide Modulation on Organ Systems 7赫兹方波磁场和一氧化氮调制对器官系统发育的影响

The Open Toxicology Journal

Pub Date : 2008-06-23 DOI: 10.2174/1874340400802010007

P. Whissell, B. P. Mulligan, M. Hunter, H. P. Wu, G. Parker, M. Persinger

Prenatal or perinatal exposure to physiologically-patterned magnetic fields (MFs) affects behaviour in weanling (22d) and young adult (90d) rats. However, the long-term (120d-730d) biological effects of these MFs have not been ex- amined. In the current study, the long-term effects of developmental exposure to a physiologically-patterned MF, and their dependence on nitric oxide (NO) activity, were investigated. Pregnant dams were exposed from 2d before to 14d after par- turition to square wave, 7 Hz MF and to either water or nitric oxide (NO) modulation in tap water with NO precursor 1.0 g/L L-arginine or 0.5 g/L NO inhibitor n-methylarginine. To assess the possibility of intensity-windowing of any effects, MF intensities of <1, 1, 5, 10, 50 and 500 nT were employed. Male offspring were euthanized for post-mortem examina- tion and wet organ weights were then taken. Analysis showed increased brain weight in 10 and 50 nT-treated groups, in- creased bodyweight in 50 nT-treated groups and suggested increased testicular weight in 5, 10 and 50 nT-treated groups. Few effects of NO modulation were evident in these rats, reinforcing the idea that these are short-term and reversible. These findings suggest that subtle long-term changes in organ structure can arise from developmental exposure to physio- logically-patterned MFs.

产前或围产期暴露于生理模式磁场(MFs)会影响断奶大鼠(22天)和年轻成年大鼠(90天)的行为。然而，这些MFs的长期(120d-730d)生物学效应尚未被研究。在目前的研究中，研究了发育暴露于生理模式MF的长期影响，以及它们对一氧化氮(NO)活性的依赖。孕鼠在分娩前2天至产后14天暴露于方波、7 Hz中频和自来水中含有NO前体1.0 g/L L-精氨酸或0.5 g/L NO抑制剂n-甲基精氨酸的水或一氧化氮(NO)调制。为了评估任何影响的强度窗口的可能性，使用了< 1,1,5,10,50和500nt的MF强度。对雄性后代实施安乐死，进行死后检查，然后测量湿器官重量。分析显示，10和50个nt治疗组的脑重量增加，50个nt治疗组的体重增加，并提示5、10和50个nt治疗组的睾丸重量增加。在这些大鼠中，一氧化氮调节的影响很少，这加强了这些影响是短期和可逆的想法。这些发现表明，器官结构的微妙的长期变化可能引起发育暴露于生理模式的MFs。

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引用次数: 4

Therapeutic Alliance: Using N-(2,3,4,5,6-Pentahydroxylhex-1-yl)-NDithiocarbamate-L-Isoleucine Disodium to Improve the Toxicity and Survival of Cisplatin Receiving Mice 治疗联合:使用N-(2,3,4,5,6-五羟基己基-1-基)- n二硫代氨基甲酸酯- l -异亮氨酸二钠改善顺铂接受小鼠的毒性和生存

The Open Toxicology Journal

Pub Date : 2008-05-23 DOI: 10.2174/1874340400802010001

Yuji Wang, Ming Zhao, Guohui Cui, Chunying Cui, J. Ju, Shiqi Peng

To reduce the toxicity of cisplatin N-(2,3,4,5,6-pentahydroxylhex-1-yl)-N-dithiocarbamate-L-isoleucine diso- dium (GID) based therapeutic alliance is investigated. For the proliferation of HepG2, Hela, MES-SA, HL60 and H1299 cells, 27μM of GID based therapeutic alliance gave comparable inhibition to cisplatin alone. For implanted tumor prolif- eration in mice, 1.667μmol/kg of GID based therapeutic alliance gave higher inhibition than cisplatin alone. For cisplatin receiving mice, this therapeutic alliance effectively reduces the platinum accumulations in the organs but does not affect the platinum level in the tumor tissue. Comparing to cisplatin alone, this therapeutic alliance not only increases urea and fecal platinum levels but also increases urea excretion. All the observations imply that GID based therapeutic alliance is capable of reducing the toxicity and supporting the anti-tumor potency of cisplatin.

