高氯酸铵对去卵巢大鼠甲状腺干扰作用的研究

目的研究高氯酸铵(Ammonium Perchlorate,AP)对去卵巢大鼠(ovariectomization,OVX)甲状腺干扰作用的剂量-反应关系,获得其有害作用的最小剂量(LOAEL)值和BMDL10值。方法 60只雌性SD大鼠随机分为假手术(SHAM)对照组、OVX对照组和4个AP处理组(剂量为50、100、250和500 mg/kg·bw),连续灌胃8 d。灌胃结束次日检测大鼠肝脏Ⅰ型5’-脱碘酶(5’-DI)活性、血清3’-三碘甲腺原氨酶(T3)、甲状腺素(T4)和促甲状腺激素(TSH)水平,观察甲状腺组织病理学、甲状腺脏器系数和甲状腺表皮/胶质比等。分析获得未观察到有害作用剂量(NOAEL)和观察到有害作用的最小剂量(LOAEL),以及采用基准剂量法获得基准剂量(BMD)的可信区间下限(BMDL)。结果 OVX组体重和增重均显著高于SHAM对照组(P0.01),OVX各组间大鼠体重差异无统计学意义(P0.05)。AP各剂量组血清T4、TSH、甲状腺脏器系数和表皮/胶质比的改变均有统计学意义(P0.05),而5’-DI酶活性的改变均无统计学意义(P0.05);250和500 mg/kg·bw剂量组的血清T3显著低于OVX对照组(P0.01)。AP各剂量组甲状腺均出现不同程度的组织病理学损伤。AP对OVX大鼠血清T3、T4和TSH水平、甲状腺脏器系数和甲状腺表皮/胶质比的影响的LOAEL均为50 mg/kg·bw,AP对甲状腺干扰作用的BMDL10为15 mg/kg·bw。结论 AP对OVX大鼠甲状腺干扰作用呈显著的剂量-反应关系。AP对去卵巢大鼠甲状腺干扰作用的LOAEL为50 mg/kg·bw,BMDL10为15 mg/kg·bw。     

邻苯二甲酸二环己酯对雄性大鼠生殖内分泌的毒性

目的观察邻苯二甲酸二环己酯(DCHP)对雄性大鼠的生殖-内分泌毒性,探讨内分泌干扰物评价的效应终点。方法用雄性Wistar大鼠DCHP灌胃染毒,剂量分别为125、250和500 mg/(kg.d),对照组给与玉米油。观察临床症状,体重增长,血常规,血清生化,血Zn和激素以及解剖及组织病理学等指标。结果1252、50和500 mg/(kg.d)剂量组大鼠WBC数量减少,125和500 mg/(kg.d)剂量组大鼠CHO水平升高,125、250和500 mg/(kg.d)剂量组大鼠ALB水平升高,同时250和500 mg/(kg.d)剂量组A/G值增大,250和500 mg/(kg.d)剂量组血清睾酮水平降低,250和500 mg/(kg.d)剂量组血清雌激素水平升高,1252、50和500 mg/(kg.d)剂量组肝脏器系数均明显增高,250、500 mg/(kg.d)剂量组肾脏器系数增高,其他检测指标未见有明显毒理学意义的改变。结论在没有引起生殖毒性的剂量范围[(125~500 mg/(kg.d)]内,DCHP可以改变睾酮和雌激素水平,干扰生殖内分泌调节平衡。本研究结果为评价DCHP生殖内分泌毒性提供新的数据,同时为评价筛检可疑内分泌干扰物提供了效应终点。     

