DMPS对大鼠脑汞含量影响的研究

给大鼠每次腹腔注射０．５ｍｇＨｇ／ｋｇ氯化汞共４０次后，治疗组大鼠分别给予１、２、３或４次腹腔注射ＤＭＰＳ，每次注射剂量为０．２７ｍｍｏｌ／ｋｇ。对照组大鼠则于相同时间注射生理盐水。最后一次注射后２４小时处死大鼠，测定脑和肾汞含量。结果表明ＤＭＰＳ治疗显著降低肾汞含量，但脑汞含量无明显变化。提示ＤＭＰＳ治疗汞中毒不能引起汞的体内重新分布，不能增加大鼠脑汞含量。     

硒多糖、亚硒酸钠对大鼠血硒浓度和肝细胞色素P_(450)单加氧酶系的影响

研究了一次和连续７天腹腔注射硒多糖、亚硒酸钠对大鼠血硒浓度及肝细胞色素Ｐ４５０、ｂ５、ＮＡＤ（Ｐ）Ｈ－细胞色素Ｃ还原酶、谷胱甘肽硫转移酶（ＧＳＴ）和谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）的影响；并比较了硒多糖与亚硒酸钠的作用。结果表明：一次腹腔注射Ｓｅ０．６ｍｇ／ｋｇ体重的硒多糖和亚硒酸钠后，血硒浓度迅速增加，在注射后２小时血硒浓度达到高峰，随后血硒浓度逐渐下降。亚硒酸钠在大鼠体内的吸收和排出均较硒多糖快。连续７天腹腔注射０．２ｍｇ／ｋｇ体重剂量硒多糖和亚硒酸钠后，硒多糖和亚硒酸钠组大鼠血硒浓度分别为对照组的２．６倍和２．１倍，其中硒多糖组的血硒含量显著高于亚硒酸钠组（Ｐ＜０．０５）；硒多糖和亚硒酸钠在体内、外均降低肝细胞色素Ｐ４５０、ｂ５的含量，抑制ＧＳＴ的活性，硒多糖的作用尤为显著，分别为对照组的５７％、７０％和６２％（Ｐ＜０．０５）。两种硒化合物对ＮＡＤ（Ｐ）Ｈ－细胞色素Ｃ还原酶无明显影响。硒多糖和亚硒酸钠均能显著增强ＧＳＨ－Ｐｘ的活性（Ｐ＜０．０５）。     

硒、镉对小鼠大脑脂质过氧化作用的交互影响

昆明种雄鼠７０只，体重１８～２４ｇ，随机分为５组，每天分别给予腹腔注射０．０５、０．１０ｍｇ／ｋｇ硒，０．２３ｍｇ／ｋｇ镉，０．１０ｍｇ／ｋｇ硒＋０．２３ｍｇ／ｋｇ镉，对照组给予等体积的生理盐水，实验期５０天。末次注射２４ｈ后断头取脑，分离脑区（小脑、脑桥、四叠体、丘脑、皮质），加０．２５ｍｏｌ／Ｌ蔗糖制匀浆，取上清液测定ＧＳＨ和ＭＤＡ含量。结果显示，各组脑组织ＧＳＨ含量都呈降低趋势，单纯镉组脑组织ＭＤＡ含量显著增高，硒具有降低镉致脂质过氧化代谢产物生成增加的作用，但其自身也可使脑组织的ＧＳＨ消耗增加。     

920对MAPO诱发的小白鼠骨髓细胞微核率的抑制作用

ＭＡＰＯ是一种强诱变剂，可以显著引起小白鼠骨髓细胞微核率升高。９２０是一种枸杞多糖提取物。研究结果表明：以９２０（２００ｍｇ／ｋｇ）每天灌胃１次连续５天，第５天灌胃后分别腹腔注射ＭＡＰＯ（２．５、５、１０、２０和４０ｍｇ／ｋｇ），微核抑制率在２２．３～４４．３％之间；９２０（１２．５～２００ｍｇ／ｋｇ）每天灌胃１次连续５天，第５天灌胃后腹腔注射１次ＭＡＰＯ（１０ｍｇ／ｍｇ），２４ｈ后处死动物制片，     

