Chelation in Metal Intoxication XXXVIII: Effect of Structurally Different Chelating Agents in Treatment of Nickel Intoxication in Rat

Some structurally different chelating agents viz. -mercapto-ß-(2-furyl)acrylic acid (MFA), -mercapto-ß-(2-thienyl) acrylicacid (MTA), meso 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercap-topropane-1-sulfonate(DMPS), diethyl dithiocarbamate (DE-DTC), and N-benzyl-D-glucaminedithiocarbamate (NBG-DTC) were evaluated for their efficacyto mobilize nickel and reverse some nickel-induced biochemicalalterations in experimental nickel intoxication. MFA, DMSA,and NBG-DTC appear more effective than their corresponding homologs,MTA, DMPS and DE-DTC, respectively, in enhancing urinary andfecal excretion of nickel and lowering tissue burden of nickelin nickel preexposed rats. These, particularly NBG-DTC, appearpromising in the treatment of nickel (II) poisoning. However,there seems no definite relationship between the structure ofthe chelating agents examined and their ability to counteractthe effects of nickel.     

Effectiveness of Chelation Therapy with Time after Acute Uranium Intoxication

Effectiveness of Chelation Therapy with Time after Acute UraniumIntoxication. DOMINGO, J. L, ORTEGA, A., LLOBET, J. M., ANDCORBELLA, J. (1990). Fundam. Appl. Toxicol 14, 88–95.The effect of increasing the time interval between acute uraniumexposure and chelation therapy was studied in male Swiss mice.Gallic acid, 4,5-dihydroxy-l,3-benzenedisulfonicacid (Tiron),diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylicacid (5-AS) were administered ip at 0,0.25, 1,4, and 24 hr aftersc injection of 10 mg/kg of uranyl acetate dihydrate. Chelatingagents were given at doses equal to one-fourth of their respectiveLD50 values. Daily elimination of uranium into urine and feceswas determined for 4 days after which time the mice were killed,and the concentration of uranium was measured in kidney, spleen,and bone. The excretion of uranium was especially rapid in thefirst 24 hr. Treatment with Tiron or gallic acid at 0, 0.25,or 1 hr after uranium exposure significantly increased the totalexcretion of the metal. In kidney and bone, only administrationof Tiron at 0,0.25, or I hr after uranium injection, or gallicacid at 1 hr after uranium exposure significantly reduced tissueuranium concentrations. Treatment at later times (4 to 24 hr)did not increase the total excretion of the metal and did notdecrease the tissue uranium concentrations 4 days after uranylacetate administration. The results show that the length oftime before initiating chelation therapy for acute uranium intoxicationgreatly influences the effectiveness of this therapy.     

Effects of Detergent Formula Chelating Agents on the Metabolism and Toxicity of Cadmium in Mice

Abstract Chelating agents like NTA (nitrilotriacetic acid) STPP (sodiumtripolyphosphate, Na₅P₃O₁₀) and EDTA (ethylenediaminetetraacetic acid) are used as components of detergents. An increased toxicity of some metal compounds when combined with NTA has led to decreased use of this chelating agent in relation to STPP. In the present studies short-term and long-term effects of these chelating agents on cadmium toxicity in mice were investigated. I: In the short-term study, mice subcutaneously exposed to CdCl₂ (3.2 mg Cd/kg b.wt.) in combination with STPP (32 mg/kg b.wt.) demonstrated a markedly higher mortality compared to animals given CdCl₂ alone. This increase in mortality was similar to the one encountered when CdCl₂ (3.2 mg Cd/kg b.wt.) and NTA (32 mg/kg b.wt.) were combined. Animals exposed subcutaneously to CdCl₂ + STPP or CdCl₂ + NTA showed histological evidence of liver necrosis 24 hrs after exposure not seen in animals given the same dose of CdCl₂ alone and also had markedly lower cadmium concentrations in the livers compared to only Cd-exposed animals. II: In the long-term study, mice were exposed orally to CdSO₄ (50 p.p.m. Cd) alone or in combination with STPP (500 p.p.m.), NTA (500 p.p.m.) or EDTA (50 p.p.m.) by continuous administration via the drinking water for 18 months. A decreased total excretion of urine proteins was seen in all Cd- treated animals irrespectively of the combination with various chelating agents. The conclusion of the present work was that NTA and STPP given by subcutaneous injection to mice markedly increased the toxicity of cadmium but that neither NTA, STPP nor EDTA given orally altered the toxicity of cadmium during a period of long-term exposure of 18 months.     

