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Sample records for rats inhaling carbon

  1. Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina.

    Directory of Open Access Journals (Sweden)

    Nils Schallner

    Full Text Available Ischemia and reperfusion injury (I/R of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO after I/R injury ('postconditioning' would protect retinal ganglion cells (RGC.Retinal I/R injury was performed in Sprague-Dawley rats (n = 8 by increasing ocular pressure (120 mmHg, 1 h. Rats inhaled room air or CO (250 ppm for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg. Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining.Inhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9 ± 0.3 vs. 1.4 ± 0.2, p = 0.028; caspase-3: 2.0 ± 0.2 vs. 1.5 ± 0.1, p = 0.007; mean ± S.D., fold induction at 12 h, while expression of Bcl-2 was induced (1.2 ± 0.2 vs. 1.6 ± 0.2, p = 0.001; mean ± S.D., fold induction at 12 h. CO postconditioning suppressed retinal p38 phosphorylation (p = 0.023 at 24 h and induced the phosphorylation of ERK-1/2 (p<0.001 at 24 h. CO postconditioning inhibited the expression of HO-1. The activation of NF-κB, microglia and Müller cells was potently inhibited by CO as well as immigration of proliferative microglia and macrophages into the retina. CO protected I/R-injured RGC with a therapeutic window at least up to 3 h (n = 8; RGC/mm(2; mean ± S.D.: 1255 ± 327 I/R only vs. 1956 ± 157 immediate CO treatment, vs. 1830 ± 109 1.5 h time lag and vs. 1626 ± 122 3 h time lag; p<0.001. Inhibition of ERK-1/2 did not counteract the CO effects (RGC/mm(2: 1956 ± 157 vs. 1931 ± 124, mean ± S.D., p

  2. Pulmonary retention and tissue distribution of 239Pu nitrate in F344 rats and syrian hamsters inhaling carbon tetrachloride

    International Nuclear Information System (INIS)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L.; Nikula, K.J.

    1994-01-01

    Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is possible that nuclear plant workers have been exposed to CCl 4 and plutonium compounds. Potential for future exposure exists during open-quotes cleanupclose quotes operations at weapon production sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. The current Threshold Limit Value for CCl 4 is 5 ppm; however, concentrations of CCl 4 occurring in the nuclear weapons facilities over the past 40-50 y are unknown and may have exceeded this value. The pilot study described in this report is designed to determine whether subchronic inhalation of CCl 4 by CDF register (F-344)/CrlBR rats and Syrian golden hamsters, at concentrations expected to produce some histologic changes in liver, alters the hepatic retention and toxic effects of inhaled 239 Pu nitrate 239 Pu(NO 3 ) 4

  3. Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by Inhalation Exposure in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2011-09-01

    Conclusion: We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 × 106 particles/cm3 in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.

  4. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    International Nuclear Information System (INIS)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L.

    1995-01-01

    Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl 4 and plutonium compounds. Future exposures may occur during open-quotes cleanupclose quotes operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl 4 by hamsters reduces uptake of 239 Pu solubilized from lung, shunting the 239 Pu to the skeleton

  5. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L. [and others

    1995-12-01

    Carbon tetrachloride (CCl{sub 4}) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl{sub 4} and plutonium compounds. Future exposures may occur during {open_quotes}cleanup{close_quotes} operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl{sub 4} by hamsters reduces uptake of {sup 239}Pu solubilized from lung, shunting the {sup 239}Pu to the skeleton.

  6. Dichloromethane and carbon monoxide inhalation: carboxyhemoglobin addition, and drug metabolizing enzymes in rat

    Energy Technology Data Exchange (ETDEWEB)

    Kurppa, K.; Kivistoe, H.; Vainio, H.

    1981-09-01

    Male Wistar rats were exposed for 3 h to 100 ppm CO, 1,000 ppm dichloromethane, or to their combination. Exposure to dichloromethane alone or in combination with CO doubled the ethoxycoumarin O-deethylase activity in the kidney microsomes but not in the liver. An additive effect on blood COHb concentration by simultaneous exposure to CO and dichloromethane was observed. The mechanism of the additive effect is discussed.

  7. Comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11.5 hr/day

    International Nuclear Information System (INIS)

    Paustenbach, D.J.; Carlson, G.P.; Christian, J.E.; Born, G.S.

    1986-01-01

    To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride ( 14 CCl 4 ) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of 14 C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, 14 CCl 4 in the breath and 14 C activity in the feces comprised 45 and 48% of the total 14 C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl 4 . Regardless of the period of exposure, less than 8% of the inhaled 14 CCl 4 was excreted in the urine and less than 2% was exhaled in the breath as the 14 CO 2 metabolite. Approximately 97-98% of the 14 C activity in the expired air was 14 CCl 4 . The quantities of 14 C noted in the feces and urine suggest that more than 60% of the inhaled CCl 4 was metabolized. Elimination of 14 CCl 4 and 14 CO 2 in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of 14 CCl 4 in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of 14 CO 2 in the breath

  8. Fate of inhaled azodicarbonamide in rats

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

    1987-01-01

    Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [ 14 C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14 C-labeled compound present in excreta. [ 14 C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [ 14 C]ADA equivalents were not observed. The rate of buildup of [ 14 C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [ 14 C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine

  9. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures.

    Science.gov (United States)

    Pauluhn, Jürgen

    2010-01-01

    Wistar rats were nose-only exposed to multiwalled carbon nanotubes (MWCNT, Baytubes) in a subchronic 13-week inhalation study. The focus of study was on respiratory tract and systemic toxicity, including analysis of MWCNT biokinetics in the lungs and lung-associated lymph nodes (LALNs). The time course and concentration dependence of pulmonary effects were examined by bronchoalveolar lavage (BAL) and histopathology up to 6 months postexposure. Particular emphasis was directed to the comparative characterization of MWCNT structures prior to and after micronization and dry powder dispersion into inhalation chambers. These determinations were complemented by additional analyses in digested BAL cells. Animals were exposed on 6 h/day, 5 days per week for 13 consecutive weeks to 0, 0.1, 0.4, 1.5, and 6 mg/m(3). The subchronic exposure to respirable solid aerosols of MWCNT was tolerated without effects suggestive of systemic toxicity. Kinetic analyses demonstrated a markedly delayed clearance of MWCNT from lungs at overload conditions. Translocation into LALNs occurred at 1.5 and 6 mg/m(3) and required at least 13 weeks of study to become detectable. At these exposure levels, the lung and LALN weights were significantly increased. Sustained elevations in BAL polymorphonuclear neutrophils and soluble collagen occurred at these concentrations with borderline effects at 0.4 mg/m(3). Histopathology revealed principal exposure-related lesions at 0.4 mg/m(3) and above in the upper respiratory tract (goblet cell hyper- and/or metaplasia, eosinophilic globules, and focal turbinate remodeling) and the lower respiratory tract (inflammatory changes in the bronchioloalveolar region and increased interstitial collagen staining). Granulomatous changes and a time-dependent increase of a bronchioloalveolar hyperplasia occurred at 6 mg/m(3). All end points examined were unremarkable at 0.1 mg/m(3) (no-observed-adverse-effect-level). In summary, this study demonstrates that the induced

  10. Inhalative cadmium effects in pregnant and fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Prigge, E.

    1978-01-01

    Pregnant and non-pregnant rats were continuously exposed for 21 days to an aerosol containing 0.2, 0.4, and 0.6 mg cadmium/m/sup 3/ air. Pregnant and non-pregnant rats exposed to clean air served as controls. The aerosol was generated by an ultrasonic nebulizer and was carried into inhalation chambers. The median aerodynamic diameters were on the order of 0.6 ..mu..m. After inhalation of cadmium aerosols, serum iron levels were not lowered significantly in adult rats. A polycythaemic response of non-pregnant rats was observed due to a direct stimulatory effect of cadmium on erythropoiesis. Polycythaemia was less marked in pregnancy, presumably due to iron loss to placenta and fetus. Disturbances of pulmonary gas exchange or decreased plasma volumes were excluded as causative mechanisms of polycythaemia. In pregnant rats there was a marked dose dependent decrease of the activity of the alkaline phosphatase after cadmium inhalation, while there was no effect in exposed non-pregnant rats. This decreased enzyme activity, together with slowed growth rates and hemolytic effect indicate a higher sensitivity to cadmium in pregnancy. Proteinuria was not found in neither pregnant nor non-pregnant rats. Therefore, it is concluded that in this respect cadmium intoxication by inhalation does not resemble human toxemia of pregnancy, as discussed in the literature.

  11. The reproductive dysfunction effects of gasoline inhalation in albino rats.

    Science.gov (United States)

    Ugwoke, C C; Nwobodo, E D; Unekwe, P; Odike, M; Chukwumai, S T; Amilo, G

    2005-01-01

    Daily exposure to fuel vapour may pose significant health risk to exposed individuals. Fifteen each of male and female albino rats weighing between 110-230g were divided into test (10) and control (5) groups each. The test animals; were exposed to inhalation gasoline for one hour daily for twenty-one consecutive days. All animals were then bled and the serum levels of the reproductive hormones determined. The results showed significant [P inhalation gasoline exposure significantly [P < 0.05] lowers the levels of reproductive hormones in albino rats and may thus interfere with reproduction.

  12. A rat model of smoke inhalation injury: Influence of combustion smoke on gene expression in the brain

    International Nuclear Information System (INIS)

    Lee, Heung M.; Greeley, George H.; Herndon, David N.; Sinha, Mala; Luxon, Bruce A.; Englander, Ella W.

    2005-01-01

    Acute smoke inhalation causes death and injury in victims of home and industrial fires as well as victims of combat situations. The lethal factors in combustion smoke inhalation are toxic gases and oxygen deficiency, with carbon monoxide (CO) as a primary cause of death. In survivors, inhalation of smoke can result in severe immediate and delayed neuropathologies. To gain insight into the progression of molecular events contributing to smoke inhalation sequelae in the brain, we developed a smoke inhalation rat model and conducted a genome-wide analysis of gene expression. Microarray analysis revealed a modified brain transcriptome with changes peaking at 24 h and subsiding within 7 days post-smoke. Overall, smoke inhalation downregulated genes associated with synaptic function, neurotransmission, and neurotrophic support, and upregulated genes associated with stress responses, including nitric oxide synthesis, antioxidant defenses, proteolysis, inflammatory response, and glial activation. Notably, among the affected genes, many have been previously implicated in other types of brain injury, demonstrating the usefulness of microarrays for analysis of changes in gene expression in complex insults. In accord with previously described modulations of nitric oxide homeostasis in CO poisoning, microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke. Furthermore, immunostaining showed significant elevations in perivascular NOS and in protein nitration, corroborating the involvement of nitric oxide perturbations in post-smoke sequelae in the brain. Thus, the new rat model, in combination with microarray analyses, affords insight into the complex molecular pathophysiology of smoke inhalation in the brain

  13. Carbon dioxide inhalation treatments of neurotic anxiety. An overview.

    Science.gov (United States)

    Wolpe, J

    1987-03-01

    A lucky chance more than 30 years ago revealed the remarkable efficacy of single inhalations of high concentrations of carbon dioxide in eliminating or markedly reducing free-floating anxiety. The reduction of anxiety lasts for days, weeks, or longer--well beyond the persistence of carbon dioxide in the body. The effects are explicable on the hypothesis that free-floating anxiety is anxiety conditioned to continuously present sources of stimulation, such as background noise or the awareness of space or time, and that the anxiety response habit is weakened when the anxiety is inhibited by the competition of responses that carbon dioxide induces. More recently, it has become apparent that inhalations of carbon dioxide, applied in a different manner, are effective in overcoming maladaptive anxiety responses to specific stimuli, e.g., social stimuli. The substance is also proving to be a valuable resource in the treatment of the common variety of panic attacks.

  14. Oxidative stress in a rat model of cotton smoke inhalation-induced ...

    African Journals Online (AJOL)

    Background: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. Materials and Methods: ...

  15. Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black.

    Science.gov (United States)

    Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Küttler, Karin; Wohlleben, Wendel; Hofmann, Thomas; Gröters, Sibylle; Wiench, Karin; van Ravenzwaay, Bennard; Landsiedel, Robert

    2013-06-17

    Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in order to avoid unsafe applications or select

  16. Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black

    Science.gov (United States)

    2013-01-01

    Background Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. Methods In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. Results No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. Conclusions The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in

  17. Lung clearance of inhaled particles after exposure to carbon black generated from a resuspension system

    International Nuclear Information System (INIS)

    Lee, P.S.; Gorski, R.A.; Hering, W.E.; Chan, T.L.