用计算机辅助精子分析系统测定TCDD对大鼠精子运动能力的影响

利用计算机辅助的精子分析系统（ＣＡＳＡ）研究了２,３,７,８—四氯二苯－Ｐ－二口恶口英（ＴＣＤＤ）对大鼠精子运动能力的影响。给２１天龄幼鼠腹腔注射ＴＣＤＤ０．１、１．０和５．０μｇ／ｋｇ,对照组注射等量体积的溶媒。在性成熟后（９０天）,用扩散法收集附睾尾精子,测定其运行速度（ＶＣＬ、ＶＳＬ、ＶＡＰ）、运动方式（ＳＴＲ、ＬＩＮ、ＢＣＦ、ＡＬＨ、ＭＡＤ等）及活动精子的比率（Ｍｏｔ％）。结果表明,ＴＣＤＤ１．０μｇ／ｋｇ组,精子的运动速度明显低于对照组（ＶＣＬＰ＜０．０５;ＶＡＰ、ＶＳＬ、ＢＣＦＰ＜０．０１）,０．５μｇ／ｋｇ时精子的运动速度、及前向性和直线性运动性能均明显降低（Ｐ＜０．０１）,活动精子的比率也明显低于对照组（Ｐ＜０．０１）。本研究结果为ＴＣＤＤ的男性生殖毒理学研究,以及ＣＡＳＡ在男性生殖毒理学研究中的应用提供了进一步参考依据     

甘草甜素和齐墩果酸对大鼠镉中毒性肝损伤的防护作用与机理

为探讨甘草甜素（ＧＬ）和齐墩果酸（ＯＡ）对大鼠镉中毒性肝损伤的防护作用及其作用机理,给大鼠腹腔注射ＣｄＣｌ２溶液（０．８ｍｇＣｄ＾２＋／ｋｇ体重）,两组染镉大鼠分别同时皮下注射ＧＬ的生理盐水溶液（２０ｍｇ／ｋｇ,每周３次）和ＯＡ的吐温－生理盐水混悬液（６０ｍｇ／ｋｇ,每周５次）,测定血清转氨酶、肝镉（Ｃｄ）、金属硫蛋白（ＭＴ）含量,检查肝组织病理形态学。结果显示：ＧＬ和ＯＡ延缓、降低了镉引起的血清     

新型螯合剂对镍致小鼠肝脏毒性的影响

为寻找镍（Ｎｉ）中毒的新型解毒剂，给小鼠腹腔注射氯化镍溶液（含镍５ｍｇ／ｋｇ），３０分钟和２４小时后分别注射Ｎ－苯甲基－Ｄ－葡萄糖胺二硫代氨基甲酸钠（ＢＧＤ）及ｍｅｓｏ－２，３－二巯基琥珀酸（ＤＭＳＡ）（剂量均为４００μｍｏｌ／ｋｇ），测定各阶段肝脏脂质过氧化水平（ＬＰＯ）、血浆丙氨酸转氨酶（ＡＬＴ）活力及组织中镍、钙、铁、铜、锌等含量。结果显示：镍染毒后，各项指标的测定结果与生理盐水对照组比较，差异均有显著性（Ｐ＜０．０１）。ＢＧＤ及ＤＭＳＡ对这些变化有明显抑制。提示：新型螯合剂ＢＧＤ及ＤＭＳＡ对镍致小鼠肝脏毒性有较好的解毒作用。     

氟化钠,氯化汞和亚砷酸钠对小鼠睾丸早期精细胞微核率的影响

采用Ｔａｔｅｓ微核试验法检测３种无机化学物对雄性小鼠生殖细胞染色体的损伤作用。不同剂量的氟化钠（１４ｍｇ／ｋｇ、２８ｍｇ／ｋｇ）、氯化汞（０．５ｍｇ／ｋｇ、１．０ｍｇ／ｋｇ）和亚砷酸钠（０．２５ｍｇ／ｋｇ、０．５ｍｇ／ｋｇ）分别经腹腔注射染毒，每天１次，连续３天，于首次染毒后第１５天杀鼠。测得微核率为７．２％，１０．０‰；６．４‰、５．６‰和３．４‰、３．０‰。其中氟化钠和氯化汞组的微核率与阴性对照组（２．２‰）比较．有显著差异．可以认为是雄性生殖细胞染色体断裂剂。根据染毒到制片的间隔时间判断，氟化钠和氯化主要作用于减数分裂前的Ｇ１和Ｓ期初级精母细胞。     