基准剂量法在90d经口毒性试验中的应用

目的采用基准剂量(BMD)法对某化学品90 d经口毒性试验数据进行分析,通过已明确无明显有害作用剂量和基准剂量的农药/化学品案例,将BMD法与传统的非致癌危险度评价法(NOAEL法)进行比较和讨论。方法经口灌胃大鼠某化学品0、100、300和1 000 mg/kg·bw·d,1次/d,连续90 d。观察记录大鼠中毒体征及死亡情况、体重变化、血常规、血生化、尿液检查和病理组织学检查。根据BMD法对试验的毒效应数据进行筛选,采用BMDS2.5软件,分析每一个筛选出的毒性终点数据,得出基准剂量。结果雌鼠高剂量组1 000 mg/kg·bw·d第1、3、7、8和9周体重降低、肺重量升高、脑\肝\肺脏器系数升高、凝血酶原时间升高,某化学品大鼠90 d经口毒性试验的NOAEL为300 mg/kg·bw·d。将具有统计学意义、毒理学意义以及显著剂量-反应趋势的数据(雌鼠肺重量、肝/肺脏器系数和凝血酶原时间)用BMD法进行分析,最终选择最敏感的毒性效应"凝血酶原时间"的基准剂量下限值(BMDL),141.7 mg/kg·bw·d,作为计算参考剂量的基础。结论在计算参考剂量时,以剂量-反应关系模型为基础的BMD法优于利用单个剂量点的NOAEL法,然而BMD法却需要更高质量的试验数据和更复杂的数据分析过程。     

全氟辛基磺酸钾对环青春期雌性大鼠毒性的研究

目的初步探讨全氟辛基磺酸钾(PFOS-K)对环青春期雌性大鼠的毒性。方法根据环青春期雌性大鼠青春期发育和甲状腺功能试验,PFOS-K喂饲给予,其在饲料中浓度分别为0、2、6和18 mg/kg·bw,连续染毒21 d。结果与对照组相比,18 mg/kg·bw组体重明显下降;6和18 mg/kg·bw组肝脏体比增加,肝细胞肿大,18 mg/kg·bw组谷丙转氨酶、白蛋白、碱性磷酸酶和总胆汁酸浓度均明显升高,各剂量组胆碱酯酶和甘油三酯浓度显著下降,差异有统计学意义(P0.05),呈剂量-反应关系;与对照组相比,各剂量组网织红细胞、红细胞和血红蛋白浓度下降,差异有统计学意义(P0.05);18 mg/kg·bw组青春发育延迟,垂体和附属性器官脏体系数降低,子宫内膜和肌层变薄,甲状腺滤泡上皮细胞增厚,滤泡面积减小;18 mg/kg·bw组肾脏体比降低,尿素氮升高;18 mg/kg·bw组脾脏体比降低,6和18 mg/kg·bw组中性粒细胞明显增加,单核细胞比率降低,上述差异均有统计学意义(P0.05)。结论 PFOS-K对环青春期雌性大鼠有肝毒性、骨髓毒性、内分泌干扰作用(抗雌激素和甲状腺干扰作用)、肾毒性和免疫毒性;最小可见损害作用水平(LOAEL)为2.39 mg/kg·bw。     

95%肟草酮的亚慢性经口毒性

目的研究肟草酮原药对大鼠的主要亚慢性毒性作用及无明显损害作用剂量。方法按照GB15670-1995《农药登记毒理学实验方法》中大鼠亚慢性经口毒性试验方法进行,设0、11.31、33.92和101.75mg/kg4个剂量组。结果雌性大鼠中剂量组(33.92mg/kg)和高剂量组(101.75mg/kg)总摄食量、总食物利用率、体重总增加量低于对照组,雄性大鼠中剂量组(33.92mg/kg)和高剂量组(101.75mg/kg)组肝/体比均高于对照组,中剂量组雄性大鼠肺/体比和脾/体比高于对照组,雌性大鼠中剂量组肝/体比高于对照组。血液常规指标中剂量组雄性大鼠RBC、HGB均低于对照组、ALP高于对照组,高剂量组雄性大鼠RBC、HCT、RDW均低于对照组、高剂量组雄性大鼠RBC、HGB、HCT低于对照组,RDW低于对照组,其差异均有统计学意义。结论肟草酮原药的无明显损害作用剂量为:雄性大鼠(9.67±0.65)mg/(kg·d),雌性大鼠(10.21±0.45)mg/(kg·d)。     

