乙苯亚慢性吸入染毒大鼠肝毒性效应的研究

目的观察亚慢性吸入染毒乙苯对大鼠肝组织的氧化应激损伤。方法将40只健康3周龄SPF级Sprague-Dawley雄性大鼠随机分为4组,分别为对照(新鲜空气)组和低(433.5 mg/m3)、中(4 335 mg/m3)和高(6 500 mg/m3)剂量乙苯染毒组,每组10只。大鼠以笼养方式放入HOPE-MED 8050A型动式染毒柜内,采用吸入方式进行染毒,每天6 h,每周5 d,连续染毒13周。用Beutler改良法测定肝组织还原型谷胱甘肽(GSH)含量,用TBA比色法测定肝组织丙二醛(MDA)含量,在常规显微镜和超微显微镜下观察肝组织结构变化。结果与对照组相比,各剂量乙苯染毒组大鼠肝组织MDA含量升高,GSH含量均降低,差异有统计学意义(P<0.05)。且随着乙苯染毒剂量的升高,大鼠肝组织MDA含量呈上升趋势,GSH含量呈下降趋势。乙苯染毒大鼠肝组织出现肿胀、坏死、部分组织溶解等病理变化;肝细胞呈现核皱缩、线粒体空泡等凋亡形态学特征。结论亚慢性吸入染毒乙苯可诱导大鼠肝组织氧化损伤和细胞凋亡。     

Comparison of blood toluene levels after inhalation and oral administration

The purpose of this investigation was to compare blood toluene levels in Sprague-Dawley rats after oral and inhalation administration. Groups of 30 rats were dosed by gavage with 86.7, 217, 433, or 867 mg toluene/kg body wt or exposed for up to 6 hr, 5 rats per exposure, to an atmosphere of either 200 or 1000 ppm toluene. Blood was sampled by cardiac puncture from 5 rats in each of the six dose groups at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hr after gavage dosing or the beginning of the inhalation exposure. Blood toluene levels were analyzed. A four-parameter model was fitted to the blood toluene levels of the orally dosed rats. The area under the curve generated by this model, representing total blood toluene concentration over 6 hr, was calculated and compared to the area under the blood toluene curve for the 6-hr inhalation exposure. Integrated areas from the two routes of exposure were used for direct comparison of oral and inhalation exposures. The data demonstrate that gavage dosing can be used to approximate inhalation exposure to toluene.     

甲苯二异氰酸酯亚慢性吸入染毒对大鼠肝脏的影响

将40只健康3周龄SPF级Sprague-Dawley雄性大鼠随机分为4组(对照组及染毒低、中、高剂量组),每组10只。大鼠以笼养方式放入HOPE-MED 8050A型动式染毒柜内,各剂量组分别以3.06、12.25、49.00 mg/m3剂量的甲苯二异氰酸酯(TDI)吸入染毒,对照组予新鲜空气处理,6 h/d,5 d/周,连续染毒13周。末次染毒后进行肝功能及氧化损伤指标的测定。在常规和超微显微镜下观察肝组织结构变化。与对照组相比,各剂量组大鼠血清生化酶中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和γ-谷氨酰基转移酶(GGT)均有不同程度的升高,碱性磷酸酶(ALP)有所降低,差异均有统计学意义(P0.05);各剂量组大鼠肝组织丙二醛(MDA)含量升高,还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)含量均降低,差异有统计学意义(P 0.05)。与对照组相比,TDI染毒大鼠肝组织出现肿胀、坏死、部分组织溶解等病理变化;肝细胞呈现核皱缩、线粒体空泡等凋亡形态学特征。提示亚慢性吸入染毒TDI可诱导大鼠肝组织氧化损伤和细胞凋亡。     

戒除吸入性甲苯成瘾滥用精神药物1例报告

甲苯是一种成瘾性化学剂,频繁暴露于甲苯会使个体产生异常的适应耐受性,突然戒断后会出现相关精神神经症状,为甲苯成瘾的临床标志。甲苯的过量或慢性吸入可造成身体各系统的伤害,因此,应提高对甲苯神经毒性和成瘾性的认识。本文对1例为戒除甲苯成瘾而滥用精神药物导致严重不良反应病例的临床表现及救治进行分析。     