甲醛染毒大鼠脂质过氧化水平分析

用不同剂量（５，１０，２０，５０，１００ｍｇ／ｋｇ）甲醛经腹腔注射染毒ＳＤ大鼠后２４小时，以及１０ｍｇ／ｋｇ染毒后２，６，２４小时收集大鼠血和肝脏。对样品的测定结果显示，红细胞ＳＯＤ活性，全血ＧＳＨ－ＰＸ活性，红细胞内谷胱甘肽含量以及血浆与肝组织ＭＤＡ浓度等五项指标与染毒剂量均有不同程度相关，其中红细胞ＳＯＤ对甲醛最为敏感，５ｍｇ／ｋｇ时就比对照组有明显降低，在时间效应关系中可以见到红细胞内ＳＯＤ     

长期低铅染毒对大鼠心肌微粒体膜脂质过氧化影响

分别以醋酸铅（ＰｂＡｃ２）１０，３０和９０ｍｇ／（ｋｇ·ｄ）给雄性ＳＤ大鼠灌胃，连续９周，结果表明心肌微粒体膜（ＭＭＳ）Ｎａ＋，Ｋ＋－ＡＴＰ酶（Ｎａ泵）、超氧化物歧化酶活性、血锌含量降低，ＭＭＳ丙二醛、血和尿铅、胸主动脉Ｃａ２＋含量及ＭＭＳＣａ２＋－ＡＴＰ酶（Ｃａ泵）活性增高，与对照组比较均呈显著性差异。离体大鼠ＭＭＳ单独与不同浓度（０．３，０．６，１．２ｍｍｏｌ／Ｌ）ＰｂＡｃ２共同温育后，除Ｃａ泵活性下降外，出现与体内同样毒性作用。结果提示小剂量ＰｂＡｃ２使ＭＭＳ酶的损害和抗氧化能力降低在铅中毒性心肌损伤中具有重要的作用     

BSO、GSH、VC和DMPS对汞肾毒性影响的实验研究

目的探讨一次染汞的肾脏毒性作用并观察2氨基4(S丁基磺酰亚氨)丁酸(BSO)、还原型谷胱甘肽(GSH)、维生素C(VC)和二巯基丙磺酸钠(DMPS)预处理对汞肾脏毒性的影响。方法Wistar大鼠64只,随机分成8组。第1组为对照组,第2～4组为低、中、高剂量染汞组,分别皮下注射0.75、1.5和2.5mg kg的氯化汞溶液,第5～8组为预处理干预组。BSO预处理组先腹腔注射BSO0.5mmol kgbw,4h后皮下注射0.75mg kgHgCl2溶液。其他3个预处理组中,先分别腹腔注射GSH3mmol kg,VC4mmol kg或DMPS200μmol kgbw,2h后皮下注射2.5mg kgHgCl2溶液。注射容量均为5ml kgbw。对照组皮下注射生理盐水。注射12h后收集大鼠12h尿液,采集血液,分离血清,切取肝脏和肾皮质样品。测定肝脏、肾皮质和尿中汞含量;尿NAG、ALP、LDH活性和尿蛋白,血清尿素氮(BUN)含量。结果染汞后肝、肾皮质和尿汞含量随染汞剂量加大而逐渐增加。肾皮质汞含量有明显的剂量-效应关系,高剂量组肝汞含量显著高于中低剂量组和对照组。中高剂量组尿汞含量显著高于对照组。BSO预处理组和单纯0.75mg kgHgCl2组比,使肝汞含量增加,肾皮质和尿汞含量降低。GSH、VC和DMPS预处理组肝汞含量显著低于单纯2.5mg kgHgCl2组。尿NAG、ALP、LDH活性和尿蛋白、BUN含量随染汞剂量加大而升高,且2.5mg kgHgCl2组显著高于对照组、0.75和1.5mg kg HgCl2组。BSO预处理组尿NAG、ALP活性和尿蛋白、BUN含量显著高于单纯0.75mg kgHgCl2组和对照组。GSH、VC和DMPS预处理组和单纯2.5mg kgHgCl2组相比,尿NAG、ALP、LDH活性和尿蛋白、BUN含量显著降低。结论随着染汞剂量增加,肝脏、肾皮质和尿汞含量也增加。BSO预处理可增强汞的肾脏毒性作用,而GSH、VC和DMPS预处理则对汞的肾脏毒性具有一定的拮抗作用。     

