慢性氟、砷染毒对小鼠肾皮质氧化应激的损害

目的　探讨慢性氟中毒、砷中毒及联合中毒对小鼠肾皮质氧化应激损害程度及其异同 ,为氟、砷中毒的防治提供科学依据。方法　昆明种小鼠 1 2 0只 ,随机分成对照、氟、砷和氟砷联合染毒 4组 ,分别自由进食普通、高氟、高砷和高氟高砷饲料 ,分别于 6个月和 1 2个月取材 ,检测肾皮质丙二醛 (MDA)和脂质过氧化物 (LPO)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶 (GSH PX)、琥珀酸脱氢酶 (SDHase)和葡萄糖 6 磷酸酶 (G 6 Pase)活力。结果　与对照组比较 ,3种染毒模式在 6和 1 2个月观察期均引起肾皮质MDA含量增加 (P <0 0 1 ) ,GSH PX 活力在 6个月时均下降 (P <0 0 1 ) ;仅见氟组在 1 2个月时恢复正常 ,而砷和氟 +砷组仍维持低水平 (P <0 0 1 ) ;2个观察时点的SOD活力均下降 (P <0 0 1 )。此外 ,1 2个月的GSH、SDH和G 6 Pase均下降 (P <0 0 1 ,P <0 0 1 ,P <0 0 5)。结论　慢性氟、砷和氟砷联合染毒均能引起小鼠肾皮质氧化应激作用增强 ,氟、砷 2毒物对在引起肾皮质LPO损害作用方面无明显交互作用     

氟砷代谢研究进展

氟和砷是影响人类健康的两种重要元素。砷是一种常见的环境毒物和已知的人类致癌物[1] ,氟是人体必需微量元素 ,同时也是可疑致癌物。由于地球化学元素分布不均和工业发展引起环境污染等原因 ,氟和砷在环境中分布广泛 ,使特定地方病区居民、工人甚至一般环境人群接触过量的氟或砷 ,因而氟砷中毒已成为医学研究的重要内容。本文简述近年来有关氟砷代谢研究进展。1　分　布自然界的砷以多种价态形式 ,广泛分布于大气、水、土壤、岩石和生物体中。地壳砷的平均含量为2ｐｐｍ ,但在富砷矿石如含砷黄铁矿 (ＦｅＡｓＳ)、雌黄(Ａｓ4Ｓ6)含量有的可…     

氟砷联合染毒对大鼠子代大脑氧化性损伤的研究

目的 揭示氟砷共存时对子代健康的影响。方法 采用两代一窝繁殖实验的方法,测定Ｗｉｓｔａｒ大鼠暴露于氟砷后其子代大脑中氟砷蓄积情况、脂质过氧化水平。结果 随着暴露剂量的增加,大脑氟砷含量显著增加,ＳＯＤ和ＧＳＨ－Ｐｘ活性随之降低,而ＬＰＯ含量却逐渐增加,同代不同剂量组间比较,差异均有非常显著意义（Ｐ〈０．０１）,并出出明显的病理性变化;停止氟砷暴露８周后,大脑氟砷含量显著降低,酶的生有所恢复,而ＬＰ     

氟砷对大鼠肾脂质过氧化和抗氧化能力的影响

氟砷对大鼠肾脂质过氧化和抗氧化能力的影响刘开泰，肖碧玉，姜平，张晨，王国荃，冯东明许多研究证明［１－３］，氟和砷均可引起肾脏组织结构和功能改变，但氟和砷联合作用对肾脏脂质过氧化和抗氧化能力影响的研究则较少。为此，我们采用亚慢性动物实验，观察单独氟、砷...     