Absence of carcinogenic activity in Fischer rats and B6C3F1 mice following 103-week inhalation exposures to toluene

Toluene, methylbenzene, is used to back-blend gasoline, as a chemical intermediate, and as a solvent; more than 7 million tonnes are produced each year in the United States. Following 14-15-week toxicity studies to estimate appropriate exposure concentrations for the carcinogenesis bioassays, toxicology and carcinogenesis studies of toluene (>99% pure) were conducted by whole-body inhalation exposures of F344/N rats and B6C3F1 mice of each sex for 15 months or two years. Toluene levels were 0 (chamber controls), 600, and 1,200 ppm for rats and 0, 120, 600, and 1200 ppm for mice. Exposures were 6.5 hr/day 5 days/wk. Genetic toxicology studies using Salmonella typhimurium, mouse L5178Y lymphoma cells, and Chinese hamster ovary cells were negative. No chemically related neoplasm was found in male rats, and one nasal, two kidney, and two forestomach neoplasms observed in female rats were considered not to be associated with the toluene exposure. For mice, no biologically important increase was observed for any nonneoplastic or neoplastic lesion. Studies by others had reported carcinogenicity of toluene, especially for total malignant tumors.     

Provocation of respiratory allergy in guinea pigs following inhalation of free toluene diisocyanate

An animal exposure experiment which simulated a workplace exposure situation was made to compare toluene diisocyanate (TDI) concentrations which resulted in antibody production with those which elicited pulmonary responses. Groups of guinea pigs were exposed to inhaled TDI from 0.02 to 1.0 ppm (g/g) for 3 h/day on 5 consecutive days. Three weeks later the animals were challenged with 0.02 ppm of free TDI for 15 min. TDI specific antibodies and pulmonary responses were evaluated. Specific antibody production showed a linear correlation to TDI concentration at induction. Most of the animals exposed to TDI levels above 0.2 ppm displayed significant pulmonary responses, but no correlation was found between TDI concentration at induction and the intensity of pulmonary response upon challenge to free TDI. These results indicated that there was a threshold concentration of 0.02 ppm TDI for antibody production and for the development of pulmonary response. It was also found that exposure to TDI at a level lower than its threshold concentration for sensitization may elicit a response in previously sensitized individuals.     

Differences following skin or inhalation exposure in the absorption and excretion kinetics of trichloroethylene and toluene.

The concentrations of trichloroethylene in breath and blood and the urinary excretion of its metabolites following 30 minutes' direct immersion of one hand in the liquid, were compared with those obtained after four hours' inhalation exposure to the vapour of 100 ppm, described in a previous paper. The comparison shows that the end-tidal air concentrations during the first two hours of the post-exposure period were about twice as high in the case of skin exposure as in that of inhalation exposure, although the uptake of the solvent through the skin was only about one-third of the inhaled uptake. A kinetic approach suggested that differences in trichloroethylene movement in the body would be a principal cause of this discrepancy. The results of a similar series of experiments using toluene suggested that it is less readily taken up than trichloroethylene through the skin. It was concluded from the present investigation that analyses of not only breath but also of blood or urine are necessary and toluene would rarely be absorbed through the skin in toxic quantities during normal industrial use.     

