A Novel System to Study the Impact of Epithelial Barriers on Cellular Metabolism

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O₂)₂ 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm² for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society. PAC00: 8716Uv, 8715Vv     

Vanadium exposure-induced striatal learning and memory alterations in rats

Occupational and environmental exposure to vanadium has been associated with toxicities in reproductive, respiratory, and cardiovascular systems. The knowledge on whether and how vanadium exposure caused neurobehavioral changes remains incomplete. This study was designed to investigate the changes in learning and memory following drinking water exposure to vanadium, and to conduct the preliminary study on underlying mechanisms. Male Sprague-Dawley rats were exposed to vanadium dissolved in drinking water at the concentration of 0.0, 0.5, 1.0 and 2.0 g/L, as the control, low-, medium-, and high- dose groups, respectively, for 12 weeks. The results by the Morris water maze test showed that the time for the testing animal to find the platform in the high exposed group was increased by 82.9% and 49.7%, as compared to animals in control and low-dose groups (p < 0.05). There were significantly fewer rats in the medium- and high- dose groups than in the control group who were capable of crossing the platform (p < 0.05). Quantitation of vanadium by atomic absorption spectrophotometry revealed a significant dose-dependent accumulation of vanadium in striatum (r = 0.931, p < 0.01). Histopathological examination further demonstrated a degenerative damage in vanadium-exposed striatum. Interestingly, with the increase of the dose of vanadium, the contents of neurotransmitter ACh, 5-HT and GABA in the striatum increased; however, the levels of Syn1 was significantly reduced in the exposed groups compared with controls (p < 0.05). These data suggest that vanadium exposure apparently reduces the animals’ learning ability. This could be due partly to vanadium’s accumulation in striatum and the ensuing toxicity to striatal structure and synaptic plasticity. Further research is warranted for mechanistic understanding of vanadium-induced neurotoxicity.     

钒对神经行为功能影响的配对分析

目的 探讨长期钒接触对工人神经行为功能的损害作用及表现特征.方法 采用WHO推荐的神经行为测试组合对钒接触人群和对照人群做测试,分析时采用配对t检验,对符合标准的106对研究对象进行统计分析.结果 ①反映积极情绪的有力-好动得分,钒接触组低于对照组,反映消极情绪的紧张-焦虑、抑郁-沮丧、愤怒-敌意、疲劳-惰性、困惑-迷茫得分,钒接触组高于对照组,差异均有统计学意义(P＜0.05);②钒接触组视觉保留得分低于对照组(P＜0.05);③钒接触组提转敏捷度得分低于对照组(P＜0.05);④目标追踪方面,钒接触组正确点数低于对照组,错误点数高于对照组,差异有统计学意义(P＜0.05).结论 长期接触五氧化二钒可对工人神经行为功能造成损害,主要表现在消极情绪增加、视觉记忆力下降、运动速度减慢和运动稳定性下降4个方面.     

五氧化二钒对体外小鼠胚胎生长发育的影响

本研究采用体外着床后全胚胎培养方法，观察了Ｖ２Ｏ５对小鼠胚胎生长发育的影响，结果显示，Ｖ２Ｏ５浓度达１５ｍｇ／ｌ时可影响胚胎的生长发育和形态分化，导致胚胎畸形率增加。在１５ｍｇ／ｌ以下浓度仅显示个别动物生长发育受影响，无明显的剂量－反应关系。     

Genotoxic effects of vanadium pentoxide on human peripheral lymphocytes and mucosal cells of the upper aerodigestive tract

In addition to tobacco and alcohol consumption, pollutants found in certain industries and in the environment play an important role in carcinogenesis in the upper aerodigestive tract. The aim of the present study was to investigate whether vanadium pentoxide may have a genotoxic effect on human mucosal cells and lymphocytes. The single cell microgel electrophoresis assay (Comet assay) was used to detect DNA damage induced by vanadium pentoxide in human nasal epithelia (n = 11) and in lymphocytes (n = 11). Mucosa was harvested from inferior nasal turbinates, while lymphocytes were obtained via venous puncture. Vanadium pentoxide was applied at concentrations of 0.06 mM, 0.12 mM, 0.24 mM, and 0.47 mM. Aqua bidestillata served as solvent and negative control and N-methyl-N'-nitro-N-nitrosoguanidine at 0.07 mM (MNNG) was used as positive control. The trypan blue exclusion test was applied to assess cytotoxicity. Whereas vanadium pentoxide induced dose-dependent DNA migration in lymphocytes, mucosal cells did not show comparable genotoxic effects. Cytotoxic effects allowed for viabilities exceeding 80%. The results indicate that vanadium pentoxide is capable of inducing single-strand-breaks and/or alkali-labile damage in the DNA of human lymphocytes. By contrast, mucosal cells proved not to be sensitive in this setting. Thus, a possible role of vanadium in the tumorigenesis of head and neck cancer appears unrelated to direct genotoxic effects.     