    1987-01-01

    A system to resuspend carbon black particles for providing submicron aerosols for inhalation exposure studies has been developed. The effect of continuous exposure to carbonaceous material (as a surrogate for the carbonaceous particles in diesel exhaust) on the pulmonary clearance of inhaled diesel tracer particles was studied in male Fischer 344 rats. Submicron carbon black particles with a mass median aerodynamic diameter (MMAD) of 0.22 micron and a size distribution similar to that of exhaust particles from a GM 5.7-liter diesel engine were successfully generated and administered to test animals at a nominal concentration of 6 mg/m3 for 20 hr/day, 7 days/week, for periods lasting 1 to 11 weeks. Immediately after the carbon black exposure, test animals were administered 14 C-tagged diesel particles for 45 min in a nose-only chamber. The pulmonary retention of inhaled radioactive tracer particles was determined at preselected time intervals. Based upon the data collected up to 1 year postexposure, prolonged exposure to carbon black particles exhibits a similar inhibitory effect on pulmonary clearance as does prolonged exposure to diesel exhaust with a comparable particulate dose. This observation indicates that the excessive accumulation of carbonaceous material may be the predominant factor affecting lung clearance

  18. Lung cancer and inhaled uranium ore dust in rats

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Jackson, J.S.

    1997-01-01

    Using a nose only inhalation system, 187 nine week old male Sprague-Dawley rats were exposed to two different concentrations of natural uranium ore dust aerosol (44% U) without significant radon content. Inhalation exposures averaged about 4.2 h/day, 5 days/week for 65 weeks at which point lung uranium burdens in the two groups averaged 0.9 and 1.9 mg/g dry weight. Animals (63) exposed to the air stream without dust served as controls. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime, a maximum of about 900 days after the start of dust inhalation. Lung uranium burdens were measured at the time of death of each animal. Lung burdens were found to decline exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. All lungs were examined at necropsy and histologically for lung tumors. Lung tumors of lung origin were observed in both exposed groups and in the control group. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control low and high aerosol exposed groups respectively. Absorbed dose to the lung was calculated for each animal in the study. The average maximum doses for all the animals exposed to the low or high concentration of dust aerosol were 0.87 Gy and 1.64 Gy respectively. The average risk of malignant lung tumors from inhaled natural uranium ore dust was therefore about 0.20 tumors/animal/Gy. For animals with lung tumors, the average doses were 0.98 and 1.90 in the exposed groups. In both exposed groups, the frequency of primary malignant or non-malignant lung tumors was significantly greater than in the control group (p < 0.02) and the frequency of primary malignant lung tumors in the two exposed group were significantly different from each other (p = 0.05). The frequency of primary lung tumors (malignant and non-malignant) was calculated as a function of dose

  19. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

    1990-12-01

    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  20. [Etiology of combined inhalational hydrocyanic acid and carbon monoxide poisoning].

    Science.gov (United States)

    Sigrist, T; Dirnhofer, R

    1979-01-01

    A young man was found dead in a kitchen, that was partly burnt. Autopsy revealed, as cause of death, a combined intoxication following inhalation of carbon monoxide and hydrocyanic acid. Own investigations on the pyrolysis of pieces of furniture found in the kitchen (plastic plates containing melamine and plates containing formaldehyde) showed, that hydrocyanic acid was liberated through combustion of such substances and inhaled by the victim. The poisoning picture is discussed, and discussion includes especially considerations on the peculiar sensitivity of the brain toward the action of hydrocyanic acid and the relative insensitivity of the heart muscle. It is thought that the cause of such sensitivity difference lies in the physiological differences of the intracellular energy production. Finally the dangers of combustion gases developing from burning plastic materials are reemphasized.

  1. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    Science.gov (United States)

    Bellmann, B.; Creutzenberg, O.; Ernst, H.; Muhle, H.

    2009-02-01

    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m3. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  2. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    International Nuclear Information System (INIS)

    Bellmann, B; Creutzenberg, O; Ernst, H; Muhle, H

    2009-01-01

    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m 3 . The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  3. Inhalants

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  4. Ferrocene: Disposition following nose-only inhalation by the rat

    International Nuclear Information System (INIS)

    Slauter, R.W.; Tippin, T.K.; Jeffcoat, A.R.; Matthews, H.B.

    1990-01-01

    Ferrocene (FCN) is a volatile solid organometallic proposed for use as an anti-knock additive in gasoline. Such use would provide significant potential for human exposure via inhalation. Nose-only exposure of male F344 rats over 6 h to constant concentrations of 5 and 25 ng of [ 14 C]FCN/mL air was conducted by blending correct proportions of an air stream concentrated with [ 14 C]FCN vapor with one that was FCN free. Fractional pulmonary absorption of FCN was estimated to be ca. 66 and 55% with concentrations of 14 C in blood increasing steadily throughout the exposure period to 80 and 370 ng-eq of FCN/mL, respectively. Disappearance of 14 C from the blood was multiphasic (terminal t 1/2 =∼2 d) following inhalation exposure, resulting in blood concentrations of 10 and 50 ng-eq of FCN/mL 72 h after end of exposure. More than 80% of the recovered 14 C was in the 0-72 h urine, approximately half of which was a single metabolite (radio-HPLC). Unchanged FCN was excreted in only minor amounts ( 14 C were also excreted in feces (ca. 10% of total) and breath (ca. 4% of total). Neither lung nor nasopharynx had tissue to blood ratios of 14 C>3 72 h after exposure. Similar disposition was shown after an iv bolus of 1.0 mg of [ 14 C]FCN/kg body weight

  5. Distribution and retention of inhaled selenium compounds in the rat

    International Nuclear Information System (INIS)

    Burkstaller, M.A.; Cuddihy, R.G.

    1978-01-01

    Selenium containing compounds released into the atmosphere during coal combustion are principally of the elemental form or the dioxide. These compounds differ greatly in their chemical properties. Fischer-344 rats were exposed via inhalation to both the dioxide and the red elemental form of selenium. Subsequently, measurements were made of internal absorption, organ distribution and retention, and modes of excretion. A radiotracer, 75 Se, was incorporated into the aerosol to facilitate these measurements. Retention of both aerosols in the total body showed long term components with half lives of 43 and 15 days accounting for 25 to 35% of the initially deposited selenium. Excretion occurred principally by way of urine. For both aerosols, selenium absorbed into the systemic circulation was mainly found in the liver, kidney, blood, gastrointestinal tract and bone

  6. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    International Nuclear Information System (INIS)

    Oller, Adriana R.; Kirkpatrick, Daniel T.; Radovsky, Ann; Bates, Hudson K.

    2008-01-01

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m 3 nickel metal powder (MMAD = 1.8 μm, GSD = 2.4 μm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m 3 nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m 3 was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m 3 male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m 3 females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies

  7. Inhaled 239PuO2 in rats with pulmonary emphysema

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Mauderly, J.L.; Hahn, F.F.

    1984-01-01

    The modifying effects of a pre-existing lung disease (emphysema) on the deposition, distribution, retention, and effects of inhaled 239 PuO 2 in the rat are being investigated. Preliminary observations indicated that the deposition and retention patterns for 239 Pu particles inhaled by rats with emphysema and control rats were similar, but the distribution of inhaled 239 Pu immediately after exposure was different. Respiratory function measured through one year after exposure to 239 Pu was consistent with emphysema and was not altered by the 239 Pu lung burden. Long-term observations are continuing. 4 references, 2 tables

  8. Inhalants

    Science.gov (United States)

    ... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

  9. Establishment and evaluation of a rat model of inhalation lung injury induced by ship smog

    Directory of Open Access Journals (Sweden)

    Xin-xin DUAN

    2018-03-01

    Full Text Available Objective To establish and evaluate a rat model of inhalation lung injury induced by ship smog. Methods A rat model of inhalation lung injury was established by analyzing the composition of ship materials after combustion. Forty- two healthy male Wistar rats were randomly divided into normal control group and 2, 6, 12, 24, 48 and 72h groups (6 eachafter inhalation, these rats were killed at each time point, and the changes of arterial blood gas, coagulation function, the lung water content (% were detected. Macroscopic and microscopic changes in lung tissues were observed to judge the degree of lung injury. Results The main components after combustion of 7 kinds of nonmetal materials on ship included CO, CO2, H2S, NOx and other harmful gases in this study, AIKE in one gas detector was used to monitor O2, CO, CO2 and H2S, and their concentrations remained relatively stable within 15 minutes, and the injury time was 15 minutes. The rats presented with shortness of breath and mouth breathing. Smoke inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 2h and the lung water content (% did 6h after inhalation (P<0.05. It is metabolic acidosis in the early stage after inhalation, but metabolic acidosis combined with respiratory acidosis in the later period. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in the lung tissue as manifestations of lung injury, and the injury did not recover at 72h after inhalation, the change of blood coagulation function was not statistically significant. Conclusion A rat model of inhalation lung injury induced by ship smog has been successfully established, and has the advantages of easy replication, stability and reliability, thus can be used to research and treat inhalation lung injury induced by ship smog in naval war environment and other cases. DOI: 10.11855/j.issn.0577-7402.2018.03.14

  10. The effects of passive inhalation of cigarette smoke on serum lipid profile in the rat

    Directory of Open Access Journals (Sweden)

    j Rahmani Kahnamoei

    2016-11-01

    Full Text Available Passive cigarette smoke contains five times more carbon monoxide and six times more nicotine compared to the main smoke because cigarette filter has a protective role for smokers. Cigarette smoke contains a range of oxidants and free radicals that can directly or indirectly induce oxidative stress in the body. Adding some aromatic ingredients to cigarette may play an important role in increasing damage and free radicals. The aim of this study was to evaluate the effects of passive inhalation of cigarette smoke on serum lipid profile in rats. For this purpose, 16 male Wistar rats were divided randomly into two groups of eight rats, control and treatment. There was no intervention in the control group, but treatment group was exposed to a cigarette passive smoke on a daily basis for a month. After a month, the rat tail vein blood samples were taken and after separation of the sera, serum lipid profiles, including triglycerides, total cholesterol, LDL and HDL was measured and the results were statistically analyzed using t-test. There was a significant (p

  11. Acute Inhalation Toxicity of T-2 Mycotoxin in the Rat and Guinea Pig

    Science.gov (United States)

    1990-01-01

    2/kg body weight for the guinea pig . These data show that inhaled T-2 toxin is approximately 20 times more toxic to the rat (0.05 mg T-2/kg body wt...inhaled vs 1.0 mg T-2/kg body wt ip) and at least twice as toxic to the guinea pig (0.4 mg T-2/kg body wt inhaled vs 1-2 mg T-2/kg body wt ip) than ip...administered T-2 toxin. Histopathologic examination of major organs in both the rat and guinea pig after respiratory exposure to T-2 toxin indicated

  12. Inhaled 239PuO2 in rats with pulmonary emphysema. II

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Mauderly, J.L.; Carlton, W.W.; Hahn, F.F.