Synthesis and in vivo anti-mutagenic activity of novel melatonin derivatives

Extensive literature suggests that melatonin play a role against the degenerative effect of central neurotoxins by its acting as free radical scavenger. This study aimed at evaluation of the anti-mutagenic activity of novel synthesized indole derivatives 2, 4a, and 8 in albino male mice in comparison with the parent melatonin. Efficacy of melatonin and its derivatives to influence cyclophosphamide (CP)-induced genotoxicity was tested using micronuclei (MN) formation in the bone marrow cells and determination of DNA, RNA and protein levels as well as cholinesterase and peroxidase activities in several organs of male mice. Following intragastrical injection of melatonin or one of its derivatives daily for 1 week, CP was given intraperitoneally, i.p., as a single dose of 25mg/kg BW. Pyridazin-4-yl thiadiazoloindole derivative 8, diaminothiophen-5-yl thiadiazoloindole derivative 4a and melatonin were significantly able to reduce the number of micronucleated polychromatic erythrocytes (MnPCEs) in the bone marrow cells induced by CP (P<0.0001, P<0.001, P<0.01, respectively). However, reduction of MN formation in the bone marrow cells was not significant when thiadiazoloindole derivative 2 was administered (P=0.14). Examination of the protective effect of melatonin and its derivatives on the levels of DNA, RNA and protein as well as enzyme activities showed that compound 8 had the ability to inhibit the clastogenic effect of CP in several organs of male mice. These findings suggest that compounds 4a, 8 and melatonin were able to reduce the mutagenicity effect of CP in male mice. The ability of compounds 4a, 8 and melatonin to reduce CP-related genotoxicity is possibly attributed to their antioxidant activity.     

微囊藻毒素肝毒性分子机制研究进展

微囊藻毒素(microcystin,MC)是淡水富营养化水体最常见的一类藻类毒素。它具有嗜肝性,主要在肝脏被转运、吸收和积累。MC对肝脏的毒性作用已有大量研究,尤其是对肝毒性作用的分子机制研究。本文就MC所引起的急慢性肝毒性的分子机制的研究进展进行综述。     

The protective role of fruits and vegetables against radiation-induced cancer

The role of fruits and vegetables in protecting against radiation-induced cancer and the positive evidence from epidemiology and ancillary investigations are discussed in this review. The recently reported Hiroshima and Nagasaki atomic bomb survivor studies provide strong evidence for the protective role of fruits and vegetables against radiation-induced cancer. The anticarcinogenic substances contained in, and the anticarcinogenic mechanisms proposed for, fruits and vegetables are reviewed. The anticarcinogenic effectiveness of fruits and vegetables are compared with that of dietary supplements. The reasons for the observed superiority of fruits and vegetables are advanced.     

保护性因素在自杀防护中的作用

自杀是“一个人有意识地企图伤害自己的身体、以达到结束自己生命的行为”,对社会、家庭和自身安全产生了极大危害,已成为全球各国普遍关注的社会和公共卫生问题。1999年Mann等提出自杀的应激-易感模型,认为自杀是应激因素、保护性因素（包括家庭、社会、文化等因素）与个体素质（包括易感性、人格、认知等因素）三者之间相互影响的过程。     

Chronic intermittent toluene inhalation initiated during adolescence in rats does not alter voluntary consumption of ethanol in adulthood

Voluntary inhalation of organic solvents, such as toluene, is particularly prevalent in adolescent populations and is considered to be a contributing factor to substance use and dependence later in life. While inhalants are often the initial “drug” experienced during this period, alcohol is another substance readily abused by adolescent populations. Although both substances are thought to have similar actions within the brain, our understanding of the implications of adolescent inhalant abuse upon subsequent exposure to alcohol remains to be investigated. Thus, this study aimed to assess locomotor responses to acute ethanol and voluntary ethanol consumption following a period of toluene inhalation throughout adolescence/early adulthood. Adolescent male Wistar rats (postnatal day [PN] 27) inhaled air or toluene (3000 ppm) for 1 h/day, 3 days/week for 4 (PN 27–52) or 8 weeks (PN 27–80) to mimic the patterns observed in human inhalant abusers. Following the exposure period, cross-sensitization to acute ethanol challenge (0.5 g/kg, intra-peritoneally [i.p.]), and voluntary consumption of 20% ethanol in a chronic intermittent 2-bottle choice paradigm, were assessed. Hepatic ethanol and acetaldehyde metabolism and liver histopathology were also investigated. Chronic intermittent toluene (CIT) exposure throughout adolescence for up to 8 weeks did not alter the behavioral response to acute ethanol or voluntary consumption of ethanol in adulthood, although an age-dependent effect on ethanol consumption was observed (p < 0.05). Both liver function and pathology did not differ between treatment groups. Thus, in the paradigm employed, CIT exposure throughout adolescence and early adulthood did not predispose rats to subsequent locomotor sensitivity or voluntary consumption of ethanol in adulthood.