为了降低顺铂的毒性，研究了N-(2,3,4,5,6-五羟基己基)-N-二硫代氨基甲酸酯- l -异亮氨酸二钠(GID)为基础的联合治疗。27μM GID联合治疗对HepG2、Hela、MES-SA、HL60和H1299细胞的增殖抑制作用与单用顺铂相当。对小鼠植入式肿瘤增殖，1.667μmol/kg GID联合治疗比单用顺铂具有更高的抑制作用。对于接受顺铂治疗的小鼠，这种治疗联合有效地减少了铂在器官中的积累，但不影响肿瘤组织中的铂水平。与单用顺铂相比，这种联合治疗不仅增加尿素和粪便中的铂含量，而且增加尿素排泄。以上结果提示，以GID为基础的联合治疗能够降低顺铂的毒副作用，支持顺铂的抗肿瘤效力。

引用次数: 1

Methylmercury Neurotoxicity: Exploring Potential Novel Targets. 甲基汞神经毒性：探索潜在的新靶点。

The Open Toxicology Journal

Pub Date : 2007-01-01 Epub Date: 2007-10-17 DOI: 10.2174/1874340400701010001

J L Aschner, M Aschner

Mechanistic studies on the effects of MeHg in the central nervous system (CNS) have been limited to morphology, substrate uptake and macromolecular synthesis, differentiation, and changes in gene expression during development and adulthood, but its primary site of action has yet to be identified. Proper functioning of the nitric oxide synthase (NOS)-cyclic GMP and the cyclooxygenase (COX)-prostaglandin (PG) signaling pathways in the CNS depend on post-translational modifications of key enzymes by chaperone proteins. The ability of MeHg to alter or inhibit chaperone-client protein interactions is hitherto unexplored, and potentially offers an upstream unifying mechanism for the plethora of MeHg effects, ranging from reactive species generation (ROS) generation, mitochondrial dysfunction, changes in redox potential, macromolecule synthesis, and cell swelling. In view of the prominent function of astrocytes in the maintenance of the extracellular milieu and their critical role in mediating MeHg neurotoxicity, they afford a relevant and well-established experimental model. The present review is predicated on (a) the remarkable affinity of mercurials for the anionic form of sulfhydryl (-SH) groups, (b) the essential role of thiols in protein biochemistry, and (c) the role of molecular chaperone proteins, such as heat shock protein 90 (Hsp90) in the regulation of protein redox status by facilitating the formation and breakage of disulfide bridges. We offer potential sites where MeHg may interfere with cellular homeostasis and advance a novel mechanistic model for MeHg-induced neurotoxicity.

关于甲基汞对中枢神经系统（CNS）影响的机制研究仅限于形态、底物摄取和大分子合成、分化，以及发育和成年期间基因表达的变化，但其主要作用位点尚未确定。中枢神经系统中一氧化氮合酶（NOS）-环GMP和环氧合酶（COX）-前列腺素（PG）信号通路的正常功能取决于伴侣蛋白对关键酶的翻译后修饰。甲基汞改变或抑制伴侣-客户端-蛋白质相互作用的能力迄今尚未被探索，并可能为过多的甲基汞效应提供上游统一机制，包括活性物质产生（ROS）、线粒体功能障碍、氧化还原电位的变化、大分子合成和细胞肿胀。鉴于星形胶质细胞在维持细胞外环境中的突出功能及其在介导甲基汞神经毒性中的关键作用，它们提供了一个相关且成熟的实验模型。本综述基于（a）汞对巯基（-SH）阴离子形式的显著亲和力，（b）硫醇在蛋白质生物化学中的重要作用，以及（c）分子伴侣蛋白，如热休克蛋白90（Hsp90），通过促进二硫键的形成和断裂，在调节蛋白质氧化还原状态中的作用。我们提供了甲基汞可能干扰细胞稳态的潜在位点，并提出了甲基汞诱导神经毒性的新机制模型。

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引用次数: 14

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