    1988-01-01

    The modifying effects of pre-existing pulmonary emphysema on deposition, distribution, retention, and effects of inhaled 239 PuO 2 in the rat were investigated. The presence of emphysema in the rats tested was indicated by respiratory function measurements and confirmed microscopically. Initial lung burdens of 239 Pu per kg body weight were less in rats with emphysema than in control rats; however, the retention of 239 Pu was similar in emphysematous and control rats. Survival and lung tumor occurrence were similar in emphysematous and control rats exposed to 239 PuO 2 . We concluded that rats with pre-existing pulmonary emphysema were not more sensitive to the effects of inhaled 239 PuO 2 than control rats. (author)

  13. Inhaled {sup 239}PuO{sub 2} in rats with pulmonary emphysema. II

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D L; Mauderly, J L; Carlton, W W; Hahn, F F

    1988-12-01

    The modifying effects of pre-existing pulmonary emphysema on deposition, distribution, retention, and effects of inhaled {sup 239}PuO{sub 2} in the rat were investigated. The presence of emphysema in the rats tested was indicated by respiratory function measurements and confirmed microscopically. Initial lung burdens of {sup 239}Pu per kg body weight were less in rats with emphysema than in control rats; however, the retention of {sup 239}Pu was similar in emphysematous and control rats. Survival and lung tumor occurrence were similar in emphysematous and control rats exposed to {sup 239}PuO{sub 2}. We concluded that rats with pre-existing pulmonary emphysema were not more sensitive to the effects of inhaled {sup 239}PuO{sub 2} than control rats. (author)

  14. Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

    Directory of Open Access Journals (Sweden)

    Yi-fan LIU

    2013-09-01

    Full Text Available Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

  15. Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

    Science.gov (United States)

    Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

    2016-10-01

    Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Graphistrength© C100 MultiWalled Carbon Nanotubes (MWCNT): thirteen-week inhalation toxicity study in rats with 13- and 52-week recovery periods combined with comet and micronucleus assays

    International Nuclear Information System (INIS)

    Régnier, Jean-François; Pothmann-Krings, Daniela; Simar, Sophie; Dony, Eva; Net, Jean-Loïc Le; Beausoleil, Julien

    2017-01-01

    Graphistrength© C100 provides superior electrical and mechanical properties for various applications and is one of the industrial MWCNT referenced in the OECD sponsorship program for the safety testing of nanomaterials. Graphistrength© C100 is formed of MWCNT (ca. 12 walls, outer mean diameter ca. 12 nm, length ca. 1 µm) agglomerated in particles with a granulometry centered on 400 µm. A general feature of MWCNT after inhalation or intratracheal exposures is the induction of an inflammatory reaction in the lungs sometimes associated with local genotoxic effects. Most of the in vitro and in vivo genotoxicity data available on Graphistrength© C100 are negative. However, a weak DNA damage activity in the in vitro and in vivo FPG-modified Comet assays and a weak clastogenic effect in the in vitr o micronucleus test were reported. After investigating different parameters for the aerosol generation, male and female Wistar rats were exposed by nose-only inhalation (6h/day, 5d/week) to target concentrations of 0.05, 0.25 and 5.0 mg/m 3 air of a respirable aerosol (MMAD < 3 µm) and sacrificed immediately after 4 and 13 weeks of exposure and 13 and 52 weeks of recovery after the 13-week exposure. Clinical, biological and histological evaluations were performed according to the OECD TG 413. Broncho-alveolar lavage fluid (BALF) was collected and analysed for cytokines and inflammatory parameters. Immediately after 13 weeks of exposure, chromosomal aberrations in the bone marrow cells of males and females were evaluated by the micronucleus test (OECD TG 474) and DNA damage in the lung, kidney and liver cells of males were assessed by both the standard and the human 8-oxoguanine DNA N-glycosylase 1 (hOGG1)-modified comet assay (OECD TG 489). Concentration-related deposition of black particles (MWCNT) was observed in lungs. At all sacrifice periods, an inflammatory lung reaction was observed in rats exposed to 5.0 mg/m 3 associated with changes in the differential white

  17. Graphistrength© C100 MultiWalled Carbon Nanotubes (MWCNT): thirteen-week inhalation toxicity study in rats with 13- and 52-week recovery periods combined with comet and micronucleus assays

    Science.gov (United States)

    Régnier, Jean-François; Pothmann-Krings, Daniela; Simar, Sophie; Dony, Eva; Le Net, Jean-Loïc; Beausoleil, Julien

    2017-06-01

    Graphistrength© C100 provides superior electrical and mechanical properties for various applications and is one of the industrial MWCNT referenced in the OECD sponsorship program for the safety testing of nanomaterials. Graphistrength© C100 is formed of MWCNT (ca. 12 walls, outer mean diameter ca. 12 nm, length ca. 1 µm) agglomerated in particles with a granulometry centered on 400 µm. A general feature of MWCNT after inhalation or intratracheal exposures is the induction of an inflammatory reaction in the lungs sometimes associated with local genotoxic effects. Most of the in vitro and in vivo genotoxicity data available on Graphistrength© C100 are negative. However, a weak DNA damage activity in the in vitro and in vivo FPG-modified Comet assays and a weak clastogenic effect in the in vitro micronucleus test were reported. After investigating different parameters for the aerosol generation, male and female Wistar rats were exposed by nose-only inhalation (6h/day, 5d/week) to target concentrations of 0.05, 0.25 and 5.0 mg/m3 air of a respirable aerosol (MMAD males and females were evaluated by the micronucleus test (OECD TG 474) and DNA damage in the lung, kidney and liver cells of males were assessed by both the standard and the human 8-oxoguanine DNA N-glycosylase 1 (hOGG1)-modified comet assay (OECD TG 489). Concentration-related deposition of black particles (MWCNT) was observed in lungs. At all sacrifice periods, an inflammatory lung reaction was observed in rats exposed to 5.0 mg/m3 associated with changes in the differential white blood cells counts. The lung inflammation was characterized by changes in the cytological, biochemical and cytokine parameters of the BALF, an increase of the lung weight, an interstitial inflammation mainly around the alveolar ducts at the bronchiole-alveolar junction and a cell hypertrophy/hyperplasia in the terminal and respiratory bronchioles. The slight changes in BALF parameters observed at 0.25 mg/m3 recovered after

  18. Effect of radon inhalations on certain oxyda-reductive enzymes in adrenols of white rats

    International Nuclear Information System (INIS)

    Robaczynski, J.; Kaplonska, J.; Lozinska, E.

    1974-01-01

    Histochemical investigations were carried out on adrenals of white rats after radon inhalations from inhalers in Swieradow-spa. Increased reactions of oxydo-reductive enzymes: NAD tetrazolium reductase, succinic dehydrogenase and glucose-6-phosphate dehydrogenase were observed in the adrenal cortex, particularly in the zona reticularis which was hypertrophied. Raised activity of oxydo-reductive enzymes in the cells of adrenal cortex evidences increased metabolism in these cells which may reflect increased production of hormones. Finding of stimulation of adrenocortical cells after radon inhalations is of essential importance for explanation of the biological mechanism of action of radon used in balneotherapy. (author)

  19. Comparative toxicity in rats vs hamsters of inhaled radon daughters with and without uranium ore dust

    International Nuclear Information System (INIS)

    Gaven, J.C.; Palmer, R.F.; McDonald, K.E.; Lund, J.E.; Stuart, B.O.

    1977-01-01

    Simultaneous exposures of rats and hamsters to inhaled radon daughters, with and without uranium ore dust, were performed daily for five months. Pulmonary pathology developing in 6 to 13 mo after cessation of daily exposures included interstitial fibrosis, emphysema, epithelial hyperplasia, squamous metaplasia, and malignant neoplasia. Rats showed a greater variety and more severe response to these uranium mine inhalation exposures than did hamsters. Inhalation of radon daughters with uranium ore dust displayed the site of greatest damage, including squamous carcinoma, from the nasopharynx to the lungs. Sixty percent of the rats exposed to radon daughters with ore dust developed primary pulmonary carcinomas, providing an appropriate short-term experimental animal model for investigation of respiratory tract carcinogenesis in uranium miners

  20. Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats.

    Science.gov (United States)

    Matsuoka, Tadashi; Suzuki, Masaru; Sano, Motoaki; Hayashida, Kei; Tamura, Tomoyoshi; Homma, Koichiro; Fukuda, Keiichi; Sasaki, Junichi

    2017-09-01

    Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30-35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.

  1. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  2. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  3. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    International Nuclear Information System (INIS)

    Finch, G.L.; Nikula, K.J.; Barr, E.B.

    1995-01-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET γ-irradiation or α-irradiation from inhaled 239 PuO 2 particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled 239 PuO 2 or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + 239 PuO 2 study continue, and the study of CS + X rays is beginning

  4. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  5. Dearomatized white spirit inhalation exposure causes long-lasting neurophysiological changes in rats

    DEFF Research Database (Denmark)

    Lund, S. P.; Simonsen, L.; Hass, Ulla

    1996-01-01

    Dearomatized white spirit inhalation exposure causes long-lasting neurophysioloical changes in rats. NEUROTOXICOL TERATOL 18(1), 67-76, 1996. -Exposure for 6 h per day, 5 days per week, during a period of 6 months to the organic solvent dearomatized white spirit (0, 400, and 800 ppm) was studied ...

  6. Inhalation of Roman chamomile essential oil attenuates depressive-like behaviors in Wistar Kyoto rats.

    Science.gov (United States)

    Kong, Yingying; Wang, Ting; Wang, Rong; Ma, Yichuan; Song, Shanshan; Liu, Juan; Hu, Weiwei; Li, Shengtian

    2017-06-01

    The idea of aromatherapy, using essential oils, has been considered as an alternative antidepressant treatment. In the present study, we investigated the effect of Roman chamomile essential oil inhalation for two weeks on depressive-like behaviors in Wistar-Kyoto (WKY) rats. We found that inhalation of either Roman chamomile or one of its main components α-pinene, attenuated depressive-like behavior in WKY rats in the forced swim test. Using isobaric tags for relative and absolute quantitation analysis (iTRAQ), we found that inhalation of α-pinene increased expression of proteins that are involved in oxidative phosphorylation, such as cytochrome c oxidase subunit 6C-2, cytochrome c oxidase subunit 7A2, ATPase inhibitor in the hippocampus, and cytochrome c oxidase subunit 6C-2, ATP synthase subunit e, Acyl carrier protein, and Cytochrome b-c1 complex subunit 6 in the PFC (prefrontal cortex). In addition, using the quantitative real-time polymerase chain reaction technique, we confirmed an increase of parvalbumin mRNA expression in the hippocampus, which was shown to be upregulated by 2.8-fold in iTRAQ analysis, in α-pinene treated WKY rats. These findings collectively suggest the involvement of mitochondrial functions and parvalbumin-related signaling in the antidepressant effect of α-pinene inhalation.

  7. Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats.

    Science.gov (United States)

    Pujalté, Igor; Dieme, Denis; Haddad, Sami; Serventi, Alessandra Maria; Bouchard, Michèle

    2017-01-04

    This study focused on the generation of aerosols of titanium dioxide (TiO 2 ) nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley rats were exposed by inhalation to 15mg/m 3 of anatase TiO 2 NPs (∼20nm) during 6h. Rats were sacrificed at different time points over 14days following the onset of inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta. Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were found in lungs; peak values were reached only at 48h followed by a progressive decrease over 14days, suggesting a persistence of NPs at the site-of-entry. Levels reached in blood, lymph nodes and other internal organs (including liver, kidney, spleen) were circa one order of magnitude lower than in lungs, but the profiles were indicative of a certain translocation to the systemic circulation. Large amounts were recovered in feces compared to urine, suggesting that inhaled NPs were eliminated mainly by mucociliary clearance and ingested. TiO 2 NPs also appeared to be partly transferred to olfactory bulbs and brain. MDA levels indicative of oxidative damage were significantly increased in lungs and blood at 24h but this was not clearly reflected at later times. Translocation and clearance rates of inhaled NPs under different realistic exposure conditions should be further documented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Carbon monoxide inhalation induces headache in a human headache model

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2018-01-01

    , double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0-10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial...

  9. [Teratologic cranio-encephalic effects of chronic thinner inhalation in progenitors, in rats and humans].

    Science.gov (United States)

    Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M

    1991-01-01

    Inhalation of thinner by youngsters and adolescents is an increasing drug abuse problem in Mexico. It presents serious repercussions upon socio-economic, cultural, legal and health (neurologic and psychiatric) problems. We report a comparative study in humans and rats which demonstrate the embryotoxic and craneo encephalic teratologic effects in the children and brood of progenitors who have chronically inhaled thinner (in the case of pregnant women, before, at the beginning and throughout pregnancy). Inhaled thinner passes directly to the blood stream and crosses the placentary barrier freely reaching the embryo. It may cause craneal bone and partial or total encephalon agenesia, added to macro and microscopic lesions secondary to direct aggression to the neuroepithelial germ cells. Abortions and premature labor with weight and size underdeveloped products and placentary hemorrhages occur. Usually these die, but if they survive they show trascendental mental retardation, as well as neurologic and psychiatric sequels.

  10. CHARACTERIZATION OF THE EFFECTS OF INHALED PERCHLOROETHYLENE ON SUSTAINED ATTENTION IN RATS PERFORMING A VISUAL SIGNAL DETECTION TASK

    Science.gov (United States)

    The aliphatic hydrocarbon perchloroethyelene (PCE) has been associated with neurobehavioral dysfunction including reduced attention in humans. The current study sought to assess the effects of inhaled PCE on sustained attention in rats performing a visual signal detection task (S...

  11. Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse.