氟、砷对大鼠生殖发育和微量元素的影响

许多研究已经证明 ,氟、砷均是全身性毒物 ,对机体的各组织器官均有一定的损害作用[1] 。以前的研究已证实 ,氟和砷都已被肯定为生殖毒物[2 ,3 ] ,但有关氟砷共存时的毒性研究相对较少。因此 ,我们通过动物实验的手段研究氟、砷染毒对大鼠生殖发育和微量元素的影响 ,为基础理论研究提供资料。1　材料与方法1 1　试验动物与分组　选用Wistar大鼠 ,由新疆实验动物中心提供。 8～ 9周龄 ,其中雌性 10 4只 ,体重 12 0～ 15 0g ;雄 5 2只 ,体重 14 0～ 2 0 0g。随机分为 4组。1 2　受试物及染毒剂量　受试物为NaF和As2 O3 ,喂饲法染毒。染毒剂…     

饮水型地方性砷中毒病区改水后人群体内砷代谢状况的研究

目的:研究地方性砷中毒病区改水后砷在人体内蓄积及代谢的动态变化情况。方法在改水1年内对曾饮用高砷水的村民测定尿砷、发砷含量。结果停止饮用高砷水后,尿砷在4个月内,发砷在7个月呈急剧下降趋势,至12个月后,尿砷降至正常水平,发砷均值仍高于国家标准。说明停用高砷水后,体内蓄积的砷大部分被人体代谢,同时还有一部分由于与角蛋白结合紧密而不易解脱。结论终止饮高砷水后,病区人群体内蓄积的砷逐渐排出体外,但也有部分因与角蛋白结合紧密对人体产生危害,故应在改水的基础上开展驱砷治疗,使体内蓄积的砷尽早排出体外。     

滇东北煤烟污染型地方性氟中毒

<正> 滇东北地区泛指云南境内东102°19′～103°19′,北纬24°21′～28°41′,其北面与四川接壤,东与贵州相连,包括昭通、曲靖、东川三个地区、市的10个县,约5万平方公里,800万人口。七十年代末省防疫站等单位曾对昭通局     

2009年讷河市地方性氟中毒重病区病情现状调查

目的：掌握讷河市地方性氟中毒重病区的病情现状,为今后预防控制地方性氟中毒提供科学依据。方法：在讷河市中随机抽取3个乡,采用分层抽样方法,对受调查市轻、中、重病区分别随机抽取27个病区村为调查点。调查8～12岁儿童的氟斑牙和成人氟骨症患病情况,检测饮水氟和8～12岁儿童尿氟,调查改水情况。结果：8～12岁儿童的氟斑牙总患病率为11．52％,未检出氟骨症的患者,饮水氟平均值为1．66mg／L。8～12岁儿童的尿氟几何值为2．65mg／L,重病区县总改水率为88．89％。结论：讷河市地方性氟中毒重病区市的病情基本得到控制,原有氟中毒患者的病情有转轻的趋势,部分重病区村的改水降氟设施的使用和管理工作需进一步加强。     

急性氟中毒大鼠肾损害与脂质过氧化的改变

脂质过氧化(Lipid Peroxidation,LPO)是许多毒物发生毒作用机理。有研究发现氟中毒可损害肾脏,我们利用急性氟中毒大鼠动物模型,探讨尿氟排泄规律、肾脏损害情况及其与LPO的关系。 材料与方法 一、染毒动物模型 用Wistar大鼠,体重180～220g,由遵义医学院动物中心提供。随机分为4     

低砷染毒大鼠肾脏蛋白质组学研究

目的对低剂量砷暴露大鼠肾脏进行蛋白质组学研究,探讨早期砷暴露的生物学标志物。方法选取健康雄性SD大鼠48只,按体质量随机分为4组,每组12只,即对照组(0μg/L),低剂量染毒组(50μg/L),中剂量染毒组(150μg/L),高剂量染毒组(450μg/L)。染毒4周后处死大鼠,取其肾脏运用蛋白质组学技术(双向凝胶电泳)分离蛋白,凝胶经扫描后用Pdquest图形分析软件对2-DE图谱进行了分析,鉴定染毒SD大鼠和正常SD大鼠肾脏蛋白质的差异表达。结果定性分析发现,与对照组比较,低剂量组新出现了2个蛋白质点,消失了4个蛋白质点;中剂量组新出现了4个蛋白质点,消失了3个蛋白质点;高剂量组新出现了3个蛋白质点,消失了7个蛋白质点。定量分析发现,与对照组比较,低剂量组表达量升高的蛋白质点有4个,降低的有4个;中剂量组表达量升高的蛋白质点有11个,降低的有2个;高剂量组表达量升高的蛋白质点有3个,降低的有4个。结论低砷染毒导致大鼠肾组织中蛋白质差异表达,这些蛋白质可能与砷暴露的毒性作用有关。     

