亚慢性染毒2,3,7,8-四氯二苯并二噁英(TCDD)对大鼠血清中氧化应激指标的影响

目的 研究2,3,7,8-四氯二苯并二(噁)英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)对大鼠血清中氧化应激指标的影响.方法 清洁级Wistar雄性大鼠32只,体重(100±10)g,随机分成4组,连续经口染毒TCDD 90 d,剂量分别为2.5、25、250 ng/kg,对照组给予二甲基亚砜(DMSO),测定SOD、CuZn-SOD、Mn-SOD、GSH-Px、GST活性及MDA的含量.结果 TCDD染毒90 d后,与对照组相比,各染毒组雄性大鼠血清中MDA含量明显增高(P＜0.05);各染毒组总SOD、CuZn-SOD、MnSOD、GSH-Px活力均有所下降,其中除CuZn-SOD外,与对照组相比差异均有统计学意义(P＜0.05).同时各染毒组GST活力显著增加,且各组间差异有统计学意义(P＜0.05).结论 亚慢性染毒引起MDA含量增加,大鼠血清中抗氧化指标出现异常改变,提示体内出现氧化与抗氧化系统失衡.     

亚慢性染毒2,3,7,8-四氯二苯并二(噁)英(TCDD)对大鼠血清维生素A、E的影响

目的了解亚慢性暴露于2，3，7，8-四氯二苯并二噁英（TCDD）对Wistar大鼠血清维生素A、E水平的影响。方法将64只实验Wistar大鼠按雌、雄随机分为染毒高（250ng／kg）、中（25ng／ks）、低（2．5ng／kg）剂量和空白对照共4组，每组8只，经口染毒。90d后对实验大鼠股动脉取血，离心后取上层血清，用无水乙醇沉淀蛋白，加环己烷萃取后，使用荧光分光光度仪在不同波长下测定其荧光值，计算出维生素A、E浓度，进行统计分析。结果与对照组比较，TCDD染毒大鼠血清维生素A和维生素E的平均水平降低，差别具有统计学意义（P〈0．05）。结论在实验条件下，TCDD亚慢性暴露可以对Wistar大鼠血清维生素A与维生素E的质量浓度水平有一定影响。     

2,3,7,8-四氯二苯-p-二(口恶)英对雌性小鼠血浆维生素A、E的影响

目的了解2,3,7,8-四氯二苯-p-二(口恶)英(TCDD)对雌鼠血浆维生素A、E水平的影响.方法将实验昆明种雌性小鼠24只,随机分为染毒高(100 μg/kg)、中(10 μg/kg)、低(1 μg/kg)剂量和空白对照4组,腹腔注射染毒.48 h后对实验小鼠取血,离心后取上层血浆,用无水乙醇沉淀蛋白,加环己烷萃取后,使用荧光分光光度仪在不同波长下测定其荧光值,计算出维生素A、E浓度,进行统计分析.结果对照及染毒剂量低、中、高4组中小鼠血浆维生素A的平均水平差异无显著性(P＞0.05);血浆维生素E的平均水平差异有显著性(P＜0.05),对照组与低剂量组之间维生素E的浓度水平差异无显著性,但与中、高剂量组之间维生素E的浓度水平差异都有显著性(P＜0.05).结论在此实验条件下,尚不能够认为TCDD对雌鼠血浆维生素A的水平有影响,但对维生素E的水平有一定影响.     

亚慢性染毒2,3,7,8-四氯二苯并二(口恶)英对雄性大鼠生殖系统的影响

目的 了解2,3,7,8-四氯二苯并二(口恶)英(TCDD)对雄性大鼠生殖系统的影响.方法 清洁级Wistar雄性大鼠32只,体重(100±10)g,随机分成4组,每组8只,连续经口灌胃染毒90d,剂量分别为2.5,25,250 ng/kg,对照组给予二甲基亚砜(DMSO),测定血清中睾酮(T)、促黄体生成素(LH)、促卵泡生成素(FSH)的激素水平以及睾丸、前列腺、精囊腺的脏器质量系数,附睾尾精子畸形率.结果 与对照组比较,各染毒组T水平下降,差异有显著性(P＜0.05);各染毒组FSH和LH水平上升,但差异无显著性(P＞0.05);中、高剂量组的睾丸、精囊腺及所有染毒组的前列腺脏器质量系数均低于对照组(P＜0.05);各染毒组精子畸形率随剂量的增加而上升,中、高剂量组与对照组相比差异显著(P＜0.01).结论 TCDD亚慢性染毒,可影响精子和生殖系统的正常发育,并在一定程度上对生殖激素的稳态造成了干扰.     