Mobilization of mercury by DMPS in occupationally exposed workers and in model experiments on rats: evaluation of body burden

The aim of the study was to evaluate the efficacy of DMPS (sodium-2,3-dimercapto-1-propane sulfonate) (Dimaval) administration for mobilizing mercury from the body in occupationally exposed people and experimental animals. Two doses of DMPS were administered at a 24-h interval to: (a) groups of people occupationally exposed to merkury--workers of the chloralkali industry (n = 43), and dentists (n = 12), (b) non-exposed individuals (n = 20), and (c) rats chronically exposed to mercury vapour at the concentration of 0.8 mg/m3 Hg degree (6 h/day, 5 days/week) for 15 weeks. In an out-patient mobilizing test, the urinary excretion of mercury 48 h after the administration of the first dose reached 1513 micrograms in the group of industrial workers, 132.6 micrograms in dentists, and 3.78 micrograms in controls. In rats, two consecutive doses of DMPS decreased kidney content of mercury by about 30% and 50% after oral and intraperitoneal administration, respectively. Kidney mercury burden was calculated on the basis of the data from animal and human studies of the mobilization of mercury via urine after DMPS treatment: 61, 2800 and 28,000 ng/g in controls, dentists and workers, respectively. It was estimated that two doses of DMPS mobilized 17-20% (after oral administration) and 25-30% (after intramuscular administration) of kidney mercury burden, both in the control and exposed subjects.     

Effects of BSO, GSH, Vit-C and DMPS on the nephrotoxicity of mercury

OBJECTIVE: To study the effects of BSO, GSH, Vit-C and DMPS on the nephrotoxicity of mercury. METHODS: The rats in groups 1, 2 and 3 were sc injected with 0.75, 1.5 and 2.5 mg/kg HgCl2, respectively. Fourth group rats were ip injected with 0.5 mmol/kg BSO and 4h later sc administrated with 0.75 mg/kg HgCl2. The rats in groups 5, 6 and 7 were ip injected with 3 mmol/kg GSH, 4 mmol/kg Vit-C, 200 micromol/kg DMPS, respectively, and 2 h later sc administrated with 2.5 mg/kg HgCl2. Eighth group rats were sc injected with saline as a control. Mercury concentrations in the liver, renal cortex and urine, urinary NAG, ALP, LDH activities, protein and BUN contents were determined. RESULTS: Urinary NAG, ALP activities, protein and BUN contents in the rats of BSO pretreatment group were significantly higher than that of 0.75 mg/kg HgCl2 alone group and control group. As compared with 2.5 mg/kg HgCl2 alone group, urinary NAG, ALP, LDH activities, urinary protein and BUN contents decreased significantly. CONCLUSION: BSO pretreatment could enhance the renal toxicity of mercury and GSH, Vit-C and DMPS pretreatment had antagonistic effects on nephrotoxicity of mercury.     

Evaluation of the protective activity of 2,3-dimercaptopropanol and sodium 2,3-dimercaptopropane-1-sulfonate on methylmercury-induced developmental toxicity in mice

The embryotoxic and teratogenic effects of methylmercury in experimental animals have been established by several investigators. The protective activity of 2,3-dimercaptopropanol (BAL) and sodium 2,3-dimercaptopropane-1-sulfonate (DMPS, a chelator used in the treatment of inorganic and organic mercury) on methylmercury chloride (MMC)-induced maternal and developmental toxicity in mice has been evaluated in the present study. BAL and DMPS were administered subcutaneously or by gavage to pregnant mice immediately after a single oral administration of 30 mg MMC/kg given on day 10 of gestation and at 24, 48, and 72 h thereafter. Amelioration by BAL and DMPS of MMC embryo/fetotoxicity was assessed at 15, 30, and 60 mg/kg/day and at 90, 180, and 350 mg/kg/day, respectively. Treatment with BAL did not ameliorate the maternal toxicity or the developmental toxicity of MMC observed in the mouse. In contrast, DMPS at 90, 180, and 360 mg/kg/day significantly reduced the maternal lethality of MMC, whereas treatment with 180 and 360 mg DMPS/kg/day showed significant protective activity against MMC-induced embryotoxicity and teratogenicity. Based on the present findings, DMPS might be a useful chelator against the maternal and developmental toxicity induced by methylmercury.     