万古霉素用药时间对小鼠肾脏及转运体的影响

目的:探讨万古霉素(VCM)用药时间与小鼠肾毒性的相关性及其作用机制.方法:选取25只雄性C57BL/6小鼠随机分为VCM给药(600 mg/kg,腹腔注射,qd)1 d组、3 d组、7 d组、10 d组和空白对照组(生理盐水)各5只.末次给药后24 h,称取小鼠肾脏质量;采用全自动生化分析仪检测小鼠血清肌酐、尿素氮含...     

四种络合剂对小鼠体内170^Tm促排效果的比较

应用小鼠对四种络合剂的~(170)Tm内污染促排效果进行了比较性研究。结果表明,~(170)Tm内污染后,立即给促排剂400μM/kg,Ca-DTPA效果最好;在延迟给促排剂情况下,Zn-DTPA与Ca-DTPA等效,且优于811(喹胺酸)和EDTA。     

Ricin: Mechanism of Action,Detection, and Intoxication

Abstract

The many uses of ricin for basic research and clinical studies have made it an intensively studied molecule. Although the exact mechanism by which the toxin kills animals is unknown, ricin kills cells by entering the cytosol and inhibiting protein synthesis. In all areas of clinical use, forensic medicine, and basic scientific inquiry, the capability to detect the toxin is of primary importance. Recent efforts to produce a vaccine originate from a perception that this widely available toxic plant protein could be a poor man's weapon of mass destruction.     

海藻多糖对小鼠抗微生物药理作用的实验研究

目的:考察了海藻多糖多次给药(14~17 d)对小鼠抗微生物能力的影响。方法:取雄性昆明种小鼠,按体质量随机分为8组,分别为空白对照组、正常对照组、模型组、紫芝多糖1 000 mg/kg、海藻多糖125、250、500和1 000 mg/kg剂量组,每组12只动物,每天早8:00禁食,下午2:00根据其体质量灌胃给药,用量体积为0.4 mL/20 g,空白组不给药和溶媒,正常和模型组给予同体积的0.5%的CMC液,给药2 h后按3 g/只动物的量给食,共给药15 d,于给药第6天除空白和正常对照组外其余所有小鼠皮下一次注射环磷酰胺100 mg/kg造模,末次给药24 h后小鼠眼眶取血,分离血清测定其抑菌圈,试验结果用采用统计学处理。结果:用海藻多糖125、250、500和1 000 mg/kg经口灌胃后,能明显增大环磷酰胺所致免疫低下和荷瘤S180瘤小鼠血清的抑菌能力,用海藻多糖250、500和1 000 mg/kg经口灌胃后,能明显增加经放射损伤小鼠血清的抑菌能力;用海藻多糖500 mg/kg灌胃小鼠感染绿脓假单胞菌后72 h内死亡率明显下降;海藻多糖对金黄色葡萄球菌感染小鼠有明显的保护作用;用海藻多糖500 mg/kg剂量能明显减少小鼠感染流感病毒后的死亡率。结论:由此可见,海藻多糖可以通过提高免疫而产生一定的抵抗细菌和病毒感染的能力。     