    Science.gov (United States)

    Martínez-Alfaro, Minerva; Cárabez-Trejo, Alfonso; Gallegos-Corona, Marco-Antonio; Pedraza-Aboytes, Gustavo; Hernández-Chan, Nancy Georgina; Leo-Amador, Guillermo Enrique

    2010-04-01

    Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Numerous studies of workers for genotoxic effects of thinner exposure have yielded conflicting results, perhaps because co-exposure to variable other compounds cannot be avoided in workplace exposure studies. In contrast, there is no data concerning the genotoxic effects of intentional inhalation abuse. The aim of this project was to examine the genotoxic effects of thinner inhalation in an animal model of thinner abuse (rats exposed to 3000 ppm toluene, a high solvent concentration over a very short, 15 min time period, twice a day for 6 weeks). The data presented here provides evidence that thinner inhalation in our experimental conditions is able to induce weight loss, lung abnormalities and oxidative stress. This oxidative stress induces oxidative DNA damage that is not a characteristic feature of genotoxic damage. No significant difference in DNA damage and DNA repair (biomarkers of genotoxicity) in lymphocytes from thinner-treated and control rats was found. Lead treatment was used as a positive control in these assays. Finally, bone marrow was evaluated as a biomarker of cellular alteration associated with thinner inhalation. The observed absence of hemopoietic and genetic toxicity could be explained in part by the absence of benzene, the only carcinogenic component of thinner; however, benzene is no longer a common component of thinner. In conclusion, thinner did not cause genotoxic effects in an experimental model of intentional abuse despite the fact that thinner inhalation induces oxidative stress. (c) 2009 John Wiley & Sons, Ltd.

  12. Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat.

    Science.gov (United States)

    Poon, R; Chu, I; Bjarnason, S; Vincent, R; Potvin, M; Miller, R B; Valli, V E

    1995-01-01

    Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects

  13. Effect of carbon dioxide inhalation on pulmonary hypertension induced by increased blood flow and hypoxia

    Directory of Open Access Journals (Sweden)

    I-Chun Chuang

    2011-08-01

    Full Text Available There is now increasing evidence from the experimental and clinical setting that therapeutic hypercapnia from intentionally inspired carbon dioxide (CO2 or lower tidal volume might be a beneficial adjunct to the strategies of mechanical ventilation in critical illness. Although previous reports indicate that CO2 exerts a beneficial effect in the lungs, the pulmonary vascular response to hypercapnia under various conditions remains to be clarified. The purpose of the present study is to characterize the pulmonary vascular response to CO2 under the different conditions of pulmonary hypertension secondary to increased pulmonary blood flow and secondary to hypoxic pulmonary vasoconstriction. Isolated rat lung (n = 32 was used to study (1 the vasoactive action of 5% CO2 in either N2 (hypoxic-hypercapnia or air (normoxic-hypercapnia at different pulmonary arterial pressure levels induced by graded speed of perfusion flow and (2 the role of nitric oxide (NO in mediating the pulmonary vascular response to hypercapnia, hypoxia, and flow-associated pulmonary hypertension. The results indicated that inhaled CO2 reversed pulmonary hypertension induced by hypoxia but not by flow alteration. Endogenous NO attenuates hypoxic pulmonary vasoconstriction but does not augment the CO2-induced vasodilatation. Acute change in blood flow does not alter the endogenous NO production.

  14. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat

    International Nuclear Information System (INIS)

    Monleau, M.

    2005-12-01

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  15. Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats.

    Science.gov (United States)

    Petitot, Fabrice; Lestaevel, Philippe; Tourlonias, Elie; Mazzucco, Charline; Jacquinot, Sébastien; Dhieux, Bernadette; Delissen, Olivia; Tournier, Benjamin B; Gensdarmes, François; Beaunier, Patricia; Dublineau, Isabelle

    2013-03-13

    Uranium nanoparticles (fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account. In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally. For this purpose, rats were exposed to an aerosol containing 10⁷ particles of uranium per cm³ (CMD=38 nm) for 1h in a nose-only inhalation exposure system. Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP-MS. Twenty-seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract. One-fifth of UO₂ nanoparticles were rapidly cleared from lung (T(½)=2.4 h) and translocated to extrathoracic organs. However, the majority of the particles were cleared slowly (T(½)=141.5 d). Future long-term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Toxicity of inhaled 239PuO2 in Fischer 344 rats

    International Nuclear Information System (INIS)

    Redman, H.C.; Boecker, B.B.; Muggenburg, B.A.; Griffith, W.C.; Guilmette, R.A.; Mewhinney, J.A.; Scott, B.R.

    1979-01-01

    Studies on the biological effects of inhaled particles of 239 PuO 2 have been initiated in the Fischer 344 rat. To obtain information on the importance of homogeneity or nonhomogeneity of radiation dose to the lung, young adult (84 +- 7 days) animals have been exposed to monodisperse aerosols (sigma/sub g/ 239 PuO 2 of 1.0 and 2.8 μm aerodynamic diameter (AD). To determine the effects of age at exposure, aged rats (600 to 660 days) have been exposed to monodisperse aerosols of 239 PuO 2 of 1.0 μm aerodynamic diameter. To date, 480 young adult rats have been exposed to 239 PuO 2 : 240 rats to 1.0 μm AD particles and 240 rats to 2.85 μm AD particles. The projected exposure level ranged from 0.012 to 0.115 μCi/kg body weight. One hundred sixty rats were sham-exposed and maintained as controls. Also, 240 aged rats have been exposed to date to 1.0 μm AD particles of 239 PuO 2 . The projected activity level ranged from 0.012 to 0.115 μCi/kg body weight. Eighty rats were sham-exposed and maintained as controls. In addition, a serial sacrifice study to determine radiation-dose pattern in rats resulting from the inhalation of these monodisperse aerosols of 239 PuO 2 has been initiated in the young adult rat

  17. Combined effects of inhaled plutonium oxide and benzo[a]pyrene on lung carcinogenesis in rats

    International Nuclear Information System (INIS)

    Metivier, H.; Masse, R.; Wahrendorf, J.; Lafuma, J.

    1986-01-01

    This study describes the effect of two intratracheal instillations (5 mg each) of benzo[a]pyrene (BP) on lung carcinogenesis in rats that had previously inhaled three levels of 239 PuO 2 . The BP does not modify survival in the high-level 239 PuO 2 -exposed rats, but markedly reduces survival in the two other groups. Median survival time with BP alone is shorter (666 days) than for the control group (838 days). Tumor incidence was increased by BP exposure, and the tumors were usually fatal, whereas tumors observed after 239 PuO 2 inhalation alone were usually not fatal. Statistical analysis of these data poses a problem because of the need to compare incidental and fatal tumors. 22 refs., 5 figs., 7 tabs

  18. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.

    1994-02-01

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  19. Effect of Inhaling Bergamot Oil on Depression-Related Behaviors in Chronic Stressed Rats.

    Science.gov (United States)

    Saiyudthong, Somrudee; Mekseepralard, Chantana

    2015-10-01

    Bergamot essential oil (BEO) possesses sedation and anxiolytic properties similar to diazepam. After long period of exposure to stressors, including restrained stress, depressive-like behavior can be produced. BEO has been suggested to reduce depression. However, there is no scientific evidence supporting this property. To investigate the effect of BEO in chronic stressed rats on: 1) behavior related depressive disorder, 2) hypothalamic pituitary adrenal (HPA) axis response, and iii) brain-derived neurotrophic factor (BDNF) protein levels in hippocampus. Male Wistar rats, weighing 200 to 250 g, were induced chronic restrained stress 15 minutes dailyfor two weeks. For the next two weeks, these rats were divided intofour groups, control-i.p., fluoxetine-i.p., control-inhale, and BEO-inhale. Fluoxetine (10 mg/kg i.p.) or saline was intraperitoneally administered daily while 2.5% BEO or saline was inhaled daily. At the end of the treatment, rats were assessed for depressive-like behavior using the forced swimming test (FST). After the behavioral test, the animals were immediately decapitated and trunk blood samples were collected for the measurement ofcorticosterone and adrenocorticotropic hormone (ACTH) levels and hippocampus was dissected and stored in afreezer at -80 °C until assay for BDNF protein. BEO andfluoxetine significantly decreased the immobility time in the FST (p BDNF protein determination, neither BEO norfluoxetine had any effect on BDNF protein levels in hippocampus compared to their controls. The inhalation ofBEO decrease behavior related depressive disorder similar tofluoxetine but has no effect on HPA axis response and BDNF protein levels in chronic restrained stress.

  20. Effects of Post-Treatment Hydrogen Gas Inhalation on Uveitis Induced by Endotoxin in Rats.

    Science.gov (United States)

    Yan, Weiming; Chen, Tao; Long, Pan; Zhang, Zhe; Liu, Qian; Wang, Xiaocheng; An, Jing; Zhang, Zuoming

    2018-06-07

    BACKGROUND Molecular hydrogen (H2) has been widely reported to have benefiicial effects in diverse animal models and human disease through reduction of oxidative stress and inflammation. The aim of this study was to investigate whether hydrogen gas could ameliorate endotoxin-induced uveitis (EIU) in rats. MATERIAL AND METHODS Male Sprague-Dawley rats were divided into a normal group, a model group, a nitrogen-oxygen (N-O) group, and a hydrogen-oxygen (H-O) group. EIU was induced in rats of the latter 3 groups by injection of lipopolysaccharide (LPS). After that, rats in the N-O group inhaled a gas mixture of 67% N2 and 33% O2, while those in the H-O group inhaled a gas mixture of 67% H2 and 33% O2. All rats were graded according to the signs of uveitis after electroretinography (ERG) examination. Protein concentration in the aqueous humor (AqH) was measured. Furthermore, hematoxylin-eosin staining and immunostaining of anti-ionized calcium-binding adapter molecule 1 (Iba1) in the iris and ciliary body (ICB) were carried out. RESULTS No statistically significant differences existed in the graded score of uveitis and the b-wave peak time in the Dark-adapted 3.0 ERG among the model, N-O, and H-O groups (P>0.05), while rats of the H-O group showed a lower concentration of AqH protein than that of the model or N-O group (P0.05), while the activation of microglia cells in the H-O group was somewhat reduced (Ptreatment hydrogen gas inhalation did not ameliorate the clinical signs, or reduce the infiltrating cells of EIU. However, it inhibited the elevation of protein in the AqH and reduced the microglia activation.

  1. Developmental neurotoxicity after toluene inhalation exposure in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, Søren Peter; Hougaard, Karin Sørig

    1999-01-01

    Rats were exposed to 1200 ppm or 0 ppm toluene (CAS 108-88-3) for 6 h per day from day 7 of pregnancy until day 18 postnatally. Developmental and neurobehavioral effects in the offspring were investigated using a test battery including assessment of functions similar to those in the proposed OECD...

  2. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2012-09-01

    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  3. The effects of acute gasoline vapour inhalation on some haematological indices of albino Wistar rats

    OpenAIRE

    Chukwudi Onyeka John Okonkwo; Ailende Daniel Ehileboh; Eddy Nwobodo; Charles Chijioke Dike

    2016-01-01

    Objective: To find out if Gasoline vapour has some effects on haematological indices when inhaled by experimental rats. Methods: The standard method for laboratory operating procedure recommended by World Health Organization was used in all the analysis done. Forty two albino Wistar rats comprising twenty one males (160–220 g) and twenty one females (140–190 g) were sampled into six groups consisting of four test groups and two control groups. The test groups were exposed to gasoline vapou...

  4. Toxicity of lunar dust assessed in inhalation-exposed rats.

    Science.gov (United States)

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  5. Comments on the rat lung as a human surrogate in inhalation studies

    International Nuclear Information System (INIS)

    Koblinger, L.

    1988-01-01

    The laboratory rat is often used as a surrogate to estimate the hazard to human health following inhalation exposure to ambient aerosols. Extrapolation of rat deposition data to humans depends, however, on the similarities and differences between the morphometric structures of the two airway systems. The main structural difference between the lungs of the two species, aside from dimensions per se, is their respective airway branching pattern : while the human lung is a rather symmetrically, dichotomously dividing system, the rat network is a more monopodial branching structure. In our stochastic modelling approach to defining suitable morphologies for human and rat lung, we utilise measured morphometric dimensions as the data base upon which a rigorous statistical analysis is performed, instead of forcing them into a formalised, average pathway scheme. This stochastic approach allows us, therefore, to account for structural irregularities, such as asymmetric branching, monopodial structure, and inter and intra-subject variability

  6. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  7. Low-level inhaled-239PuO2 life-span studies in rats

    International Nuclear Information System (INIS)

    Sanders, C.L.; McDonald, K.E.; Killand, B.W.; Mahaffey, J.A.; Cannon, W.C.