二烯丙基三硫90d经口染毒对Wistar大鼠的亚慢性毒性作用

目的研究二烯丙基三硫(Diallyl Trisulfide,DATS)对Wistar大鼠的亚慢性毒性作用。方法 SPF级Wistar大鼠80只,按体重随机分为玉米油对照组、DATS低(30 mg/kg)、中(60 mg/kg)、高(90 mg/kg)剂量组每组20只,雌雄各半。连续灌胃染毒90 d,实验结束后,处死大鼠,检测血常规、血清生化和脏器系数等,并观察病理改变。结果雄性DATS低、中、高剂量组白细胞数均高于对照组(P0.05),高剂量组血小板高于对照组(P0.05);雌性低、高剂量组白细胞高于对照组(P0.05);雄性DATS中、高剂量组肝脏系数高于对照组(P0.05),高剂量组脾脏系数高于对照组(P0.05),中剂量组肾脏系数高于对照组(P0.05),雌性DATS染毒组肝脏系数、肾脏系数高于对照组(P0.01,P0.05),肉眼观察雌雄大鼠均出现组肝、脾、肾增大,颜色变深,病理切片雌雄中、高剂量组肾脏、脾脏出现明显病理学改变。结论 DATS经口染毒可引起大鼠白细胞升高和肝、脾肿大,高剂量DATS对大鼠肝、脾可能有一定毒性。     

全氟辛烷磺酸对SD大鼠肝毒性及其肝脏细胞色素P450 mRNA表达的影响

目的研究全氟辛烷磺酸盐(PFOS)染毒SD大鼠后,其对大鼠肝脏毒性及细胞色素P450(CYP450)亚型mRNA表达的影响。方法 40只SD雄性大鼠,随机分为5组:4个PFOS染毒组,染毒剂量分别为0.5、1.0、3.0和10.0mg/(kg.d),1个对照组。连续灌胃染毒28 d后,分析血清生化指标和观察肝脏病理变化,并检测肝脏CYP450各亚型mRNA的表达水平。结果与对照组相比,大鼠染毒PFOS 28 d后,各染毒组大鼠的体重明显降低,10.0 mg/kg染毒组大鼠的肝脏重量显著增加。各染毒组大鼠的血清谷丙转氨酶、胆汁酸等水平显著升高,三酰甘油、总胆固醇含量降低。病理检查发现,各染毒组大鼠的肝脏细胞出现浊肿、变性,甚至坏死。此外,3.0和10.0 mg/kg组大鼠肝脏的CYP1A2mRNA水平降低,而CYP17A1 mRNA水平升高。各染毒组CYP2B1 mRNA水平均升高,呈剂量效应关系。结论 PFOS的肝毒性呈剂量效应关系,并对CYP450的各个亚型有不同影响。     

28d灌胃给予氯化甲基汞对Wistar雌性大鼠免疫系统影响的研究

目的研究氯化甲基汞对雌性大鼠免疫系统的影响。方法将Wistar雌性大鼠随机分为3组:分别灌胃给予0(对照组)、0.75(低剂量组)和1.5(高剂量组)mg/(kg·BW)氯化甲基汞,连续进行28 d。实验结束后,取血并处死实验动物,对脏器称重计算脏器系数,并进行全血和脾淋巴细胞分型、Con A诱导淋巴细胞转化实验以及抗体生成细胞检测(PFC)等相关免疫检测。结果 0.75和1.5 mg/(kg·BW)组与对照组比较,肝脏系数均降低,肾脏系数均升高;全血淋巴细胞分型中,1.50 mg/(kg·BW)组CD4/CD8的比值降低,B细胞的比例升高;脾淋巴细胞分型中0.75 mg/(kg·BW)组B细胞比例降低,1.50 mg/(kg·BW)组CD4/CD8细胞比值降低、NK细胞比例升高;0.75和1.50 mg/(kg·BW)组PFC检测结果显著降低。结论经口28 d连续给予一定剂量氯化甲基汞可对雌性大鼠产生免疫毒性作用。     