2,3,7,8-四氯二苯-p-二英对雌性小鼠血浆维生素A、E的影响

目的了解2,3,7,8-四氯二苯-p-二(口恶)英(TCDD)对雌鼠血浆维生素A、E水平的影响.方法将实验昆明种雌性小鼠24只,随机分为染毒高(100 μg/kg)、中(10 μg/kg)、低(1 μg/kg)剂量和空白对照4组,腹腔注射染毒.48 h后对实验小鼠取血,离心后取上层血浆,用无水乙醇沉淀蛋白,加环己烷萃取后,使用荧光分光光度仪在不同波长下测定其荧光值,计算出维生素A、E浓度,进行统计分析.结果对照及染毒剂量低、中、高4组中小鼠血浆维生素A的平均水平差异无显著性(P＞0.05);血浆维生素E的平均水平差异有显著性(P＜0.05),对照组与低剂量组之间维生素E的浓度水平差异无显著性,但与中、高剂量组之间维生素E的浓度水平差异都有显著性(P＜0.05).结论在此实验条件下,尚不能够认为TCDD对雌鼠血浆维生素A的水平有影响,但对维生素E的水平有一定影响.     

哺乳期暴露2,3,7,8-四氯二苯并-p-二(噁)英的子代小鼠生殖发育以及肺组织CYP1A1水平

目的 探讨哺乳期暴露2,3,7,8-四氯二苯并-P-二(噁)英(TCDD)对子代小鼠生长发育及细胞色素P4501A1(CYP1A1)表达的影响.方法 采用清洁级昆明小鼠,设40μg/kg和20μg/kg TCDD染毒组,并分设相应的两个溶剂对照组及-个动物空白对照组.每组母鼠3只,仔鼠25～28只.母鼠分娩后的第1、3、5天腹腔注射TCDD,子代小鼠通过乳汁暴露于TCDD.观察不同生长期仔鼠的体重改变和生殖系统发育等.仔鼠生后第35天被处死,采用免疫组化法分析肺组织CYP1A1的表达.结果 TCDD染毒组的仔鼠体重明显降低,雌性仔鼠的阴道平均开放时间明显缩短,雄性仔鼠的睾丸平均下降时间明显延长.TCDD染毒组的肺泡结构紊乱,炎症细胞浸润,肺泡壁增厚水肿,CYP1A1表达量明显升高,并且雌性仔鼠的肺组织反应比雄性仔鼠严重.而对照组中雌雄间差异没有显著性.结论 单一哺乳期暴露于TCDD可使子代小鼠体重下降,雌性仔鼠性成熟提前,雄性仔鼠性成熟延缓.仔鼠肺组织CYP1A1表达明显增加,并存在性别差异.     

亚慢性接触2,3,7,8-四氯二苯-并-二(口恶)英对成年雄性大鼠海马形态结构的影响

目的 研究亚慢性低剂量2,3,7,8-四氯二苯-并-二(口恶)英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)染毒对SD雄性成年大鼠海马形态结构的影响.方法 将32只1月龄SPF级Sprague-Dawley雄性大鼠随机分为4组,分别为对照(玉米油)组和低(2 ng/kg)、中(1...     

亚慢性染毒2,3,7,8-四氯二苯并二噁英对雄性大鼠生殖系统的影响

目的了解2,3,7,8-四氯二苯并二噁英(TCDD)对雄性大鼠生殖系统的影响。方法清洁级Wistar雄性大鼠32只,体重(100±10)g,随机分成4组,每组8只,连续经口灌胃染毒90 d,剂量分别为2.5,25,250 ng/kg,对照组给予二甲基亚砜(DMSO),测定血清中睾酮(T)、促黄体生成素(LH)、促卵泡生成素(FSH)的激素水平以及睾丸、前列腺、精囊腺的脏器质量系数,附睾尾精子畸形率。结果与对照组比较,各染毒组T水平下降,差异有显著性(P<0.05);各染毒组FSH和LH水平上升,但差异无显著性(P>0.05);中、高剂量组的睾丸、精囊腺及所有染毒组的前列腺脏器质量系数均低于对照组(P<0.05);各染毒组精子畸形率随剂量的增加而上升,中、高剂量组与对照组相比差异显著(P<0.01)。结论TCDD亚慢性染毒,可影响精子和生殖系统的正常发育,并在一定程度上对生殖激素的稳态造成了干扰。     