    1986-01-01

    This study determined the dose-response curve for lung tumor incidence in rats after inhalation of high-fired 239 PuO 2 , which gave radiation doses to the lung of from ∼5 to >1000 rads. Exposed rats were given a single, nose-only, inhalation exposure to 169 Yb- 239 PuO 2 aerosol (AMAD, 1.6 +- 0.11 μm). The effective half-time for 169 Yb in the lung was 14 days, whereas ∼76% of 239 Pu was cleared with a half-time of 20 days and 24%, with a half-time of 180 days. Whole-body counting for 169 Yb at 14 days after exposure was an accurate method for determining 239 Pu IAD in individual rats, even at IAD's as low as 0.60 nCi of 239 Pu. The 239 Pu lung-clearance curve and an equation describing changes in lung weight with body weight and age were used to determine lung radiation doses. The IAD's of exposure groups were 0.60 +- 0.15 nCi of 239 Pu (1000 rats), 0.98 +- 0.25 (531 rats), 2.4 +- 0.69 (209 rats), 5.7 +- 1.2 (98 rats), and 7.5 +- 2.0 to 150 +- 37 nCi (300 rats); corresponding radiation doses to the lung estimated at 3 years after exposure were 8.3, 14, 33, 79, and 100 to 2100 rads, respectively. 71 refs., 5 figs., 4 tabs

  8. Metabolism of inhaled ethane and pentane by the intact rat

    International Nuclear Information System (INIS)

    Daugherty, M.S.; Luddent, T.M.; Burk, R.F.

    1986-01-01

    Measurement of exhaled ethane or pentane is a noninvasive technique for studying in vivo lipid peroxidation. Many past studies have assumed that pentane and ethane are not metabolized. Radiolabeled ( 14 C) ethane and pentane were used to study the disposition of these compounds in intact rats. Rats were placed for 8 h in a closed plexiglass chamber fitted with a system for replenishing chamber atmospheric O 2 . Evolved CO 2 was trapped by recirculating chamber air through 3 N NaOH contained in a vessel external to the chamber. Radiolabeled ethane or pentane was injected into the chamber at the start of each experiment. The percent of 14 C-activity added to the chamber recovered in the CO 2 trap, urine, and chamber air at the end of the experiment (8 h) in the [ 14 C]-ethane (n=5) and [ 14 C]-pentane (n=4) studies are presented. Results indicate that both ethane and pentane are metabolized to CO 2 in the intact rat. Possible changes in ethane and pentane metabolism must be considered if the exhalation rates of these hydrocarbons are to be used as indices of in vivo lipid peroxidation

  9. Growth of extrapulmonary tumours after inhalation of small doses of plutonium oxide by rats

    International Nuclear Information System (INIS)

    Nolibe, D.; Masse, R.; L'Hullier, I.; Metivier, H.; Lafuma, J.

    1983-01-01

    After inhalation of plutonium oxide ( 239 PuO 2 ) involving initial lung burdens ranging from 74 to 103 Bq, male rats of the Wistar strain are kept in conditions allowing maximum survival; tumour incidences for the target organ (lung) and for the rest of the organs are calculated separately after the death of the animals. In the outbred Wistar rat the incidence of lung tumours is 18.5% for an initial lung burden of 74 Bq. The mean survival time of animals having such tumours is 973 days after inhalation. For an initial burden of 103 Bq syngenetic Wistar AG rats show a lower frequency of lung tumours (6.1%), but also a much reduced mean survival time, namely 757 days. Compared with the frequencies observed in the corresponding control groups, the frequency of non-pulmonary tumours is twice as high (12%) in consanguineous rats and six times as high (25.9%) in conventional rats. A supralinear dose-effect relationship at very low doses seems improbable in view of the dose delivered ( -3 Gy in the most exposed organs, such as the liver) and, in particular, because there is no correlation between the dose delivered to the organs and the location of the tumours. The exposed animals show, on the one hand, no specificity of organs for the surplus extrapulmonary tumours observed, and on the other, an inhibition by about 45% in the natural cytotoxic activity (natural killers) measured one year after inhalation. These observations suggest the hypothesis that an anti-tumour control mechanism is affected, perhaps as a result of the irradiation experienced during the circulation of blood cells in the lung capillaries. The failure of this system would in that case allow the expression of neoplastic characters as ageing progresses. A non-specific BCG immunotherapy does not restore this anti-tumour control system. (author)

  10. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, S.S.; Lyerly, D.P. (Environmental Protection Agency, Research Triangle Park, NC (USA))

    1989-12-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with (35S)methionine and (3H)fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure.

  11. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    International Nuclear Information System (INIS)

    Padilla, S.S.; Lyerly, D.P.

    1989-01-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with [35S]methionine and [3H]fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure

  12. A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human.

    Science.gov (United States)

    Filser, Johannes Georg; Klein, Dominik

    2018-04-01

    Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum. Modeled ET metabolism is mediated by hepatic cytochrome P450 2E1, EO metabolism by hepatic microsomal epoxide hydrolase or cytosolic glutathione S-transferase in various tissues. EO is also spontaneously hydrolyzed or conjugated with glutathione. The model was validated on experimental data collected in mice, rats, and humans. Modeled were uptake by inhalation, wash-in-wash-out effect in the upper respiratory airways, distribution into tissues and organs, elimination via exhalation and metabolism, and formation of 2-hydroxyethyl adducts with hemoglobin and DNA. Simulated concentration-time courses of ET or EO in inhaled (gas uptake studies) or exhaled air, and of EO in blood during exposures to ET or EO agreed excellently with measured data. Predicted levels of adducts with DNA and hemoglobin, induced by ET or EO, agreed with reported levels. Exposures to 10000 ppm ET were predicted to induce the same adduct levels as EO exposures to 3.95 (mice), 5.67 (rats), or 0.313 ppm (humans). The model is concluded to be applicable for assessing health risks from inhalation exposure to ET or EO. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  13. Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

    Science.gov (United States)

    Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

    2008-07-01

    Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

  14. Late effects of inhaled 253Es(NO3)3 in rats

    International Nuclear Information System (INIS)

    Ballou, J.E.; Dagle, G.E.; Gies, R.A.; Smith, L.G.

    1979-01-01

    Einsteinium-253 nitrate was administered as an aerosol to male Wistar rats and the long-term biological effects were followed for the animals' life span. Lung was the major target organ for absorbed radiation dose and tumor induction, in agreement with results for other inhaled transuranic nitrates. The earlier finding of a high incidence of bone tumors following intratracheal instillation of 253 EsCl 3 was not confirmed in the present study with inhaled 253 Es(NO 3 ) 3 . The reason for the difference in bone tumor production is believed to be related to the different acute toxicities of intratracheally instilled and inhaled 253 Es. Intratracheally instilled 253 EsCl 3 was less acutely toxic (only a single lobe or one-half the lung was irradiated); thus, a larger more tumorigenic dose could be translocated to bone without shortening the life span to the extent that bone tumors could not be expressed. The radiation dose from inhaled 253 Es(NO 3 ) 3 was uniformly spread throughout both lungs and early death due to a generalized radiation pneumonitis precluded the development of long-term effects in bone. (author)

  15. Influence of initial lung deposit on pulmonary clearance after plutonium oxide inhalation in rat

    International Nuclear Information System (INIS)

    Van der Meeren, A.; Grillon, G.; Tourdes, F.; Rateau, S.; Le Gall, B.; Griffiths, N.

    2007-01-01

    Alveolar macrophages are a key element in the clearance of inhaled particles after phagocytosis, and thus participate actively in lung dose distribution and in the risk of tumour formation. We studied the influence of initial lung deposit (ILD) on lung clearance and distribution of activity from 3 d to 3 months after inhalation of two forms of PuO 2 (97% 239 Pu and 70% 239 Pu) in rats. ILDs ranging from 2.1 to 17 kBq were used. The total activity measured using X-ray spectrometry 3 months post-inhalation, relative to the ILD, showed a similar decrease in all groups, with the remaining activity representing ∼30% of the ILD. The total activity recovered in bronchoalveolar lavages represented ∼60% of the total lung activity. This ratio remained stable over time for the lowest ILD tested but decreased for higher ILD. In addition, the percentage of macrophages associated with particles decreased faster with time in rats with the highest ILD. Under our experimental conditions, there were no marked differences in lung clearance between groups. However, the distribution of the activity seems to vary with the time post-exposure between low and high ILD. (authors)

  16. Respiratory Effects of Inhaled Single-Walled Carbon Nanotubes: The Role of Particle Morphology and Iron Content

    Science.gov (United States)

    Madl, Amy Kathleen

    Nanotechnology provides promise for significant advancements in a number of different fields including imaging, electronics, and therapeutics. With worldwide production of carbon nanotubes (CNTs) exceeding over 500 metric tons annually and industry growth expecting to double over the next 5 yr, there are concerns our understanding of the hazards of these nanomaterials may not be keeping pace with market demand. The physicochemical properties of CNTs may delineate the key features that determine either toxicity or biocompatibility and assist in evaluating the potential health risks posed in industrial and consumer product settings. We hypothesized that the iron content and morphology of inhaled single-walled carbon nanotubes (SWCNTs) influences the extent of cellular injury and alters homeostasis in the lung. To address this hypothesis, (1) an aerosol system was developed to deliver carbon-based nanomaterials in a manner of exposure that is physiologically and environmentally relevant (e.g., inhalation), (2) acute (1 d) and subacute (10 d) nose-only inhalation studies to a well-characterized aerosol of iron-containing (FeSWCNT) versus cleaned (iron removed, cSWCNTs) SWCNTs were conducted to evaluate the time-course patterns of possible injury through measurement of markers of cytotoxicity, inflammation, and cellular remodeling/homeostasis, and (3) the effects of SWCNTs were compared to other well-studied materials (e.g. non-fibrous, low-iron content ultrafine carbon black and fibrous, high-iron content, highly persistent, durable and potent carcinogen crocidolite) to offer insights into the relative toxicity of these nanomaterials as well as the possible mechanisms by which the effects occur. Rats (SD) were exposed to either aerosolized SWCNTs (raw FeSWCNT or purified cSWCNT), carbon black (CB), crocidolite, or fresh air via nose-only inhalation. Markers of inflammation and cytotoxicity in lung lavage, mucin in different airway generations, and collagen in the

  17. Anthriscus nemorosa essential oil inhalation prevents memory impairment, anxiety and depression in scopolamine-treated rats.

    Science.gov (United States)

    Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian

    2016-12-01

    Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Absorption, distribution and excretion of inhaled hydrogen fluoride in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J.B.

    1979-01-01

    Rats were subjected to whole body HF exposure for 6 hrs or to nose-only HF exposure for 1 hr. Total and/or ionic fluoride concentrations in selected tissues were determined at various times following exposure. In rats sacrificed 6 hrs after whole body exposure, dose-dependent increases in lung, plasma, and kidney total and ionic fluoride concentration occurred. Rats excreted more fluoride in the urine after whole body exposure than could be explained by the amount of HF inhaled. Considerable evidence suggests that airborne HF deposits on fur and is then ingested due to preening activity. Urinary fluoride excretion was increased by nose-only exposure. The urinary fluoride excretion accounted for approximately twice the fluoride estimated to be inhaled during exposure. Tissue fluoride concentrations were elevated immediately after nose-only exposure. Fluoride concentrations in lung and kidney returned to control levels within 12 hrs. Plasma fluoride concentration was slightly elevated 24 hrs after the start of the 1 hr exposure but was at control levels at 96 hrs. Immediately following nose-only exposure, lung ionic fluoride concentrations were less than plasma ionic fluoride concentrations suggesting that the fluoride in the lung had reached that site via plasma transport rather than by inhalation. A dose-dependent increase in plasma ionic fluoride concentration occurred after upper respiratory tract HF exposure providing strong evidence that fluoride is absorbed systemically from that site. The plasma ionic fluoride concentration after upper respiratory tract exposure was of sufficient magnitude to account for the plasma fluoride concentrations observed in intact nose-only exposed rats. (ERB)

  19. Disposition of inhaled 1-chloro-2-propanol in F344/N rats

    International Nuclear Information System (INIS)

    Bond, J.A.; Birnbaum, L.S.; Dahl, A.R.; Medinsky, M.A.; Sabourin, P.J.; Henderson, R.F.