D-青霉胺和二巯基丙磺酸钠对急性汞氧化损伤的影响

目的 研究预投D-青霉胺(DPA)和二巯基丙磺酸钠(DMPS)对急性汞氧化损伤的保护作用,进一步探讨无机汞氧化损伤的作用机制。方法 48只Wistar大鼠随机分成6组。第1组以5ml／kg皮下注射0．9％氯化钠溶液,第2～4组分别皮下注射0．75,1．5,2．5mg／kgHgCl2溶液。第5,6组大鼠分别腹腔注射DMPS、DPA200μmol／kg,2h后再投与2．5mg／kg HgCl2溶液。染毒12h后,收集12h尿样,测定尿汞含量。染毒48h后。切取肾脏和肝脏,测定丙二醛(MDA)和谷胱甘肽(GSH)含量及谷胱甘肽过氧化物酶(GSH-Px)活力。结果DMPS可显著降低肾脏MDA含量,而DPA对肾脏MDA含量没有影响。DMPS和DPA对肝脏MDA的变化没有影响。DMPS和DPA两干预组在肾脏和肝脏中GSH含量和GSH-Px活力都明显高于2．5mg／kg染汞组,差异有显著性。DPA能显著降低肾脏汞的含量。结论 DMPS可显著减轻汞在肾脏的氧化损伤,但对肝脏没有影响。DPA对汞在肾脏和肝脏氧化反应都没有影响。DMPS能减少肾脏和肝脏GSH的耗竭,而给予DPA只能防止肾脏GSH的耗竭,对肝脏GSH影响不大。DMPS和DPA能防止GSH-Px耗竭。DPA可减少汞在肾脏的蓄积量,致使汞分布到其他组织器官中,而DMPS不能引起汞的这种分布。     

Organ and subcellular distribution of cadmium in rats exposed to cadmium, mercury, and selenium

Four groups of rats were given: cadmium chloride (Cd), cadmium chloride and mercuric chloride (Cd + Hg), cadmium chloride and sodium selenite (Cd + Se), or cadmium chloride, mercuric chloride, and sodium selenite (Cd + Hg + Se). All animals received subcutaneous doses of 115mCdCl2 (0.3 mg Cd/kg) every other day for 2 weeks. Mercuric chloride was administered intravenously at doses of 0.5 mg Hg/kg every other day, and Na2 75SeO3 intragastrically at doses of 0.1 mg Se/kg every day for a fortnight. The whole-body and organ retention of cadmium changed slightly with the type of exposure. A significant interaction effect of the examined elements was noted in the nuclear and soluble fractions of the liver and kidneys. Mercury decreased the cadmium concentration in both the nuclear and soluble fractions of the kidneys and diminished the effect of selenium on the cadmium level in the soluble fraction of the kidneys. In the liver the presence of mercury contrary to selenium, lowered the cadmium level in the nuclear fraction. The pattern of cadmium binding to proteins of the soluble fraction of the kidneys and liver remained the same in all groups of animals.     

The permeability of the Syrian hamster placenta to mercury

Three mercury compounds; mercuric acetate, mercuric nitrate and phenylmercuric acetate, labeled with ²⁰³Hg, were administered to pregnant hamsters early on the 8th gestation day. Mercury levels of selected tissues were measured 24 and 96 hours after injection. Significant concentrations of mercury were found in maternal tissues, placentae, and embryos. The results are discussed in relation to other reports on the placental transfer of radiolabeled cadmium, manganese, mercury, and zinc.     