2,3,7,8-四氯二苯-p-二噁英对雌性小鼠血浆维生素A、E的影响

了解 2 ,3 ,7,8 四氯二苯 p 二英 (TCDD)对雌鼠血浆维生素A、E水平的影响。方法　将实验昆明种雌性小鼠 2 4只 ,随机分为染毒高 ( 10 0 μg/kg)、中 ( 10 μg/kg)、低 ( 1μg/kg)剂量和空白对照 4组 ,腹腔注射染毒。 48h后对实验小鼠取血 ,离心后取上层血浆 ,用无水乙醇沉淀蛋白 ,加环己烷萃取后 ,使用荧光分光光度仪在不同波长下测定其荧光值 ,计算出维生素A、E浓度 ,进行统计分析。结果　对照及染毒剂量低、中、高 4组中小鼠血浆维生素A的平均水平差异无显著性 (P >0 0 5 ) ;血浆维生素E的平均水平差异有显著性 (P <0 0 5 ) ,对照组与低剂量组之间维生素E的浓度水平差异无显著性 ,但与中、高剂量组之间维生素E的浓度水平差异都有显著性 (P <0 0 5 )。结论　在此实验条件下 ,尚不能够认为TCDD对雌鼠血浆维生素A的水平有影响 ,但对维生素E的水平有一定影响     

Peripheral neuropathy after occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Reports of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) describe signs and symptoms consistent with exposure-related peripheral neuropathy. In a crosssectional study, prevalence of peripheral neuropathy was measured in 265 workers exposed 15 years earlier to chemicals contaminated with TCDD and in 244 unexposed, age-, race-, gender- and community-matched comparisons. Cases of peripheral neuropathy were defined from examination, electrophysiologic and quantitative sensory tests, and symptoms. Exposure was assessed by measuring lipid-adjusted serum TCDD levels. The mean serum TCDD level for workers (220 parts per trillion (ppt)) was significantly higher than for referents (7 ppt) (p < .0001). Thirty-two percent of both worker and referent groups met the case definition for peripheral neuropathy. In the logistic regression analyses, serum TCDD level was not related to peripheral neuropathy. These data suggest that despite continued high serum TCDD levels, peripheral neuropathy is not a long-term sequela of high exposure to TCDD-contaminated chemicals. However, the study cannot preclude the occurrence and subsequent resolution of acute effects caused by high exposure, as experienced in Seveso and possibly by some workers, while exposed to high levels of TCDD-contaminated substances. © 1993 Wiley-Liss, Inc.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the lactating rat on maternal and neonatal vitamin A status

Female Sprague-Dawley rats were given a single oral dose of 10 micrograms TCDD/kg body wt after delivery. Pups were killed on postnatal day (PND) 0, 2, 4, 8, or 16. Dams and remaining weanlings were killed on PND 22 and 32, respectively. Thymus weight was lower in dams exposed to TCDD than in controls, whereas no differences in body weight or relative liver weight were found. The total amount and the concentration of vitamin A were lower in the liver but higher in the kidneys and in serum of TCDD-treated dams than in controls. TCDD-exposed weanlings showed lower weight gain, liver enlargement and thymus atrophy compared to controls. Growth reduction became more pronounced with time, liver enlargement was at its peak on PND 8 and thymus atrophy was most pronounced on PND 16, although all three effects persisted throughout the study. The total amount of vitamin A increased at a similar rate in control and TCDD-exposed weanlings throughout lactation. When the young started to eat pelleted diet there was a pronounced increase in hepatic vitamin A content. Between PND 16 and 32 controls increased their hepatic vitamin A content 21-fold, compared to 12-fold in TCDD-exposed offspring. The hepatic stores of TCDD-treated animals reached 45% of the stores of control pups on PND 32. From PND 8 renal vitamin A was significantly higher in the TCDD-exposed young than in the controls. At PND 32 TCDD-exposed weanlings had six times more renal vitamin A than controls.     