    1988-01-01

    Propylene chlorohydrins, of which 1-chloro-2-propanol (1-CP) is a constituent, used as intermediates in the manufacture of propylene oxide and have been identified as potential air pollutants. The objective of these studies was to determine whether changes in the inhaled exposure concentration would affect the disposition of 1-CP in rats. In addition, experiments were conducted to identify the carbon atom of 1-CP that is metabolized to CO2. Rats were exposed nose-only to [14C]1-CP for 6 hr to 8.3 +/- 1.0 ppm (26.1 +/- 3.2 micrograms/liter air) or 77 +/- 4 ppm (245 +/- 13 micrograms/liter air) (mean +/- SE). There were two major routes of elimination of 14C, urinary and exhalation of CO2, which together accounted for about 80% of the total 14C in excreta and carcass. Half-times for elimination of 14C in urine as 14CO2 were between 3 and 7 hr with no effect of exposure concentration on the elimination half-times for either route. After the end of exposure, kidneys, livers, trachea, and nasal turbinates contained high concentrations of [14C]1-CP equivalents at both exposure concentrations (30-50 nmol 14C/g tissue for the 8 ppm exposure level and 200-350 nmol 14C/g tissue for the 80 ppm exposure level). Elimination of 14C from tissues was biphasic with about 50% of the material in a tissue being rapidly eliminated with a half-time of 1 to 3 hr and the remaining material slowly eliminated with a half-time of 40 to 80 hr. There was no effect of exposure concentration on elimination half-times in tissues. Major metabolites detected in urine and tissues (liver, kidney, and lung) were N-acetyl-S-(hydroxypropyl)cysteine and/or S-(2-hydroxypropyl)-cysteine. Little unmetabolized 1-CP (less than 1%) was detected in analyzed tissues or urine

  20. Influence of preexisting pulmonary emphysema on susceptibility of rats to inhaled diesel exhaust

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Griffith, W.C.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K.

    1990-01-01

    The susceptibilities of normal rats and rats with preexisting pulmonary emphysema to chronically inhaled diesel exhaust were compared. Rats were exposed 7 h/day, 5 days/wk for 24 months to diesel exhaust at 3.5 mg soot/m3, or to clean air as controls. Emphysema was induced in one-half of the rats by intratracheal instillation of elastase 6 wk before exhaust exposure. Measurements included lung burdens of diesel soot, respiratory function, bronchoalveolar lavage, clearance of radiolabeled particles, pulmonary immune responses, lung collagen, excised lung weight and volume, histopathology, and mean linear intercept of terminal air spaces. Parameters indicated by analysis of variance to exhibit significant interactions between the influences of emphysema and exhaust were examined to determine if the effects were more than additive (indicating increased susceptibility). Although 14 of 63 parameters demonstrated emphysema-exhaust interactions, none indicated increased susceptibility. Less soot accumulated in lungs of emphysematous rats than in those of nonemphysematous rats, and the reduced accumulation had a sparing effect in the emphysematous rats. The results did not support the hypothesis that emphysematous lungs are more susceptible than are normal lungs to chronic exposure to high levels of diesel exhaust. The superimposition of effects of emphysema and exhaust, however, might still warrant special concern for heavy exposures of emphysematous subjects

  1. Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

    1995-12-01

    Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region.

  2. Induction of cancers in the rat after inhalation of alpha-emitting radionuclides

    International Nuclear Information System (INIS)

    Morin, M.; Nenot, J.C.; Masse, R.; Nolibe, D.; Metivier, H.; Lafuma, J.

    1976-01-01

    Experiments have been conducted for several years on the toxic action of inhaled alpha-emitters on laboratory rats. The inhaled radionuclides were 239 Pu, 238 Pu and 241 Am in oxide and nitrate form. The initial alveolar activities varied to give total activities ranging from 1 to 200 thousand million alpha-particles per gram of lung. Variations, depending on the physico-chemical form of the nuclides, in the space and time distributions of the dose are observed. The influence of the two parameters on life span reduction, latency time and frequency of cancer occurrence, initial location of tumours and their histological types were studied. A theoretical model relating the cancerogenous effect to the dose is compared with experimental data. (author)

  3. Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

    International Nuclear Information System (INIS)

    Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

    1995-01-01

    Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region

  4. Jet fuel kerosene is not immunosuppressive in mice or rats following inhalation for 28 days.

    Science.gov (United States)

    White, Kimber L; DeLorme, Michael P; Beatty, Patrick W; Smith, Matthew J; Peachee, Vanessa L

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet fuel kerosene on the immune system, in conjunction with an accurate, quantitative characterization of the aerosol and vapor exposure concentrations. Two female rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m(3) for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were subsequently evaluated. No marked effects were observed in either species on body weights, spleen or thymus weights, the T-dependent antibody-forming cell response (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few exceptions, spleen cell numbers and phenotypes were also unaffected. Natural killer (NK) cell activity in mice was unaffected, while the NK assessment in rats was not usable due to an unusually low response in all groups. These studies demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000 mg/m(3) did not adversely affect the functional immune responses of female mice and rats.

  5. Impaired mitochondrial respiration and protein nitration in the rat hippocampus after acute inhalation of combustion smoke

    International Nuclear Information System (INIS)

    Lee, Heung M.; Reed, Jason; Greeley, George H.; Englander, Ella W.

    2009-01-01

    Survivors of massive inhalation of combustion smoke endure critical injuries, including lasting neurological complications. We have previously reported that acute inhalation of combustion smoke disrupts the nitric oxide homeostasis in the rat brain. In this study, we extend our findings and report that a 30-minute exposure of awake rats to ambient wood combustion smoke induces protein nitration in the rat hippocampus and that mitochondrial proteins are a sensitive nitration target in this setting. Mitochondria are central to energy metabolism and cellular signaling and are critical to proper cell function. Here, analyses of the mitochondrial proteome showed elevated protein nitration in the course of a 24-hour recovery following exposure to smoke. Mass spectrometry identification of several significantly nitrated mitochondrial proteins revealed diverse functions and involvement in central aspects of mitochondrial physiology. The nitrated proteins include the ubiquitous mitochondrial creatine kinase, F1-ATP synthase α subunit, dihydrolipoamide dehydrogenase (E3), succinate dehydrogenase Fp subunit, and voltage-dependent anion channel (VDAC1) protein. Furthermore, acute exposure to combustion smoke significantly compromised the respiratory capacity of hippocampal mitochondria. Importantly, elevated protein nitration and reduced mitochondrial respiration in the hippocampus persisted beyond the time required for restoration of normal oxygen and carboxyhemoglobin blood levels after the cessation of exposure to smoke. Thus, the time frame for intensification of the various smoke-induced effects differs between blood and brain tissues. Taken together, our findings suggest that nitration of essential mitochondrial proteins may contribute to the reduction in mitochondrial respiratory capacity and underlie, in part, the brain pathophysiology after acute inhalation of combustion smoke

  6. Effect of age on the metabolism of inhaled beryllium fluoride in rats

    Energy Technology Data Exchange (ETDEWEB)

    Moskalev, Yu.I.; Bugryshev, P.F.; Zaikina, T.I. (Ministry of Health, Moscow (USSR). Inst. of Biophysics)

    1988-01-01

    The studies reported here investigated age-related differences in the distribution of {sup 7}Be following a single inhalation of carrier-free {sup 7}BeF{sub 2} by rats. Age greatly affected the amount of {sup 7}BeF{sub 2} deposited in each region of the respiratory system, the rate of beryllium translocation from the upper respiratory tract and oral cavity to the stomach, its retention in each section of the gastrointestinal tract, the distribution pattern and the routes of removal. (author).

  7. Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

    Science.gov (United States)

    Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

    2003-01-01

    This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

  8. Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

    OpenAIRE

    Rydman, Elina M.; Ilves, Marit; Koivisto, Antti J.; Kinaret, Pia A. S.; Fortino, Vittorio; Savinko, Terhi S.; Lehto, Maili T.; Pulkkinen, Ville; Vippola, Minnamari; Hämeri, Kaarle J.; Matikainen, Sampsa; Wolff, Henrik; Savolainen, Kai M.; Greco, Dario; Alenius, Harri

    2014-01-01

    Background Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic dise...

  9. Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

    Science.gov (United States)

    Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

    2013-01-01

    Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

  10. Impact of gasoline inhalation on some neurobehavioural characteristics of male rats

    Science.gov (United States)

    2009-01-01

    Background This paper examines closely and compares the potential hazards of inhalation of two types of gasoline (car fuel). The first type is the commonly use leaded gasoline and the second is the unleaded type enriched with oxygenate additives as lead substituent in order to raise the octane number. The impacts of gasoline exposure on Na+, K+-ATPase, superoxide dismutase (SOD), acetylcholinesterase (AChE), total protein, reduced glutathione (GSH), and lipid peroxidation (TBARS) in the cerebral cortex, and monoamine neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the cerebral cortex, hippocampus, cerebellum and hypothalamus were evaluated. The effect of gasoline exposure on the aggressive behaviour tests was also studied. Results The present results revealed that gasoline inhalation induced significant fluctuations in the levels of the monoamine neurotransmitters in the studied brain regions. This was concomitant with a decrease in Na+, K+-ATPase activity and total protein content. Moreover, the group exposed to the unleaded gasoline exhibited an increase in lipid peroxidation and a decrease in AChE and superoxide dismutase activities. These physiological impairments were accompanied with a higher tendency towards aggressive behaviour as a consequence to gasoline inhalation. Conclusion It is concluded from the present work that chronic exposure to either the leaded or the unleaded gasoline vapours impaired the levels of monoamine neurotransmitters and other biochemical parameters in different brain areas and modulated several behavioural aspects related to aggression in rats. PMID:19930677

  11. Impact of gasoline inhalation on some neurobehavioural characteristics of male rats.

    Science.gov (United States)

    Kinawy, Amal A

    2009-11-24

    This paper examines closely and compares the potential hazards of inhalation of two types of gasoline (car fuel). The first type is the commonly use leaded gasoline and the second is the unleaded type enriched with oxygenate additives as lead substituent in order to raise the octane number. The impacts of gasoline exposure on Na+, K+-ATPase, superoxide dismutase (SOD), acetylcholinesterase (AChE), total protein, reduced glutathione (GSH), and lipid peroxidation (TBARS) in the cerebral cortex, and monoamine neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the cerebral cortex, hippocampus, cerebellum and hypothalamus were evaluated. The effect of gasoline exposure on the aggressive behaviour tests was also studied. The present results revealed that gasoline inhalation induced significant fluctuations in the levels of the monoamine neurotransmitters in the studied brain regions. This was concomitant with a decrease in Na+, K+-ATPase activity and total protein content. Moreover, the group exposed to the unleaded gasoline exhibited an increase in lipid peroxidation and a decrease in AChE and superoxide dismutase activities. These physiological impairments were accompanied with a higher tendency towards aggressive behaviour as a consequence to gasoline inhalation. It is concluded from the present work that chronic exposure to either the leaded or the unleaded gasoline vapours impaired the levels of monoamine neurotransmitters and other biochemical parameters in different brain areas and modulated several behavioural aspects related to aggression in rats.

  12. Impact of gasoline inhalation on some neurobehavioural characteristics of male rats

    Directory of Open Access Journals (Sweden)

    Kinawy Amal A

    2009-11-01

    Full Text Available Abstract Background This paper examines closely and compares the potential hazards of inhalation of two types of gasoline (car fuel. The first type is the commonly use leaded gasoline and the second is the unleaded type enriched with oxygenate additives as lead substituent in order to raise the octane number. The impacts of gasoline exposure on Na+, K+-ATPase, superoxide dismutase (SOD, acetylcholinesterase (AChE, total protein, reduced glutathione (GSH, and lipid peroxidation (TBARS in the cerebral cortex, and monoamine neurotransmitters dopamine (DA, norepinephrine (NE and serotonin (5-HT in the cerebral cortex, hippocampus, cerebellum and hypothalamus were evaluated. The effect of gasoline exposure on the aggressive behaviour tests was also studied. Results The present results revealed that gasoline inhalation induced significant fluctuations in the levels of the monoamine neurotransmitters in the studied brain regions. This was concomitant with a decrease in Na+, K+-ATPase activity and total protein content. Moreover, the group exposed to the unleaded gasoline exhibited an increase in lipid peroxidation and a decrease in AChE and superoxide dismutase activities. These physiological impairments were accompanied with a higher tendency towards aggressive behaviour as a consequence to gasoline inhalation. Conclusion It is concluded from the present work that chronic exposure to either the leaded or the unleaded gasoline vapours impaired the levels of monoamine neurotransmitters and other biochemical parameters in different brain areas and modulated several behavioural aspects related to aggression in rats.