去甲斑蝥酸钠对肝癌小鼠模型不同时间给药的不良反应比较

目的研究去甲斑蝥酸钠在不同时间段给药对于肝癌小鼠模型的不良反应的差别。方法固定剂量去甲斑蝥酸钠在2 am,10 am,6 pm 3个不同时间连续给药10 d,治疗肝癌荷瘤小鼠,比较各组不良反应的差异。结果去甲斑蝥酸钠不同时间给药,其不良反应有差异,以2 am给药组不良反应最轻,6 pm给药组不良反应最严重。结论去甲斑蝥酸钠治疗肝癌小鼠模型的不良反应与给药时间有一定关系。     

去甲斑蝥酸钠对肝癌小鼠模型不同时间给药的不良反应比较

目的 研究去甲斑蝥酸钠在不同时间段给药对于肝癌小鼠模型的不良反应的差别.方法 固定剂量去甲斑蝥酸钠在2 am,10 am,6 pm 3个不同时间连续给药10 d,治疗肝癌荷瘤小鼠,比较各组不良反应的差异.结果 去甲斑蝥酸钠不同时间给药,其不良反应有差异,以2 am给药组不良反应最轻,6 pm给药组不良反应最严重.结论 ...     

Aluminium Distribution and Excretion: A Comparative Study of a Number of Chelating Agents in Rats

Abstract: The present study was conducted to assess in rats the comparative effects of a number of chelating agents on the urinary excretion and tissue distribution of Al. Adult male Spraguc–Dawley rats received a single intraperitoneal dose of aluminium (Al) nitrate nonahydrate (0.24 mmol/kg). Ten min. after Al injection, l,2–dimethyl–3–hydroxypirid–4–one, 2,3–dihydroxybenzoic acid, picolinic acid, methylmalonic acid, ethylenediamine–di(o–hydroxyphenylacetic) acid, 1–benzyl–2–methyl–3–hydroxypyrid–4–one, l–(p–methylbenzyl)–2–methyl–3–hydroxypyrid–4–one, l–(p–methoxy–benzyl)–2–methyl–3–hydroxypyrid–4–one, 1 –(p–chlorobenzyl)–2–methyl–3–hydroxypyrid–4–one, 1–benzyl–2–ethyl–3–hydroxypyrid–4–one, 1–(p–methylbenzyl)–2–ethyl–3–hydroxypyrid–4–one, l–[3–hydroxy–2–methyl–4–oxopyridy]]–2–ethanesulfonic acid and l–benzyl–(4–carboxylic acid)–3–hydroxy–2–methyI–4–oxopyridine were given by gavage at 1.79 mmol/kg. A control group received similar volumes of distilled water. An additional group of rats received a subcutaneous injection of desferrioxamine at 1.79 mmol/ kg. Urine samples were collected daily for three consecutive days and the animals were killed after this period. Samples of brain, bone, liver, kidney and spleen were collected. Although desferrioxamine, l,2–dimethyl–3–hydroxypirid–4–one, 1–(p–methylbenzyl)–2–methyl–3–hydroxypyrid–4–one, l–(p–methoxybenzyl)–2–methyl–3– hydroxypyrid–4–one. l–(p–methylbenzyI)–2–elhyl–3–hydroxypyrid–4–one, l–[3–hydroxy–2–methyl–4–oxopyridyl]–2–ethanesulfonic acid and l–benzyl–(4–carboxylic acid)–3–hydroxy–2–methyl–4–oxopyridine significantly enhanced the total excretion of Al into urine, only treatment with 1–(p–chlorobenzyl)–2–methyl–3–hydroxypyrid–4– one and l–benzyl–2–ethyl–3–hydroxypyrid–4–one significantly reduced Al concentrations in all analyzed tissues. No beneficial effects of the remaining chelators on Al mobilization were observed. Further studies on the effects of some 3–hydoxrypyrid–4–ones on Al removal can be of interest for the treatment of Al accumulation and toxicity.     