Biochemical and toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) congeners in female rats

The capability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)² and six congeners to induce toxic and biochemical changes in rats was investigated. In addition to TCDD, the following compounds were administered at a dose of 40 or 400 g/kg/day for three days P.O.: 2,7-dichlorodibenzo-p-dioxin (DCDD); 1,2,4-trichlorodibenzo-p-dioxin (TrCDD); 1,2,3,4-tetrachlorodibenzo-p-dioxin; l,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin; 3,3,4,4,5-pentachlorobiphenyl (PCB); and 2,2,4,4,5,5-hexachlorobiphenyl (HCB). Six days after treatment the animals were killed. Lipid peroxidation and glutathione peroxidase (GSH-PX) activity were determined in liver and kidney. Hepatic aryl hydrocarbon hydroxylase (AHH) activity was determined 48 hr following the administration of 400 g/kg of each congener or 40 g/kg of TCDD. With the exception of PCB and TCDD, the other congeners produced no toxic or biochemical changes at the doses given as determined by the above parameters. PCB (400 g/kg) resulted in a 4-fold increase in lipid peroxidation and a 69% decrease in GSH-PX activity. These results were comparable to the effects of a 40 g/kg dose of TCDD. PCB treatment resulted in a 80% decrease in thymus weight, and a 3.8-fold increase in AHH activity which were comparable to the effects of TCDD. A correlation appears to exist between the ability to induce hepatic AHH activity, enhance lipid peroxidation. inhibit GSH-PX activity, and decrease body and thymus weights.Abbreviations include TCDD 2,7-dichlorodibenzo-p-dioxin - DCDD 1,2,4-trichlorodibenzo-p-dioxin - TrCDD 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin - OCDD 3,3,4,4,5-pentachlorobiphenyl - PCB 2,2,4,4,5,5-hexachlorobiphenyl - HCB malondialdehyde - MDA aryl hydrocarbon hydroxylase - AHH glutathione peroxidase - GSH-PX 8-aminolevulinic acid - ALA structure-activity relations     

Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure

Presented herein are the results of follow-up examinations of 13 workers performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in a herbicide production plant. In these workers, the current mean plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high-resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid). This mean value corresponded to an estimated concentration of approximately 5,000 pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level indicates that this group was one of the most heavily exposed groups to 2,3,7,8-TCDD described in the literature. Patients with persistent chloracne had significantly higher plasma levels of 2,3,7,8-TCDD than persons without chloracne. A significant, positive correlation was found between plasma levels of 2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed since 1974. During 1996, there was a significant positive correlation between 2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides. Also in 1996, significant correlations were found between neuropsychological variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were observed between neuropsychological variables and (1) the highest levels of triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996, (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest level of cholesterol since the year 1969, and (5) cholesterol levels in 1996. Such correlations are biologically plausible, and they provide evidence of impaired cognitive performance (i.e., memory first), with a concurrent increase of plasma lipid levels. Abnormal electromyography, electroencephalography, and visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of former workers. Abnormal electroencephalography findings occurred more frequently in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p < .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the 1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was statistically significant (p < .05).     

Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

The environmental contaminant 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of highly toxic, persistent organic pollutants that accumulate in animal fat and plant tissues. Today, background TCDD levels in human fat are showing a decreasing trend. The food chain is the main source of exposure in the human population. TCDD regulates the expression of a wide range of drug-metabolizing enzymes and has an impact on a large number of biological systems. The most pronounced effects have occurred in occupational settings following the uncontrolled formation of TCDD after industrial accidents, as well as in rare intentional intoxications. Although the acute effects of TCDD exposure are well described in the literature, the long-term consequences have been underevaluated. The most well-known symptoms of severe acute intoxication are chloracne, porphyria, transient hepatotoxicity, and peripheral and central neurotoxicity. Because of the long-term persistence of TCDD in the human body, atherosclerosis, hypertension, diabetes, vascular ocular changes, and signs of neural system damage, including neuropsychological impairment, can be present several decades after massive exposure. Such chronic effects are nonspecific, multifactorial, and may be causally linked to TCDD only in heavily intoxicated subjects. This opinion is supported by the dose-dependent effect of TCDD found in exposed workers and by experimental animal studies.