  13. Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters.

    Science.gov (United States)

    Keenan, C M; Kelly, D P; Bogdanffy, M S

    1990-08-01

    Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE.

  14. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yeon Soo [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Chung, Myung Hee [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)]. E-mail: mhchung@catholic.ac.kr; Park, Seog Hee [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Kim, Hyeon-Yeong [Industrial Chemicals Research Center, Industrial Safety and Health Research Institute KISCO, 104-8, Moonji-dong, Yusong-gu, Taejon-si 305-380 (Korea, Republic of); Choi, Byung Gil [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Lim, Hyun Wook [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Kim, Jin Ah [Department of Pathology, Holy Family Hospital, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon-si, Kyung gi-do 420-717 (Korea, Republic of); Yoo, Won Jong [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)

    2007-05-15

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 {+-} 32.82 HU, 3 ppm: -720.65 {+-} 34.21 HU, 6 ppm: -756.41 {+-} 41.68 HU, 12 ppm: -812.56 {+-} 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow

  15. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    International Nuclear Information System (INIS)

    Lim, Yeon Soo; Chung, Myung Hee; Park, Seog Hee; Kim, Hyeon-Yeong; Choi, Byung Gil; Lim, Hyun Wook; Kim, Jin Ah; Yoo, Won Jong

    2007-01-01

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 ± 32.82 HU, 3 ppm: -720.65 ± 34.21 HU, 6 ppm: -756.41 ± 41.68 HU, 12 ppm: -812.56 ± 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow-up study, the

  16. Pulmonary and cardiovascular responses of rats to inhalation of silver nanoparticles.

    Science.gov (United States)

    Roberts, Jenny R; McKinney, Walter; Kan, Hong; Krajnak, Kristine; Frazer, David G; Thomas, Treye A; Waugh, Stacey; Kenyon, Allison; MacCuspie, Robert I; Hackley, Vincent A; Castranova, Vincent

    2013-01-01

    Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 μg/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 μg/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 μg Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

  17. Effects and Mechanism of SO2 Inhalation on Rat Myocardial Collagen Fibers.

    Science.gov (United States)

    Chen, Ping; Qiao, Decai; Liu, Xiaoli

    2018-03-21

    BACKGROUND This study investigates the effects and mechanism of sulfur dioxide (SO2) inhalation and exercise on rat myocardial collagen fiber. MATERIAL AND METHODS The rats were randomly divided into 4 groups: a control group (RG), an exercise group (EG), an SO2 pollution group (SRG), and an SO2 pollution and exercise group (SEG). Body weight, cardiac index, and left ventricular index in each group were compared. The myocardial hydroxyproline (Hyp) concentration was determined by pepsin acid hydrolysis. The interstitial myocardial collagen expression was measured by Sirius Red F3B in saturated carbazotic acid. The local myocardial angiotensin II type 1 receptor (AT1R) and connective tissue growth factor (CTGF) expression was tested by immunohistochemistry SABC method. RESULTS Compared with RG, the weight growth rate of EG, SRG, and SEG decreased significantly (PSO2 inhalation and exercise will not only offset beneficial health effects of movement on the cardiovascular system, but also produce more unfavorable influences. People should pay attention to their environment when exercising, and try to avoid exercising in environments with SO2 pollution.

  18. Dose patterns for 106RuO4 inhaled by Fischer-344 rats and Beagle dogs

    International Nuclear Information System (INIS)

    Runkle, G.E.; Snipes, M.B.

    1978-01-01

    Ruthenium-106 is an abundant fission product radionuclide in the nuclear fuel cycle which has potential for release as ruthenium tetroxide. Ruthenium tetroxide is a vapor, diffuses rapidly through air and porous materials, is chemically reactive and is rapidly reduced by any organic material to the dioxide form. Current ICRP recommendations consider the lung and gastrointestinal tract as critical organs for inhaled particles of radioactive ruthenium. This study was designed to provide additional data needed to adequately assess the risk for humans potentially exposed to 106 Ru encountered in this vapor form. Fischer-344 rats and Beagle dogs were given a nose-only exposure to 106 RuO 4 vapor to determine its distribution and retention patterns. The largest percentage of the initial body burden was found in the nasopharyngeal region of the respiratory tract. Less than 1% of the initial body burden was deposited in the pulmonary region. Most of the 106 Ru was cleared via the feces. A biomathematical simulation model was developed to fit the tissue and excreta data from the rat. This model was used to assess the short-term and long-term risks after inhalation of 106 RuO 4 . The observed deposition, retention and dose patterns for ruthenium tetroxide indicate the nasopharyngeal region should be considered as a critical region when considering the consequences of human exposure to this vapor

  19. Old age and gender influence the pharmacokinetics of inhaled manganese sulfate and manganese phosphate in rats

    International Nuclear Information System (INIS)

    Dorman, David C.; McManus, Brian E.; Marshall, Marianne W.; James, R. Arden; Struve, Melanie F.

    2004-01-01

    In this study, we examined whether gender or age influences the pharmacokinetics of manganese sulfate (MnSO 4 ) or manganese phosphate (as the mineral form hureaulite). Young male and female rats and aged male rats (16 months old) were exposed 6 h day -1 for 5 days week -1 to air, MnSO 4 (at 0.01, 0.1, or 0.5 mg Mn m -3 ), or hureaulite (0.1 mg Mn m -3 ). Tissue manganese concentrations were determined in all groups at the end of the 90-day exposure and 45 days later. Tissue manganese concentrations were also determined in young male rats following 32 exposure days and 91 days after the 90-day exposure. Intravenous 54 Mn tracer studies were also performed in all groups immediately after the 90-day inhalation to assess whole-body manganese clearance rates. Gender and age did not affect manganese delivery to the striatum, a known target site for neurotoxicity in humans, but did influence manganese concentrations in other tissues. End-of-exposure olfactory bulb, lung, and blood manganese concentrations were higher in young male rats than in female or aged male rats and may reflect a portal-of-entry effect. Old male rats had higher testis but lower pancreas manganese concentrations when compared with young males. Young male and female rats exposed to MnSO 4 at 0.5 mg Mn m -3 had increased 54 Mn clearance rates when compared with air-exposed controls, while senescent males did not develop higher 54 Mn clearance rates. Data from this study should prove useful in developing dosimetry models for manganese that consider age or gender as potential sensitivity factors

  20. Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.

    Science.gov (United States)

    Chu, I; Poon, R; Valli, V; Yagminas, A; Bowers, W J; Seegal, R; Vincent, R

    2005-01-01

    The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible

  1. Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Michael R Wilson

    2010-07-01

    Full Text Available Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO using a mouse model of lipopolysaccharide (LPS-induced pulmonary inflammation.Mice were exposed to 0-500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow.When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40-50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space.Overall, these data confirm some protective role for inhaled CO during pulmonary inflammation, although this required a dose that produced carboxyhemoglobin values close to potentially toxic levels for humans, and increased lung permeability.

  2. The deposition, distribution and retention of inhaled 239PuO2 in the lungs of rats with pulmonary emphysema

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Damon, E.G.; Diel, J.H.; Hahn, F.F.

    1981-01-01

    Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled 239 PuO 2 in rats. (author)

  3. Inhaled corticosteroids inhibit substance P receptor expression in asthmatic rat airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Li Miao

    2012-12-01

    Full Text Available Abstract Background Neurokinins (NKs participate in asthmatic airway inflammation, but the effects of NKs on airway smooth muscle cells (ASMCs and those of corticosteroids on NKs are unknown. Methods To investigate the effect of budesonide on substance P (NK-1 receptor (NK-1R expression in the lung and ASMCs, 45 Wistar rats were randomly divided into three groups: control, asthmatic, and budesonide treatment. Aerosolized ovalbumin was used to generate the asthmatic rat model, and budesonide was administered after ovalbumin inhalation. On day 21, bronchial responsiveness tests, bronchoalveolar lavage, and cell counting were conducted. NK-1R protein expression in the lung was investigated by immunohistochemistry and image analysis. Primary rat ASMC cultures were established, and purified ASMCs of the fourth passage were collected for mRNA and protein studies via real-time RT-PCR, immunocytochemistry, and image analysis. Results NK-1R mRNA and protein expression in the budesonide treatment group rat’s lung and ASMCs were less than that in the asthmatic group but greater than that in the control group. Conclusions NK-1R is involved in the pathogenesis of asthma and that budesonide may downregulate the expression of NK-1R in the ASMCs and airways of asthmatic rats, which may alleviate neurogenic airway inflammation.

  4. In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

    Science.gov (United States)

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

    2012-01-01

    One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

  5. Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity.

    Directory of Open Access Journals (Sweden)

    Eric J Griez

    Full Text Available BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001. This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05. CONCLUSIONS/SIGNIFICANCE: CO(2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2 may be part of a protective system triggered by suffocation and acute metabolic distress.

  6. Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

    Science.gov (United States)

    Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

    1998-01-01

    The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate

  7. Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats.

    Science.gov (United States)

    Brandenberger, Christina; Hotchkiss, Jon A; Krieger, Shannon M; Pottenger, Lynn H; Harkema, Jack R

    2015-11-05

    This study investigated the time- and concentration-dependent effects of inhaled ethylene on eosinophilic rhinitis and nasal epithelial remodeling in Fisher 344 rats exposed to 0, 10, 50, 300, or 10,000 ppm ethylene, 6 h/day, 5 days/week for up to 4 weeks. Morphometric quantitation of eosinophilic inflammation and mucous cell metaplasia/hyperplasia (MCM) and nasal mucosal gene expression were evaluated at anatomic sites previously shown to undergo ethylene-induced epithelial remodeling. Serum levels of total IgE, IgG1 and IgG2a were measured to determine if ethylene exposure increased the expression of Th2-associated (IgE and IgG1) relative to Th1-associated (IgG2a) antibody isotypes. Rats exposed to 0 or 10,000 ppm for 1, 3, 5, 10, or 20 days were analyzed to assess the temporal pattern of ethylene-induced alterations in nasal epithelial cell proliferation, morphology and gene expression. Rats exposed to 0, 10, 50, 300, and 10,000 ppm ethylene for 20 days were analyzed to assess concentration-dependent effects on lesion development. Additional rats exposed 4 weeks to 0, 300, or 10,000 ppm ethylene were held for 13 weeks post-exposure to examine the persistence of ethylene-induced mucosal alterations. The data indicate that cell death and reparative cell proliferation were not a part of the pathogenesis of ethylene-induced nasal lesions. Enhanced gene expression of Th2 cytokines (e.g., IL-5, IL-13) and chitinase (YM1/2) in the nasal mucosa was much greater than that of Th1 cytokines (e.g., IFNγ) after ethylene exposure. A significant increase in MCM was measured after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure 10 ppm ethylene. Ethylene-induced MCM was reversible after cessation of exposure. No increase in total serum IgE, IgG1 or IgG2a was measured in any ethylene-exposed group. These data do not support involvement of an immune-mediated allergic mechanism in the pathogenesis of ethylene-induced nasal lesions in rats. Repeated

  8. Modifying effects of preexisting pulmonary fibrosis on biological responses of rats to inhaled 239PuO2

    International Nuclear Information System (INIS)

    Lundgren, D.L.; Mauderly, J.L.; Rebar, A.H.; Gillett, N.A.; Hahn, F.F.

    1991-01-01

    We investigated the modifying effects of preexisting, bleomycin-induced pulmonary fibrosis on the deposition, retention, and biological effects of inhaled 239PuO2 in the rat. Among rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kilogram body mass were similar whether or not pulmonary fibrosis was present. However, clearance of 239Pu from the lungs was significantly decreased in the rats with preexisting pulmonary fibrosis. The incidence of lung lesions (epithelial hyperplasia, diffuse macrophage increases and aggregation, and loose and dense connective tissue) was significantly greater among rats with preexisting pulmonary fibrosis than among the exposed controls. Rats with preexisting fibrosis had shorter life spans than 239PuO2-exposed control rats. When groups of rats with similar alpha doses to the lungs were compared, the incidences of neoplastic lesions in the lung, the times to death of rats with lung neoplasms, and the risk of lung tumors per unit of alpha dose to the lungs in rats with or without pulmonary fibrosis were similar. The results of this study suggest that humans with uncomplicated pulmonary fibrosis may not be more sensitive to the carcinogenic effects of inhaled 239PuO2 than are individuals with normal lungs, assuming that the total alpha doses to the lungs are similar

  9. Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

    Science.gov (United States)

    Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

    2009-01-01

    The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

  10. Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

    Science.gov (United States)

    Kent, Marc; Creevy, Kate E; Delahunta, Alexander

    2010-01-01

    Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

  11. Late effects of inhaled 253Es(NO3)3 in the rat

    International Nuclear Information System (INIS)

    Ballou, J.E.; Smith, L.G.; Dagle, G.E.; Gies, R.A.

