Changes in inflammatory factors and protein expression in sulfur mustard(1LD50)-induced pulmonary in- jury in rats / 实用医学杂志

Objective To establish an animal model of SM by equal toxicity dose(1LD50)-induced acute pulmonary injury in rats and compare the differences of inflammatory factor and protein expression. Methods Rats were randomly divided into five groups. ELISA and immunohistochemical methods were measured. Results Serum INF-γ and IL-23 levels in the intraperitoneal SM group were increased compared with the tracheal SM group;there were also significant differences in serum IL-4 levels between the two groups. In the alveolar septum , the positive expression ratios of NF-Kβ1,NF-Kβp65,ERK,JNK,and p38MAPK in the intraperitoneal SM group were increased compared with the tracheal SM group. Conclusion Using SM (1LD50),There are significantly higher serum inflammatory factor levels and protein-related expression in the alveolar septum of rats intraperitoneally injected with SM compared with those administered SM by intratracheal instillation. The results suggest that pulmonary inflammatory reactions associated with SM are dependent on the route of exposure.

Morphological assessment of sulfur mustard-induced acute lung injury in rats through different routes / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells.</p><p><b>METHODS</b>One hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy.</p><p><b>RESULTS</b>In the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeⅡalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05).</p><p><b>CONCLUSION</b>The lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups.</p>

Decontamination properties of nanoscale metal oxides against chemical warfare agents / 国际药学研究杂志

Objective To elevated the decontam ination properties of commercial nanoscale metal oxides against chemical warfare agents (CWA), and provide more foundation for the satisfactory materials of CWA decontamination. Methods Some nanocrystals of commercial metal oxides such an MgO, TiO2, ZnO and zinc nickel ferrite compound had been chosen to compare their decontamination properties. The nanocrystals were mixed with three representative compounds, sulfur mustard (HD), soman (GD) and S-(2-diisopropylaminoethyl) O-ethyl methylphosphonothioate (VX) at room temperature and natural light. The analogous experiments were conducted without addition of nanocrystals as negative control. After a fixed time, the samples were then analyzed by the methods of T-135, Schoeneman reaction and conversion method to determine the content of CWA. The decontamination properties of nanocrystals were compared with negative control. Results The chosen nanoscale metal oxides excepted nanoscale MgO had good decontamination properties against HD, and they all could decontaminate GD quickly. Nanoscale TiO2 had superior decontamination properties against GD and HD. At the room temperature and natural light, HD was completely decontaminated within 20 hours and GD was completely decontaminated within 4 hours by nanoscale TiO2. The nanocrystals of metal oxides didn′t decontaminate VX effectively. Compared to the activated clay group, nanoscale MgO had superior decontamination properties against VX over other nanocrystals (P<0.05), but the percentage of degradation was lower than 20% within 7 h. Conclusion The chosen nanoscale TiO2 has superior decontamination properties against GD and HD than others in natural condition, but it isn′t a promising agent for the decontamination of VX.

Mechanisms of lung injuries exposed to sulfur mustard:recent advances / 中国药理学与毒理学杂志

Sulphur mustard (SM) is a corrosive alkylating agent that is likely to be absorbed in vivo through the lungs,eyes and skin into internal organs. SM not only can produce its peculiar cytotoxic?ity thought to be mediated by the alkylation of DNA,protein and nucleic acids,but is a strong mutagen and carcinogen. However,whatever the way SM poisoning occurs,lungs are the most vulnerable, and early death is mainly carused by both the acute respiratory distress syndrome and pulmonary infec?tion. In this review,we analyzed SM-induced lung injury mechanisms.

Generation of cytochrome P-450 CYP3A65 labeled fluorescence transgenic zebrafish and its biological response to environmental pollutants / 中国药理学与毒理学杂志

OBJECTlVE To establish Tg(-6.3CYP3A65∶EGFP) transgenic zebrafish for quick, intuitive detection of heavy metals ( copper, cadmium and zinc) , dioxin-like PCBs ( PCB126) and other environmental pollutants. METHODS Tol2 transposon system was used to generate transgenic zebrafish lines Tg(-6.3CYP3A65∶EGFP) in which CYP3A65 promoter regualated labeled fluorescence. The effect of heavy mentals ( copper, cadmium and zinc ) and PCB126 on the relative amounts of CYP3A65 gene expression was determined by observing the change in fluorescence intensity. RESULTS The relative gene expression of CYP3A65 was significantly increased after 96 h exposure to copper 0.1 and 0.2μmol·L-1 , cadmium 0.35 and 0.7μmol·L-1 , zinc 1.5 and 3μmol·L-1 , and PCB126 2-32μmol·L-1 , respectively ( P<0.01) , but decreased after 96 h exposure to copper 0. 9 μmol·L-1 , cadmium 2. 7 and 5.4 μmol·L-1 , and zinc 24μmol·L-1 , respectively( P<0.01) . CYP3A65 gene expression was significantly increased after 168 h exposure to copper 0.1 and 0.2 μmol·L-1 , cadmium 0.35 and 0.7 μmol·L-1 , zinc 1.5 and 3 μmol·L-1, and PCB126 2-32 μmol·L-1, respectively(P<0.01), but decreased after 168 h exposure to copper 0.9 μmol·L-1, cadmium 2.7 and 5.4 μmol·L-1, and zinc 12 and 24 μmol·L-1( P<0.05) , in a concentration-dependent manner. CONCLUSlON The results suggest that zebrafish CYP3A65 gene expression and the CYP3A65 labeled fluorescence lines can be another candidate biomarker for detecting environmental pollutants.

Developmental toxicity of muscone on zebrafish embryos / 中国药理学与毒理学杂志

OBJECTIVE To investigate the develop mental toxicity of muscone to embryos. METHODS With zebrafish embryos as a model,The 3 h post fertilization (hpf)embryos were exposed to muscone at 5,10,20,40,80 and 160 μmol·L -1 culture solutions for 96 h and inspected daily with mi-croscopy for larval morphology.The drug solution was replaced every 24 h.Spontaneous move ments were checked at 24 hpf.Heart rate at 48 hpf,hatching rate,e mbryo deformity rate and mortality rate were evaluated.The expression of sepn1 was determined with real-ti me quantitative PCR technique at 96 hpf.RESULTS The 24 hpf spontaneous move ments showed no significant difference.At 48 hpf, spine curvature,pericardial ede ma,yolk sac ede ma,and abnormal swi mming were observed.In addition, the 48 hpf heart beats(10 s)was decreased fro m 26.5 ±1 .0 to 18.0 ±1 .9(P <0.01 ).At 48 hpf , hatching rate of 5 ~40 μmol·L -1 decreased(P <0.05),while of 160 μmol·L -1 increased (P <0.05) co mpared with muscone 0 μmol·L -1 .Muscone had little effect on hatching rate at other ti me points;Mal-formation rate and mortality rate at higher concentrations were up to 100%.The sepn1 gene expression at 96 hpf in the exposure groups decreased co mpared with that of control group(P <0.01 ).CONCLU-SION Muscone had toxic effects on the develop ment of zebrafish embryos,including spine curvature, abnormal swi mming,and pericardial ede ma.These effects may be related to the inhibition of sepn1 gene expression by muscone.