三氯卡班对小鼠血浆内源性物质影响的代谢组学研究

三氯卡班被认定为一种新型的环境污染物,可能对动植物和人体产生危害,为探究三氯卡班的有害作用机制,选择C57BL6小鼠作为载体,利用分子生物学和报告基因方法考察了三氯卡班对肝脏的作用,同时利用代谢组学技术考察三氯卡班对血浆内源性代谢物变化的影响。结果表明,三氯卡班是核受体CAR的激活剂,可以提高肝脏CYP2b10的m RNA表达。同时血浆主要的内源性代谢物也产生了显著性变化,血浆中的脂肪酸比例都呈下降趋势,肉毒碱与乙酰肉碱的比例都呈上升趋势,花生四烯酸与肌酸的比例都呈上升趋势,这都与核受体CAR被激活密切相关,由此说明利用代谢组学技术能够全面地反映三氯卡班所造成的对机体的影响。     

近红外长余辉纳米颗粒经小鼠眼部暴露后体内分布和代谢情况

为了研究纳米颗粒通过眼部暴露后进入体内的路径及在体内的分布和代谢情况,实验采用近红外长余辉纳米探针作为示踪剂,对小鼠进行眼部暴露,随后利用活体成像技术观察其进入小鼠体内的过程及分布情况,于暴露第4天收集代谢产物,第7天取重要脏器和血液,并检测纳米探针的存在情况.结果显示纳米探针可由眼经口腔进入胃肠道中,并且纳米颗粒暴露4天后在小鼠的粪便中检测到强荧光信号,而尿液中的荧光信号较弱,暴露7 d后在小鼠的眼睑结膜、胃及眼球中检测到强荧光信号,而其余器官的荧光信号较弱.这表明通过眼部暴露后,纳米颗粒主要分布在眼和消化系统中,最后大部分经消化系统代谢.     

LIPID PEROXIDATION AND ANTIOXIDANT ENZYME ACTIVITY IN DIFFERENT ORGANS OF MICE EXPOSED TO LOW LEVEL OF MERCURY

The effects of mercuric chloride (Hg) on lipid peroxidation (LPO), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) levels in different organs of mice (CD-1) were evaluated. Mice were exposed (2 days/week) to 0.0 (control), 0.8 (low) and 8.0 (mid) and 80.0 (high) gHg/kg/day for 2 weeks. The high dose group was excluded from the study due to high mortality. LPO levels in kidney, testis and epididymus at low and mid doses; GR and GPx levels in testis at mid dose; SOD levels in brain and testis at both doses, liver and epididymus at mid dose; GSH levels in testis at both doses were significantly increased compared to their controls. However, the GR levels in kidney at both doses and in epididymus at mid dose; GPx levels in kidney and epididymus and SOD levels in kidney at both the doses; GSH levels in epididymus at mid dose were significantly decreased compared to their control. Body weight gain and food efficiency were significantly reduced (<0.05) in mid dose. These results indicated that Hg treatment enhanced LPO in all tissues, but showed significant enhancement only in kidney, testis and epididymus suggesting that these organs were more susceptible to Hg toxicity. The increase in antioxidant enzyme levels in testis could be a mechanism protecting the cells against reactive oxygen species.     

彗星电泳法测定双酚A对雄性幼龄小鼠脑细胞的DNA损伤

双酚A是一种日常生活中无处不在的环境雌激素,具有生殖和神经毒性,但低剂量长期暴露对发育期青少年的危害性常常被低估或忽视。本研究以4周龄雄性清洁级小鼠为实验对象,以茶油作为溶媒对照,分别以双酚A浓度为0μg·m L-1、0.1μg·m L-1、10μg·m L-1和1 000μg·m L-1的茶油灌胃小鼠8周,然后利用彗星电泳法检测各组小鼠脑细胞的DNA损伤。结果显示,不同浓度双酚A暴露8周后,彗星电泳图像显示小鼠脑细胞DNA出现不同程度的损伤,随着暴露剂量的增加,带有彗尾的脑细胞比率从对照组小鼠的9.5%分别升高到暴露组小鼠的34.5%、36.0%和50.5%,细胞总体的尾部DNA含量、尾长和尾矩也都逐渐增加,而且各双酚A暴露组小鼠与溶媒对照组小鼠脑细胞都具有显著性差异(P0.01),这说明中长期双酚A暴露(包括低浓度环境暴露)会导致雄性幼龄小鼠脑细胞的DNA损伤。     

甲醛对原癌基因c-myc、MDM2及抑癌基因p53的影响

为研究吸入性甲醛的毒性能否进入动物骨髓组织,引起骨髓组织基因表达发生改变,选择小鼠某些原癌基因和抑癌基因为研究对象,以SPF级balb/c雄性小鼠为材料,采用动态吸入方式染毒2周(5+2模式),染毒浓度分别为0, 0.5, 3.0mg/m3,用半定量RT-PCR方法检测不同浓度甲醛对小鼠染毒后骨髓组织细胞中c-myc、MDM2和p53基因表达的变化.结果表明,在不同浓度的甲醛暴露条件下,与空白对照组相比,小鼠骨髓组织中的c-myc基因,MDM2基因和p53基因表达均发生改变,在3.0mg/m3浓度组与空白对照组存在显著差异(P<0.05), c-myc基因,MDM2基因呈现表达上调,p53基因则呈现表达下调.吸入性甲醛的毒性能进入动物骨髓组织,并能引起骨髓组织基因表达发生改变.     

