Red blood cell system in albino rats exposed to long-term nitrite intoxication

The long-term intake of nitrates at a concentration of 0.2 g/l in animals affects erythrocytic parameters. The nature of this effect depends on the duration of intoxication. There are three-phase changes in the concentrations of red blood cells and hemoglobin, which accompany the substantial changes of the functional characteristics of erythrocytic membranes. The intensification of erythropoiesis developing under such conditions is based on erythroidal hyperplasia of the red bone marrow and spleen and it is of compensatory significance, by ensuring the recovery of the parameters of the erythrocytic composition by the end of the experiment.     

Impairment of humoral immune responses in mice exposed to nitrogen dioxide and ozone mixtures

The relationship between immune defense mechanisms and environmental pollutants remains unknown because of uncertainty about the effects of combined or mixed pollutants. To investigate whether exposure to toxic gas mixtures change the effect of a single gas exposure on immune function, BALB/c mice were continuously exposed to 4.0 ppm nitrogen dioxide (NO2), 0.8 ppm ozone (O3), or the mixture of NO2 plus O3 for 3, 7, 14, and 56 days. Organ weights (lung, thymus, and spleen) and antibody responses to sheep red blood cells (SRBC), and to DNP-Ficoll were measured immediately after the exposure. Lung weights in mice exposed to O3 or the mixture were increased significantly in all exposure periods. The weights of thymus and spleen in mice exposed for 3, 7, and 14 days to the mixture were decreased. O3 exposure for 56 days showed significant decreases of the weights of both organs. Antibody response to SRBC in mice exposed for 3, 7, and 14 days to O3 or the mixture was markedly suppressed, but exposure to the mixture for 56 days did not show the suppression of anti-SRBC antibody response. No differences in anti-DNP antibody response between exposed and control mice were observed, except those exposed to O3 or the mixture for 14 days. These results suggest that mixed gas exposures variously modify the effects of a single gas exposure on antibody production in mice.     

Analysis of urinary metabolites of rats exposed to ethylene oxide

Urinary metabolites of rats exposed to ethylene oxide(EO) were analyzed by gas chromatography-mass spectrometry(GC/MS). Male Wister rats(220-240 g) were exposed to EO for 6 hours. The urine was collected during 18 hours after the exposure and extracted with ethyl acetate. For the water-soluble metabolites, ethanol was added to the urine centrifuged and the supernatant fraction was evaporated to dryness. The residue of the extract was methylated with diazomethane and trimethylsilylated with bis(trimethylsilyl)trifluoroacetamide. Ethylene glycol, 2-hydroxymercapturic acid, 2-methylthioethanol and 2-mercaptoethanol were identified as the metabolites of EO. These results suggest that the inhaled EO was hydrolyzed to ethylene glycol, and conjugated with glutathion to form the mercapturic acid and methylthio metabolite.     

Changes of alveolar macrophage plasminogen activator in rats exposed to nitrogen dioxide

In order to clarify the role of nitrogen dioxide (NO2) in the development of lung injury, male Wistar rats were exposed continuously to 0.3 or 5.0 ppm NO2 for 10, 20, 30, 60 and 90 days, and alveolar macrophages and lavage fluid obtained by bronchoalveolar lavage were examined. The results were as follows: 1) The number of alveolar macrophages increased significantly in response to NO2 exposure. Throughout the whole test period, the largest number was obtained in the group exposed to 5.0 ppm, followed by the group exposed to 0.3 ppm, and then by the control group. 2) The plasminogen activator (PA) released from alveolar macrophages was increased dose-dependently by NO2 exposure. The activities were significantly high in the groups exposed for 10 to 20 days at each concentration, and then slightly decreased at 30 days. Thereafter, activity showed a tendency to increase, reaching the maximum level on the 60th day of exposure. 3) Similarly, the fibrinolytic activity in the lavage fluid was increased dose-dependently by NO2 exposure. The maximum activity was noted on the 10th day of exposure, followed by a rapid decrease up to the 30th day, and a slight rise again between the 60th and 90th day. 4) In the group exposed to 5.0 ppm NO2, total protein in the lavage fluid increased, and the elastase inhibitory capacity (EIC) per milligram of protein decreased. In the group exposed to 0.3 ppm NO2, however, no difference from the control group was noted. These results revealed that the alveolar macrophages were affected and increased PA activity as a result of exposure to as little as 0.3 ppm NO2. This was shown to result in an increase of the fibrinolytic activity in the alveoli, leading to damage to the lung tissue. This evidence may explain the morphological findings of the appearance of emphysematous change in the lungs of rats exposed to low levels of NO2. For the detection of the effect of NO2 on the lung tissue, PA appears to be a more sensitive indicator than EIC.     

Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline

Ninety-day inhalation studies were conducted on 50:50 weight percent (wt %) mixtures of n-butane:n-pentane and isobutane:isopentane, respectively, and on a distillation cut boiling below 145 degrees F of a reference unleaded gasoline blend to assess the nephrotoxicity of these volatile mixtures. The mixtures of butanes and pentanes were selected because these four hydrocarbons are the most prevalent components of gasoline vapors encountered under typical occupational exposures. The 0-145 degrees F gasoline distillation fraction was tested because it reasonably approximates the composition of gasoline vapors measured under occupational settings. Male and female F-344 rats were exposed to 2 levels of each mixture, 6 hours per day, 5 days per week, for 13 weeks. The target concentrations for the butane:pentane mixtures were 4500 and 1000 parts per million (ppm), while 5200 and 1200 ppm were set for the gasoline distillation fraction. An interim sacrifice was conducted after 28 days. The rats were not significantly affected by the exposures, and there was no evidence of hydrocarbon-induced nephropathy in either sex at the termination of each study. However, at the 28-day interim sacrifice period for both butane:pentane mixtures, mild, transient treatment-related but not exposure-related kidney effects were observed in the male rats. These perturbations were absent at the interim sacrifice period for the gasoline distillation fraction.     

Quantitative analysis of urinary ethylene glycol in rats exposed to ethylene oxide

A gas chromatographic method was used for determining ethylene glycol in urine. The analytical procedure is based on an azeotropic distillation and on esterification with n-butyl boronic acid. The linear calibration curve was obtained up to 500 micrograms/ml of ethylene glycol. The detection limit was estimated to be 10 micrograms/ml and relative standard deviation was 3.5% for 100 micrograms/ml of ethylene glycol. This method was applied to determine the urinary excretion of ethylene glycol in rats exposed to ethylene oxide at various concentrations (from 50 to 500 ppm). The excretion amounts of ethylene glycol were observed to be dependent on the concentration of ethylene oxide exposed.     

Glutathione peroxidase system and lysozyme in rats exposed to ozone or nitrogen dioxide

Exposure of rats to low concentrations of ozone (as low as 0.2 ppm) continuously for 8 days, or intermittently (8 hours/day) for 7 days, significantly increased the activities of the glutathione (GSH) peroxidase system in lung tissue. Linear regression analysis showed the increased enzymic activities to be a function of ozone concentration. Lysozyme activity was significantly increased in lung soluble and plasma, during continuous but not intermittent ozone exposure. The results indicated that lipid peroxidation damage occurred in lungs of rats exposed to relatively high levels of ozone. Rats were exposed to relatively higher levels of nitrogen dioxide for 4 days. The activities of GSH reductase and glucose-6-phosphate dehydrogenase were significantly increased during exposure to 2.3 ppm and 6.2 ppm nitrogen dioxide, respectively. There was no significant increase in the activity of GSH peroxidase in lung soluble, or of lysozyme in the plasma, during exposure to nitrogen dioxide. The results suggest that the mechanism of action of nitrogen dioxide is different from that of ozone.     

染矽尘大鼠血浆一氧化氮、一氧化氮合酶的变化

目的　探讨染矽尘不同时点大鼠血浆NO (一氧化氮 )、NOS (一氧化氮合酶 )的变化。方法　采用析因分析的研究设计进行实验 ;气管注射染尘方法建立动物模型 ;称量法测定脏器系数 ;硝酸还原酶法测定血浆NO水平 ;NOS催化L Arg法测定血浆NOS活性。结果　在染尘后第 30天时 ,实验组血浆NO水平高于对照组 (P <0 0 5) ,其他时点差异没有显著性 ,但有升高趋势 ;在染尘后第 2 1、 30、 60天时 ,实验组血浆NOS活力显著低于对照组。控制时间因素进行偏相关分析结果显示实验组血浆NO水平和血浆NOS活力为负相关 (r=- 0 367,P =0 0 2 8)。结论　矽尘可导致大鼠血浆NO水平升高和血浆NOS活力的降低     

Changes of cardiac and respiratory rhythm in non- and tracheostomized rats exposed to nitrogen dioxide

Cardiac and respiratory changes in non- and tracheostomized rats were examined during exposure to 20 ppm of NO₂ for 150 min. The abnormal respiratory pattern consisted of rapid shallow breathing, deep breathing, and apnea, and the bradyarrhythmias were observed in the tracheostomized rats during exposure. Also, similar changes were seen in the nontracheostomized rats. A decrease in the heart rate (HR) was observed in both non- and tracheostomized rats. The decrease in HR was depressed by atropine injection, and the abnormal respiratory patterns were almost abolished by this drug. It was suggested, from these results, that the cardiac and respiratory abnormalities could be induced without the irritation to upper respiratory tracts, and that the vagal efferent pathway had an important role in the appearance of the abnormalities during exposure.     