钒化合物通过不同方式刺激线粒体活性氧生成(英文)

钒化合物在癌症及糖尿病治疗中显示出其潜在的可能而受到人们的关注,但是其毒性限制了其作为药物的进一步发展。已有研究表明钒通过影响线粒体功能诱导的氧化应激是钒化合物毒性的主要原因。本工作主要考察了两种钒化合物-偏钒酸钠和乙酰丙酮氧钒对线粒体活性氧产生和呼吸链复合体活性的影响。结果表明,钒化合物依其化学物种的不同而对活性氧和复合体活性以不同的方式产生影响。偏钒酸钠抑制线粒体复合体Ⅰ和Ⅱ的活性,同时在低浓度范围内促进活性氧的产生。而氧钒化合物则促进复合体Ⅱ活性,同时促进复合体Ⅰ相关途径的电子漏。本工作为研究钒化合物作为抗糖尿病药物毒性提供了新的结果。     

Determination of trace vanadium(V) by adsorptive anodic stripping voltammetry on an acetylene black paste electrode in the presence of alizarin violet

A sensitive and simplified voltammetric method is developed for the determination of trace amounts of vanadium(V) by adsorptive anodic stripping voltammetry using an acetylene black (AB) paste electrode. The method is based on the preconcentration of the V(V)–alizarin violet (AV) complex at open circuit while stirring the solution for 90 s in 0.15 mol dm⁻³ hexamethylenetetraamine–hydrochloric acid buffer (pH 4.4), the adsorbed complex is then oxidized, producing a response with a peak potential of 564 mV when scanning linearly from 0 to 1000 mV. For voltammetric determination of V(V), the parameters influencing the peak current have been optimized. Under the selected conditions, the peak current and concentration of V(V) accorded with linear relationship in the range of 8.0 × 10⁻¹⁰ mol dm⁻³–1.0 × 10⁻⁷ mol dm⁻³ (c_AV = 2.0 × 10⁻⁶ mol dm⁻³) and 1.0 × 10⁻⁷ mol dm⁻³–8.0 × 10⁻⁶ mol dm⁻³ (c_AV = 2.0 × 10⁻⁵ mol dm⁻³), the detection limit (three times signal to noise) was estimated to be 6.0 × 10⁻¹⁰ mol dm⁻³ for 90 s accumulation. The relative standard deviation (RSD) is 1.9% and 2.3% for V(V) concentrations of 1.0 × 10⁻⁷ mol dm⁻³ and 1.0 × 10⁻⁸ mol dm⁻³ respectively. Finally, this proposed method was successfully applied to the determination of V(V) in natural water samples.     

五氧化二钒对NIH小鼠发育毒性的研究

本文报道了受精后直至出生前不同时间经腹腔注射V_20_5后,对NIH小鼠胚胎一胎儿发育的影响。结果表明,V_2O_5对小鼠胚泡着床前和着床过程无明显影响,也无致畸性和致早产作用,但对胚胎—胎儿的存活和胎儿的骨骼发育有一定影响。可认为,V_2O_5对NIH小鼠是一较弱的发育毒物。另外,报道了敌枯双(阳性对照物)对NIH小鼠的发育毒性。     

钒在妊娠和非妊娠大鼠体内分布的研究

作者采用极谱法对妊娠和非妊娠大鼠脏器组织中的钒含量进行了测试,并对非妊娠与妊娠第12天和第16～18天大鼠一次性腹腔注射V_20_5(5mg/kg)后4小时及24小时钒在组织中的分布进行了研究。结果表明:卵巢、子宫以及胎盘等是钒的重要分布器官;钒可透过胎盘进入胎儿体内;钒主要从肾脏排泄;给药后24小时,体内仍有相当浓度,尚未达到平衡;钒在妊娠和非妊娠动物组织中的分布顺次有所不同。