Effects of benzo(a)pyrene on blood components,tumor markers,and oxidative status in mice

This study was carried out to investigate the effect of long-term exposure to benzo(a)pyrene (B(a)P) in mice. Hemogram, tumor markers, oxidative status, and B(a)P residues in liver tissue were evaluated. Sixty albino Swiss mice were randomly distributed equally into three groups; the control was given 0.1?mL corn oil once a week for 8 weeks. The other two groups were given 20 and 40?mg B(a)P per kg body weight once a week orally for the same period. B(a)P-treated mice suffered from depression and ascites, and macrocytic normochromic anemia was recorded at the 16th and 30th week. There was marked leukocytosis with lymphocytosis at the early stage of the experiment, followed by leukopenia, lymphopenia, and neutropenia at the end of the experiment. Monocytes and arginase activity were elevated throughout the experiment. Alpha feto-protein was detected only in the experimental groups in the 30th week of the experiment. A marked increase in lipid peroxides associated with a decrease in reduced glutathione and glutathione-S-transferase (GST) activity was observed in liver homogenate of the B(a)P-exposed animals. Residues of B(a)P were detected in liver tissue with a concentration parallel to the B(a)P dose level. In conclusion, B(a)P caused abnormal changes in the hemogram, evidence of tumor formation through B(a)P-induced oxidative stress, and it was accumulated in the liver tissue of mice.     

Treatment and skin decontamination of sarin intoxicated mice

Abstract

This study aimed at evaluating the efficacy of oral treatment and skin decontamination with the mineral cationic carrier in sarin-intoxicated mice. Mice were contaminated with increasing percutaneous sarin doses and decontaminated. Furthermore, the surviving mice were treated per os. The behavioral patterns of the surviving animals were monitored for 72?h, including the animals’ posture, desire for food and water, and approach and touch response. The results showed the mineral cationic carrier to be capable of efficiently decontaminating animals percutaneous poisoned with triple lethal dose. The comparison of behavioral pattern of control animals against those treated per os showed statistically significant differences. Oral treatment with mineral cationic carrier may be a detoxification tool against nerve agents’ poisoning, and this merits further research.     

Toxicological effects of mouse diet contaminated with tributyltin on the immune and neurological systems of C57BL/6 mice

Organotin compounds, widely used as antifouling agents, are known to bioaccumulate in the food chain. Among organotin compounds, tributyltin (TBT), a toxic and widespread contaminant, has become a serious factor in environmental pollution and is suspected of being immunotoxic in animals. The purpose of this study was to assess the effects of 80 µg of TBT per kilogram of body weight (kg bw), provided in food, on the immune and neurological systems of C57Bl/6 mice. Data showed that TBT increased the proliferation of T and B lymphocytes in both adult and juvenile female and juvenile male mice, but that it decreased the proliferation of both T and B lymphocytes in adult male mice. The macrophages activity in female and male juvenile mice was higher than in adults of both sexes. The natural killer cytotoxic activity was also increased in juvenile and adult males and females compared to the control groups. In the brain, we observed the presence of TBT in the hippocampus, the striatum, the cortex, and the cerebellum in both the male and female groups. The highest levels were observed in the cortex of females and males, while the lowest levels were found in the cerebellum. TBT also induced an increase in the levels of the antioxidant glutathione (GSH) in the striatum, the hippocampus and in cortical structures but not in the cerebellum where the levels of TBT are lower. Our findings indicate that TBT modulated the immune and nervous systems causing endocrine and nervous perturbations.     

Biochemical evaluation of hepatotoxicity in mice due to administration of artemether

Effects of artemether administration on liver and selected biochemical parameters were evaluated. Eighty albino mice were divided into four equal groups. Group 1 was given water which served as control, while groups 2, 3, and 4 were given 1.2, 2.4, or 4.8 mg kg^?1 body weight artemether intramuscularly for five consecutive days. On day 6 all mice were sacrificed by cervical dislocation and blood was collected for analysis of alanine and aspartate transaminases, alkaline phosphatase, copper, and total proteins. Liver tissues were prepared for histological studies. It was found that the serum alanine and aspartate transaminase and alkaline phosphatase activities were higher in groups treated with artemether compared to control. The serum concentrations of copper and total proteins were lower than control. The histological features of liver tissues after administration of artemether showed histopathological alterations. These findings showed that artemether administration may have reversible adverse effects on mouse hepatocytes.     

纳米Fe3O4对小鼠肺细胞的氧化损伤

纳米Fe3O4作为一种功能材料,在生物医药、生物靶向材料、微波吸收材料和高梯度磁分离器等方面应用前景广阔,其潜在的生物毒性也备受关注。为研究纳米Fe3O4对生物体可能造成的氧化损伤,以昆明小鼠为受试体,设置5、10、20和40mg·kg-14个染毒组,腹腔注射染毒7d后,测定小鼠肺组织中活性氧(reactive oxygen species,ROS)、还原型谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)的含量。结果显示,随着纳米Fe3O4染毒剂量的升高,肺组织ROS和MDA含量逐渐上升,GSH含量逐渐降低,各指标均呈一定的剂量-效应关系。剂量≥10mg·kg-1,肺组织ROS含量与对照组相比有显著差异(p<0.05);剂量≥20mg·kg-1,肺组织MDA含量与对照组相比有显著差异(p<0.05);剂量≥40mg·kg-1,肺组织GSH含量与对照组相比有显著差异(p<0.05)。研究表明,较高剂量(≥20mg·kg-1)的纳米Fe3O4颗粒材料会引起小鼠肺细胞的氧化损伤。