Decreased phagocytosis and superoxide anion production in alveolar macrophages of rats exposed to nitrogen dioxide

Effects of nitrogen dioxide (NO₂) on pulmonary defense systems were investigated by determining phagocytosis and Superoxide anion (O ₂ ^– ) production by alveolar macrophages (AM) of rats. Rats were exposed to 8 ppm NO₂ for 1 to 7 days and 4 ppm NO₂ for 1 to 10 days, respectively. The phagocytic activity of AM was determined by taking yeast particles into the cells. The O ₂ ^– production by AM was determined at rest during phagocytosis of zymosan particles and stimulation with phorbol myristate acetate (PMA). The suppression of phagocytosis of AM was observed in cells from rats exposed to 8 ppm NO₂ for 5 and 7 days. The suppression was also shown in AM from rats exposed to 4 ppm NO₂ for 7 days. There were remarkable decreases in the O ₂ ^– production by AM from 8 ppm NO₂-exposed rats at rest during zymosan phagocytosis and PMA stimulation on and after day 3. The O ₂ ^– production by AM from 4 ppm NO₂-exposed rats at rest and during zymosan phagocytosis decreased on days 3, 5, and 10, but remained unchanged on day 7. The O ₂ ^– production by PMA-stimulated AM from 4 ppm NO₂-exposed rats decreased on day 3. The results suggest that such diminution in phagocytosis and O ₂ ^– production by AM from NO₂-exposed rats demonstrated the adverse effects on the pulmonary early defense systems and potentially causes bacterial infections.     

牛磺酸对染矽尘大鼠肺组织一氧化氮合酶表达的影响

目的探讨饮食中添加牛磺酸对染矽尘大鼠肺组织诱导型一氧化氮合酶(iNOS)表达的作用。方法采用气管暴露法建立矽肺动物模型，部分动物在饲料中添加牛磺酸(牛磺酸组)；高效液相色谱法测定动物血浆中牛磺酸含量。链霉抗生物素蛋白一过氧化物酶法(SP法)结合组织芯片技术检测矽肺动物模型的肺组织iNOS的表达，用Image-Pro Plus图像分析系统对iNOS定量分析。结果牛磺酸组大鼠各时间点血浆中牛磺酸含量高于对照组和染矽尘组，差异均有统计学意义(P＜0．05)。染矽尘组大鼠支气管肺泡灌洗液(BALF)中总NOS活力、iNOS活力和肺组织iNOS阳性面积百分比都在染尘后第14天左右达高峰，分别比对照组增加1．84u／ml、1．12u／ml和5．42％，差异均有统计学意义(P＜0．05)。牛磺酸组与染矽尘组相比，BALF总NOS活力、iNOS活力和肺组织iNOS阳性面积百分比差异均无统计学意义(P＞0．05)。结论牛磺酸对矽尘所诱导的大鼠肺组织iNOS蛋白表达的增加未见明显影响。     

Cadmium content of lung,liver and kidney in rats exposed to cadmium oxide fumes

Summary Young male rats were submitted to five consecutive exposures to atmospheres containing cadmium oxide particles (280 min × mg/m³) and sacrificed at different times of a three months post-exposure period. Time-course evolution of lung, liver and kidney weight as well as cadmium content of these organs were studied by polynomial regression analysis.Growth of lungs was profoundly disturbed in rats exposed to the aerosol and some degree of permanent damage of pulmonary lobes could be evidenced by macroscopic examination. Liver growth was affected to a less extent and no effect on the growth of kidneys was observed.Results showed that 12% of inhaled cadmium are deposited in lungs. Clearance of pulmonary cadmium was slow, exponential and monophasic (half-life 56 days). A slight, but statistically significant, accumulation of the toxic element in liver and kidney was seen.The results suggest that 60% of the lung-deposited cadmium are absorbed.