Circulating miRNA-126, -145 and -155 levels in Mexican women exposed to inorganic arsenic via drinking water

The aim of this research was to investigate circulating expression levels of three miRNAs (miR-126, miR-155, and miR-145) proposed as predictive CVD biomarkers in Mexican women exposed to inorganic arsenic via drinking water. Mean UAs concentration of 19.5 ± 14.0 μg/g creatinine was found after urine samples were analyzed (n = 105). Significant associations between UAs levels and serum expression levels of miR-155 (p < 0.05) and miR-126 (p < 0.05) were observed after adjustment for assessed co-variables. Alterations in the serum expression levels of miR-155 and miR-126 may be associated with the onset and development of cardiovascular diseases, hence miRNAs could be proposed as prognostic CVD biomarkers. Data found in this study are of concern and risk reduction plans are necessary for the assessed communities to prevent cardiovascular events in this population of women.     

Research approaches to address uncertainties in the risk assessment of arsenic in drinking water

Inorganic arsenic (iAs), an environmental drinking water contaminant, is a human toxicant and carcinogen. The public health community has developed recommendations and regulations that limit human exposure to iAs in drinking water. Although there is a vast amount of information available to regulators on the exposure, disposition and the health-related effects of iAs, there is still critical information about the toxicology of this metalloid that is needed. This necessary information includes identification of the chemical species of arsenic that is (are) the active toxicant(s), the mode(s) of action for its various toxicities and information on potentially susceptible populations. Because of these unknown factors, the risk assessment of iAs still incorporates default assumptions, leading to uncertainties in the overall assessment. The characteristics of a scientifically defensible risk assessment for iAs are that it must: (1) quantitatively link exposure and target tissue dose of active metabolites to key events in the mode of action for major health effects and (2) identify sources of variation in susceptibility to arsenic-induced health effects and quantitatively evaluate their impact wherever possible. Integration of research to address these goals will better protect the health of iAs-exposed populations.     

Mitigating effects of some antidotes on fluoride and arsenic induced free radical toxicity in mice ovary.

The effects of oral administration of sodium fluoride (NaF) and/or arsenic trioxide (As(2)O(3)) (5 mg and 0.5 mg/kg body weight, respectively) for 30 days were investigated on free radical induced toxicity in the mouse ovary. The reversibility of the induced effects after withdrawal of NaF+As(2)O(3) treatment and by administration of antioxidant vitamins (C, E) and calcium alone as well as in combination were also studied. The combined treatment of NaF and As(2)O(3) impaired significantly (p<0.001) the production of free radical scavengers such as glutathione and ascorbic acid as well as antioxidant enzymes, namely, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (Cat), thereby increasing ovarian lipid peroxides (LPO) which might have rendered the ovary susceptible to injury. The withdrawal of the combined (NaF and As(2)O(3) for 30 days) treatment caused partial recovery in the ovary, which was more pronounced (p<0.001) by treatment with vitamin C, calcium, or vitamin E alone and in combination. Hence the induced toxicity was transient and reversible.     