Influence of mercuric chloride on the metabolism and hepatotoxicity of bromobenzene in rats

When male Sprague-Dawley rats were treated with 1 mg mercuric chloride (HgCl2)/kg, sc 6 hr prior to or simultaneously with a single 2.5-mmole/kg ip dose of bromobenzene and sacrificed 48 hr after the bromobenzene dose, the activities of serum transaminases (SGOT and SGPT) were found to be significantly reduced when compared with those obtained in bromobenzene-alone-treated rats. Similar phenomena were observed when rats were treated simultaneously with 1 or 2 mg HgCl2/kg and 1 mmole bromobenzene/kg, but not when bromobenzene was given 6 hr prior to HgCl2 injection. When 5 mmole bromobenzene/kg and 1 mg HgCl2/kg were given simultaneously to the animals, such an apparent reduction in bromobenzene toxicity was again observed. In each case, HgCl2 alone had no effect on the transaminase activities. HgCl2 (1 mg/kg, sc) treatment reduced the hepatic microsomal cytochrome P-450 content. Treatment with 1 mg HgCl2/kg 6 hr prior to bromobenzene injection (2.5 mmole/kg) significantly reduced the urinary excretion of para- and metabromophenols, and parabromocatechol during 0 to 24-hr period without affecting the urinary thioethers. These data suggest a possible reduction in the rate of formation of bromobenzene epoxide intermediate due to mercury pretreatment, resulting in a lowering of the steady state level of this epoxide so that an inhibition of hepatotoxicity due to bromobenzene could occur. However, simultaneous treatments of HgCl2 and bromobenzene failed to modify the urinary metabolic excretion pattern of bromobenzene. When rats were given 10, 50, and 100 ppm of HgCl2 in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmole bromobenzene/kg and were sacrificed 48 hr after the dose, no changes in SGOT and SGPT activities were observed. These results indicate that changes in the metabolism and hepatotoxicity of bromobenzene due to mercury depend on (a) the dose and time of mercury administration, and (b) the mode of administration of mercury, acute or chronic.     

竹荪多糖早期和晚期干预对砷中毒大鼠肝功能的影响

目的探讨砷致肝损伤大鼠体内砷含量和肝功能受竹荪多糖干预的影响。方法 108只成年清洁级SD大鼠随机分为正常对照组(24只,以普通饲料喂饲)、砷+竹荪同时干预组[(简称同时干预组),24只,10 mg/ml的竹荪多糖每日20ml/kg灌胃,且饲料中砷含量为50 mg/kg]、砷染毒组(60只,喂饲砷含量50 mg/kg的饲料),均雌雄各半。采用喂饲法进行染毒3个月后,以HE、Masson染色观察肝损伤情况。继续将砷染毒组随机均分为砷染毒组、砷+二巯基丙磺酸钠(DMPS)组[(简称DMPS组),每天以5 mg/kg二巯基丙磺酸钠腹腔注射,连续3 d,间隔4 d为一个周期]、砷+竹荪后干预组[(简称竹荪后干预组),10 mg/ml竹荪多糖每日20 ml/kg灌胃],每组18只,雌雄各半,三组均以砷含量为50 mg/kg的饲料喂饲,各组再处理3个月,观察大鼠体内砷含量和肝功能的变化情况。结果肝脏HE、Masson染色显示,与正常对照组比较,同时干预组、砷染毒组光镜下肝组织均有不同程度肝损伤出现。与正常对照组相比,各处理组大鼠血清ALT和AST的活力升高,且随着染毒时间的增加,各组大鼠血清ALT和AST的活力呈上升趋势。与正常对照组相比,各处理组大鼠血、尿、肝脏砷含量均增高(P0.05)。与砷染毒组相比,同时干预组、DMPS组、竹荪后干预组肝砷降低,血砷和尿砷升高(P0.05)。与DMPS组相比,同时干预组肝砷先降低后升高,尿砷先升高后减低,血砷先升高后减低再升高(P0.05)。与同时干预组相比,竹荪后干预组肝砷升高,血砷、尿砷降低(P0.05)。与竹荪后干预组相比,DMPS组肝砷降低,尿砷升高,血砷先升高后降低(P0.05)。结论竹荪多糖早期干预能减轻砷中毒大鼠肝损伤程度,且竹荪在砷中毒早期干预对肝损伤的减轻效果优于砷中毒后再干预,但竹荪多糖对砷中毒大鼠体内驱砷效果仍不及二巯基丙磺酸钠。