90d喂养氟磺唑草胺原药对大鼠毒性作用的研究

目的研究长期低剂量摄入氟磺唑草胺原药对大鼠的毒性作用,确定其最大无作用剂量,为安全生产及慢性毒性实验提供剂量参考。方法依据氟磺唑草胺原药急性经口LD50的1/125、1/25和1/5将80只SD大鼠,雌雄各半,按体重随机分为4组,分别为氟磺唑草胺原药11.76 mg/kg·bw·d组、58.80 mg/kg·bw·d组、294.00 mg/kg·bw·d和正常对照组。在90 d喂养结束后隔夜禁食并处死实验大鼠,同时检测血液学、血清生化、体重和脏器系数等指标,并对结果进行统计学处理。结果氟磺唑草胺原药引起雄性大鼠高剂量组的ALT、ALP、TBIL和BUN明显高于对照组,高剂量组的CHOL及中、高剂量组的TG明显低于对照组,雌性大鼠高剂量组的TP、ALB、CHE明显低于对照组,高剂量组雄、雌性大鼠WBC明显高于对照组,高剂量组雄、雌性大鼠RBC明显低于对照组,中、高剂量组雄性大鼠和高剂量组雌性大鼠HGB明显低于对照组,高剂量组雌性大鼠白细胞分类中淋巴细胞明显高于对照组、中性粒细胞明显低于对照组,雄性大鼠高剂量组脑、心、肺、肝、睾丸及中、高剂量组脾、肾的脏体比系数明显高于对照组,雌性大鼠高剂量组心、脾及中、高剂量组脑、肺的脏体比系数明显高于对照组(P<0.05,P<0.01)。结论氟磺唑草胺原药对雄、雌性大鼠经口亚慢性染毒剂量为58.80 mg/kg·bw·d及以上时,对大鼠有毒性效应;90 d喂养氟磺唑草胺原药对大鼠最大无作用剂量为11.76 mg/kg·bw·d。     

四溴双酚A对环青春期雄性大鼠的毒性研究

目的初步探讨四溴双酚A对环青春期雄性大鼠的毒性影响。方法基于环青春期雄性SD大鼠模型,将19 d龄雄性大鼠随机分为4组:对照、低、中和高剂量组,四溴双酚A掺入饲料给予,染毒剂量分别为0、2、6和18 mg/kg·bw,每组15只,连续暴露31 d,实验期间观察并记录大鼠包皮分离时间,实验结束后测各项血液学、临床生化指标以及激素水平,进行脏器称重以及病理组织学检查。结果受试物各剂量组大鼠体质量、包皮分离时间,以及激素水平与对照组比较,差异无统计学意义;高剂量组提肛肌-球海绵体肌系数、脾脏重量和脾脏系数,以及各剂量组甲状腺系数较对照组明显下降(P0.05);血常规检测结果显示低、高剂量组白细胞计数和淋巴细胞计数,高剂量组嗜碱性粒细胞比率、单核细胞计数和嗜碱性粒细胞计数,以及各剂量组未成熟网织红细胞指数较对照组明显下降(P0.05);血生化检测结果显示中、高剂量组间接胆红素较对照组明显升高(P0.05),各剂量组总胆汁酸较对照组明显下降(P0.05),上述差异均有统计学意义。肝、肾、脾、睾丸和甲状腺病理指标未显示有受试物引起的异常改变。结论四溴双酚A对环青春期雄性大鼠肝脏、脾脏、造血系统和甲状腺有影响。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.