The Effect of Ethanol on the Duration of Toxic Action of Lidocaine: An Experimental Study on Rats and Mice

Abstract The purpose of this study was to determine whether previous acute or subchronic administration of ethanol would alter the toxicity of lidocaine in experimental animals. The principal method used was the measurement of the duration of the narcosis-like state produced by lidocaine (intraperitoneally) in rats. The concentration of ethanol in the blood of rats was at a maximum about one hour after the administration by gastric intubation. Ethanol in doses of 1.5–3 g/kg, given 1–3 hours previously, caused a significant prolongation of lidocaine narcosis. This prolongation was not due to hypothermia, which occurred in animals at ordinary room temperature. The lethal action of intravenously injected lidocaine in mice was not changed by acute ethanol administration. Lidocaine narcosis was shortened by subchronic ethanol administration but this shortening was statistically significant only when ethanol was given continuously to rats in their drinking fluid. Hence it remains to be shown, for instance, what role the inhibition or induction of drug-metabolizing enzymes by ethanol plays in the prolongation or shortening of lidocaine narcosis.     

止血药的分类和临床合理使用

目的了解止血药的作用分类和临床使用注意事项,为其合理使用提供综合信息.方法将临床常用的止血药按作用机理进行分类和归纳,并比较不同药物的作用特点和使用方法.结果与结论不同止血药的止血作用机理差别很大,临床使用时应掌握适应证,避免不合理使用而引起不良反应.     

口服异氟烷、七氟烷对小鼠的麻醉作用观察

目的:观察口服异氟烷(Iso)、七氟烷(Sev)对小鼠的镇痛及催眠等麻醉作用。方法:按分层随机设计,将180只小鼠分为18组(n=10),分别用于热板实验、扭体实验(各60只):对照组(生理盐水(NS)组),Iso1、Iso2、Iso3组(1、2、3mL·kg-1),Sev1、Sev2组(5、10mL·kg-1)。催眠实验(60只):对照组(NS组),Iso1、Iso2、Iso3组(6、8、10mL·kg-1),Sev1、Sev2组(20、40mL·kg-1)。小鼠Iso、Sev灌胃后用热板和扭体实验观察小鼠热板痛阈值(HPPT)和扭体次数的变化情况,以评估镇痛作用;用催眠实验的睡眠时间变化情况评估催眠作用。结果:与对照组比较,Iso(1～3mL·kg-1)、Sev(5、10mL·kg-1)灌胃能增加HPPT值,减少扭体次数(P<0.05,P<0.01);Iso(6～10mL·kg-1)、Sev(20、40mL·kg-1)灌胃后能延长睡眠时间(P<0.01)。结论:在本实验条件下,小鼠Iso、Sev灌胃可产生有效的催眠和镇痛等麻醉作用。     

Amelioration of Metal-Induced Toxicity in Caenorhabditis elegans: Utility of Chelating Agents in the Bioremediation of Metals

The presence of toxic amounts of transition metals in the environment may originate from a range of human activities and natural processes. One method for the removal of toxic levels of metals is through chelation by small molecules. However, chelation is not synonymous with detoxification and may not affect the bioavailability of the metal. To test the bioavailability of chelated metals in vivo, the effects of several metal/chelator combinations were tested in the environmentally relevant organism Caenorhabditis elegans. The effect of metal exposure on nematode growth was used to determine the toxicity of cadmium, copper, nickel, and zinc. The restoration of growth to levels observed in nonexposed nematodes was used to determine the protective effects of the polydentate chelators: acetohydroxamic acid (AHA), cyclam, cysteine, calcium EDTA, desferrioxamine B, 1,2-dimethyl,3-hydroxy,4-pyridinone, and histidine. Cadmium toxicity was removed only by EDTA; copper toxicity was removed by all of the chelators except AHA; nickel toxicity was removed by cyclam, EDTA, and histidine; and zinc toxicity was removed by only EDTA. These results demonstrate the utility of polydentate chelators in the remediation of metal-contaminated systems. They also demonstrate that although the application of a chelator to metal contaminants may be effective, binding alone cannot be used to predict the level of remediation. Remediation depends on a number of factors, including metal complex speciation in the environment.     

Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning

Abrin is a highly toxic protein obtained from the seeds of the rosary pea plant Abrus precatorius, and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The major clinical manifestations following pulmonary exposure to these toxins consist of severe lung inflammation and consequent respiratory insufficiency. Despite the high similarity between abrin and ricin in terms of disease progression, the ability to protect mice against these toxins by postexposure antibody-mediated treatment differs significantly, with a markedly higher level of protection achieved against abrin intoxication. In this study, we conducted an in-depth comparison between the kinetics of in vivo abrin and ricin intoxication in a murine model. The data demonstrated differential binding of abrin and ricin to the parenchymal cells of the lungs. Accordingly, toxin-mediated injury to the nonhematopoietic compartment was shown to be markedly lower in the case of abrin intoxication. Thus, profiling of alveolar epithelial cells demonstrated that although toxin-induced damage was restricted to alveolar epithelial type II cells following abrin intoxication, as previously reported for ricin, it was less pronounced. Furthermore, unlike following ricin intoxication, no direct damage was detected in the lung endothelial cell population following abrin exposure. Reduced impairment of intercellular junction molecules following abrin intoxication was detected as well. In contrast, similar damage to the endothelial surface glycocalyx layer was observed for the two toxins. We assume that the reduced damage to the lung stroma, which maintains a higher level of tissue integrity following pulmonary exposure to abrin compared to ricin, contributes to the high efficiency of the anti-abrin antibody treatment at late time points after exposure.     

Influence of Lichenin and Pectin on Mice During Chronic Intoxication with Cadmium(II) Chloride

Pharmaceutical Chemistry Journal - Lichenin from thalli of Flavocetraria cucullata and pectin from vegetative mass of Amaranthus retroflexus were isolated. Their monomeric compositions were...     

The Behavioral Effects of Perinatal Methimazole Administration in Swiss Webster Mice

The Behavioral Effects of Perinatal Methimazole Administrationin Swiss Webster Mice. RICE, S. A., MILLAN, D. P., AND WEST,J. A. (1987). Fundam. Appl. Toxicol. 8, 531–540. Methimazolewas tested for use as a positive control agent in behavioralstudies of mice. Continuous administration of the antithyroidagent via drinking water (0.1 mg/ml) from Day 16 of pregnancythrough Day 10 postpartum produced developmental delays in miceoffspring. Ten methimazole and 12 untreated litters were studied.Developmental milestones were unaltered; i.e., time of pinnadetachment, incisor eruption, eye opening, vaginal patency,and testicular descent were not different between groups. Meanbody weights of methimazole offspring were consistently reduced,but significant differences were isolated to a few days in thepreweaning period and a few weeks during the postweaning period.There was no enduring effect. All preweaning tests showed somesignificant treatment-related changes; methimazole pups weredevelopmentally delayed. Surface righting time was increasedwhile time pivoting and the number of quadrants traveled weredecreased in methimazole pups. Negative geotaxis showed significanttreatment-related increases in the time to orient 180° uphill,the percentage of pups orienting 180° uphill, and the percentageof pups orienting <180°. Ontogeny of swimming abilityalso showed significant delays. The only postweaning test evaluated,time on a rotating rod, showed no treatment-related effects.Brain weights Postnatal Day (PND) 120 were not different betweengroups. In this study, methimazole produced developmental delaysin mice that were detectable by behavioral tests. Thus, methimazolehas potential as a positive control agent for mice, not onlyto validate preweaning test sensitivity, but also to validatea laboratory's ability to perform preweaning behavioral studies.     

Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents

Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species.     

锌、金属硫蛋白、超氧化物岐化酶对镉中毒拮抗作用的比较

本研究用CdCl_2制备小鼠镉中毒模型,使发生明显的脂质过氧化损伤,锌、金属硫蛋白和超氧化物岐化酶分别预处理后,可降低中毒鼠死亡率,肝、肾组织中丙二醛含量明显降低,金属硫蛋白含量明显升高,肝组织中锌/铜比例升高。提示锌、金属硫蛋白和超氧化物岐化酶能拮抗镉引起的致死作用和脂质过氧化作用。