原子荧光光谱法同时测定饮用水中的砷和硒

目的：采用氢化物发生-原子荧光光谱法测定饮用水中的砷和硒。方法：用硝酸、高氯酸混合溶液消解水样,在5%盐酸介质中,加入硫脲-抗坏血酸混合试剂,以20g/L NaBH4溶液为还原剂,测定砷、硒荧光强度。结果：在最佳实验条件下,检出限砷为0.526μg/L,硒为0.452μg/L。回收率砷为94.8%～100.3%;硒为95.1%～99.0%。结论：此方法简便,快速,准确。     

Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites have unique toxicities and relatively greater potency compared to their pentavalent counterparts for many endpoints. In this study, dose-dependency in tissue distribution and urinary excretion for inorganic arsenic and its methylated metabolites was assessed in female C57Bl/6 mice exposed to 0, 0.5, 2, 10 or 50 ppm arsenic (as arsenate, AsV) in their drinking water for 12 weeks. No adverse effects were observed and body weight gain did not differ significantly among groups. Urinary excretion of arsenite monomethylarsonous acid (MMA(III)), dimethylarsinous acid (DMA(III)), dimethylarsinic acid (DMAV), and trimethylarsine oxide (TMAO) increased linearly with dose, whereas AsV and monomethylarsonic acid (MMAV) excretion was non-linear with respect to dose. Total tissue arsenic accumulation was greatest in kidney > lung > urinary bladder > skin > blood > liver. Monomethyl arsenic (MMA, i.e. MMA(III)+MMAV) was the predominant metabolite in kidney, whereas dimethylarsenic (DMA, i.e., DMA(III)+DMAV) was the predominant metabolite in lung. Urinary bladder tissue had roughly equivalent levels of inorganic arsenic and dimethylarsenic, as did skin. These data indicate that pharmacokinetic models for arsenic metabolism and disposition need to include mechanisms for organ-specific accumulation of some arsenicals and that urinary metabolite profiles are not necessarily reflective of target tissue dosimetry.     

Low-level arsenic exposure in drinking water and bladder cancer: a review and meta-analysis

Although exposure to high levels of arsenic in drinking water is associated with excess cancer risk (e.g., skin, bladder, and lung), lower exposures (e.g., <100–200 μg/L) generally are not. Lack of significant associations at lower exposures may be attributed to methodologic issues (e.g., inadequate statistical power, exposure misclassification), or to differences in the dose–response relationship at high versus low exposures. The objectives of this review and meta-analysis were to evaluate associations, examine heterogeneity across studies, address study design and sample size issues, and improve the precision of estimates. Eight studies of bladder cancer and low-level arsenic exposure met our inclusion criteria. Meta-analyses of never smokers produced summary relative risk estimates (SRREs) below 1.0 (highest versus lowest exposure). The SRRE for never and ever smokers combined was elevated slightly, but not significantly (1.11; 95% CI: 0.95–1.30). The SRRE was somewhat elevated among ever smokers (1.24; 95% CI: 0.99–1.56), and statistical significance was observed in some subgroup analyses; however, heterogeneity across studies was commonly present. Although uncertainties remain, low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer. More studies with detailed smoking history will help resolve whether smoking is an effect modifier.     

Relationship between arsenic content of food and water applied for food processing

As part of a survey conducted by the Central Agricultural Office of Hungary, 67 food samples including beverages were taken from 57 food industrial and catering companies, 75% of them being small and medium-sized enterprises (SMEs). Moreover, 40% of the SMEs were micro entities. Water used for food processing was simultaneously sampled. The arsenic (As) content of solid food stuff was determined by hydride generation atomic absorption spectrometry after dry ashing. Food stuff with high water content and water samples were analyzed by inductively coupled plasma mass spectrometry. The As concentration exceeded 10 μg/L in 74% of the water samples taken from SMEs. The As concentrations of samples with high water content and water used were linearly correlated. Estimated As intake from combined exposure to drinking water and food of the population was on average 40% of the daily lower limit of WHO on the benchmark dose for a 0.5% increased incidence of lung cancer (BMDL_0.5) for As. Five settlements had higher As intake than the BMDL_0.5. Three of these settlements are situated in Csongrád county and the distance between them is less than 55 km. The maximum As intake might be 3.8 μg/kg body weight.     

Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to ~ 35% and in wild-type mice to ~ 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminished capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. Altered retention and tissue tropism of arsenic in As3mt knockout mice could affect the toxic or carcinogenic effects associated with exposure to this metalloid or its methylated metabolites.     

Residential exposure to drinking water arsenic in Inner Mongolia, China

In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.