    1979-01-01

    The lungs of rats exposed to 253 Es(NO 3 ) 3 aerosols sustained the greatest cumulative radiation dose, approximately 6-fold higher than the skeletal dose. Malignant lung tumors (incidence 8.5, 27.6%) were observed after a mean cumulative lung dose of 26 and 400 rad, respectively. Higher lung doses were associated with severe life shortening that precluded the expression of delayed effects. Osteosarcomas of the skeleton (incidence 6.9%) were found after a mean cumulative skeletal dose of 68 rad. Earlier studies, which showed a high incidence of bone tumors and relatively fewer lung tumors after intratracheal instillation of 253 EsCl 3 , were not confirmed in this study with inhaled 253 Es(NO 3 ) 3

  12. Effect of day/night administration of three different inhalational anesthetics on melatonin levels in rats.

    Science.gov (United States)

    Ocmen, Elvan; Erdost, Hale Aksu; Duru, Leyla S; Akan, Pinar; Cimrin, Dilek; Gokmen, Ali N

    2016-06-01

    The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 am and 1:00 pm (day groups) or 7:00 pm and 1:00 am (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17±12.95 for control, 59.79±27.83 for isoflurane, 50.75±34.28 for sevoflurane and 212.20±49.56 pg/mL for desflurane groups. The night groups' mean melatonin levels were 136.12±33.20 for control, 139.85±56.29 for isoflurane, 117.48±82.39 for sevoflurane and 128.70±44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 am and 1:00 pm significantly increased melatonin levels (p0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p=0.718 and p>0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia. Copyright © 2016. Published by Elsevier Taiwan.

  13. Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Winkler-Heil, R.; Hofmann, W. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Hussain, M. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Higher Education Commission of Pakistan, Islamabad (Pakistan)

    2015-05-15

    Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM{sup -1}. If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas. (orig.)

  14. Quantitative biokinetic analysis of radioactively labelled, inhaled Titanium dioxide Nanoparticles in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Kreyling, Wolfgang G.; Wenk, Alexander; Semmler-Behnke, Manuela [Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH (Germany). Inst. fuer Lungenbiologie und Erkrankungen, Netzwerk Nanopartikel und Gesundheit

    2010-09-15

    The aim of this project was the determination of the biokinetics of TiO{sub 2} nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract - either via inhalation or instillation. We developed an own methodology to freshly synthesize and aerosolize TiO{sub 2}-NP in our lab for the use of inhalation studies. These NP underwent a detailed physical and chemical characterization providing pure polycrystalline anatase TiO{sub 2}-NP of about 20 nm (geometric standard deviation 1.6) and a specific surface area of 270 m{sup 2}/g. In addition, we developed techniques for sufficiently stable radioactive {sup 48}V labelling of the TiO{sub 2} NP. The kinetics of solubility of {sup 48}V was thoroughly determined. The methodology of quantitative biokinetics allows for a quantitative balance of the retained and excreted NP in control of the administered NP dose and provides a much more precise determination of NP fractions and concentrations of NP in organs and tissues of interest as compared to spotting biokinetics studies. Small fractions of TiO{sub 2}-NP translocate across the air-blood-barrier and accumulate in secondary target organs, soft tissue and skeleton. The amount of translocated TiO{sub 2}-NP is approximately 2% of TiO{sub 2}-NP deposited in the lungs. A prominent fraction of these translocated TiO{sub 2}-NP was found in the remainder. Smaller amounts of TiO{sub 2}-NP accumulate in secondary organs following particular kinetics. TiO{sub 2}-NP translocation was grossly accomplished within the first 2-4 hours after inhalation followed by retention in all organs and tissues studied without any detectable clearance of these biopersistent TiO{sub 2}-NP within 28 days. Therefore, our data suggest crossing of the air-blood-barrier of the lungs and subsequent accumulation in secondary organs and tissues depends on the NP material and its physico-chemical properties. Furthermore, we extrapolate that during repeated or chronic

  15. Quantitative biokinetic analysis of radioactively labelled, inhaled Titanium dioxide Nanoparticles in a rat model

    International Nuclear Information System (INIS)

    Kreyling, Wolfgang G.; Wenk, Alexander; Semmler-Behnke, Manuela

    2010-01-01

    The aim of this project was the determination of the biokinetics of TiO 2 nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract - either via inhalation or instillation. We developed an own methodology to freshly synthesize and aerosolize TiO 2 -NP in our lab for the use of inhalation studies. These NP underwent a detailed physical and chemical characterization providing pure polycrystalline anatase TiO 2 -NP of about 20 nm (geometric standard deviation 1.6) and a specific surface area of 270 m 2 /g. In addition, we developed techniques for sufficiently stable radioactive 48 V labelling of the TiO 2 NP. The kinetics of solubility of 48 V was thoroughly determined. The methodology of quantitative biokinetics allows for a quantitative balance of the retained and excreted NP in control of the administered NP dose and provides a much more precise determination of NP fractions and concentrations of NP in organs and tissues of interest as compared to spotting biokinetics studies. Small fractions of TiO 2 -NP translocate across the air-blood-barrier and accumulate in secondary target organs, soft tissue and skeleton. The amount of translocated TiO 2 -NP is approximately 2% of TiO 2 -NP deposited in the lungs. A prominent fraction of these translocated TiO 2 -NP was found in the remainder. Smaller amounts of TiO 2 -NP accumulate in secondary organs following particular kinetics. TiO 2 -NP translocation was grossly accomplished within the first 2-4 hours after inhalation followed by retention in all organs and tissues studied without any detectable clearance of these biopersistent TiO 2 -NP within 28 days. Therefore, our data suggest crossing of the air-blood-barrier of the lungs and subsequent accumulation in secondary organs and tissues depends on the NP material and its physico-chemical properties. Furthermore, we extrapolate that during repeated or chronic exposure to insoluble NP the translocated fraction of NP will

  16. Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.

    Science.gov (United States)

    Griffiths, N M; Van der Meeren, A; Fritsch, P; Abram, M-C; Bernaudin, J-F; Poncy, J L

    2010-09-01

    Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.

  17. Influence of elastase-induced emphysema and the inhalation of an irritant aerosol on deposition and retention of an inhaled insoluble aerosol in Fischer-344 rats

    International Nuclear Information System (INIS)

    Damon, E.G.; Mokler, B.V.; Jones, R.K.

    1983-01-01

    The purpose of this study was to assess the effects of elastase-induced pulmonary emphysema and the inhalation of an irritant aerosol (Triton X-100, a nonionic surfactant similar to those used in a number of pressurized consumer products) on pulmonary deposition and retention of an insoluble test aerosol, 59 FE-labeled Fe 2 O 3 . Untreated rats or rats pretreated by intratracheal in stillation with elastase were exposed to an aerosol of 59 Fe-labeled Fe 2 O 3 either 18 hr or 7 days after exposure to aerosslized Triton X-100 which was administered in doses of 20, 100, or 200 μg/g of lung. Rats pretreated with elastase had significantly lower pulmonary deposition of 59 Fe than the untreated controls (p 2 O 3 was unaffected by pretreatment with Triton X-100. Elastase treatment alone had no effect on retention of Fe 2 O 3 . Triton X-100 administered 18 hr prior to exposure of rats to Fe 2 O 3 aerosol resulted in dose-related increases in whole-body retention of 59 Fe. When rats were exposed to Triton X-100 7 days before exposure to Fe 2 O 3 , increased retention of 59 Fe was noted only in those treated at the highest Triton X-100 dose level (200 μg/g). 20 references, 5 tables

  18. Biological action of 239Pu during its administration to rats by inhalation and Zn- or CaDTPA- complexone therapy

    International Nuclear Information System (INIS)

    Sinyakov, E.G.; Nifatov, A.P.; Lyubchanskij, Eh.R.; Bazhin, A.G.

    1988-01-01

    The authors described the effect of substantial amounts of plutonium nitrate administered to rats by inhalation in the presence of Zn- or CaDTPA-complexone therapy for 2 months. A 2-fold decrease of absorbed doses in the lung, a 3-fold decrease in the skeleton and a 4-fold decrease in the liver were shown. The mean life span of the treated animals was considerably raised. A significant reduction of the frequency of development of severe pneumosclerosis and an increase in the frequency of lung tumor development were noted. In view of the above, complexone therapy should be necessarily recommended during inhalation of radionucleides in austantial ammounts

  19. Exposure of F344 rats to aerosols of 239PuO2 and chronically inhaled cigarette smoke

    International Nuclear Information System (INIS)

    Finch, G.L.; Nikula, K.J.; Barr, E.B.; Bechtold, W.E.; Chen, B.T.; Griffith, W.C.; Hobbs, C.H.; Hoover, M.D.; Mauderly, J.L.

    1994-01-01

    Nuclear workers may be accidently exposed to radioactive materials such as 239 PuO 2 by inhalation, and thus have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radionuclides and other carcinogens may increase the risk of cancer induction. An important and common lung carcinogen is cigarette smoke. This study is being conducted to better determine the combined effects of inhaled 239 PuO 2 and cigarette smoke on the induction of lung cancer in rats

  20. Time- and concentration-dependent genomic responses of the rat airway to inhaled nickel subsulfide

    Energy Technology Data Exchange (ETDEWEB)

    Efremenko, A.Y., E-mail: aefremenko@thehamner.org [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Campbell, J.L.; Dodd, D.E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Oller, A.R. [NiPERA, Inc., 2525 Meridian Parkway, Suite 240, Durham, NC 27713 (United States); Clewell, H.J. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2014-09-15

    Objective: To provide insights into the mode of action for Ni{sub 3}S{sub 2} lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Methods: Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni{sub 3}S{sub 2} at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m{sup 3} (0.03, 0.06, 0.11, and 0.44 mg Ni/m{sup 3}) for one and four weeks (6 h/day, 5 days/week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni{sub 3}S{sub 2} carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m{sup 3}, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 μg Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni{sub 3}S{sub 2} toxicity and carcinogenicity. - Highlights: • The mode of action for lung carcinogenicity of inhaled Ni{sub 3}S{sub 2} was investigated in rats. • Gene expression changes were determined in micro

  1. Time- and concentration-dependent genomic responses of the rat airway to inhaled nickel subsulfide

    International Nuclear Information System (INIS)

    Efremenko, A.Y.; Campbell, J.L.; Dodd, D.E.; Oller, A.R.; Clewell, H.J.

    2014-01-01

    Objective: To provide insights into the mode of action for Ni 3 S 2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Methods: Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni 3 S 2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m 3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m 3 ) for one and four weeks (6 h/day, 5 days/week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni 3 S 2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m 3 , for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 μg Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni 3 S 2 toxicity and carcinogenicity. - Highlights: • The mode of action for lung carcinogenicity of inhaled Ni 3 S 2 was investigated in rats. • Gene expression changes were determined in micro-dissected lung tissue at 1–4 weeks. • A non-genotoxic mode

  2. Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of plutonium from the rat

    International Nuclear Information System (INIS)

    Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

    1976-01-01

    After inhaling 1 to 4 HD (human dose equivalents, i.e. 1g of calcium trisodium N,N-bis(2-bis (carboxymethyl) amino ethyl)glycinate per 70kg of body weight) of Ca-DTPA, rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrified later than 3 weeks after the last exposure. Dogs were anesthetized and administered Ca-DTPA aerosols via an intratracheal catheter for 30min/day for 5 days. The average dose/exposure was 4 HD. One week after the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks post-exposure. Ephitheleal atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. In long-term studies, rats were administered a lung burden of about 78 nCi 239 Pu(NO 3 ) 4 by inhalation and 20 days later were given six inhalation treatments of about 1 HD Ca-DTPA. Over their lifetime these animals showed no difference in survival or bone or lung tumour incidence from rats receiving Pu alone. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months after the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed. (author)

  3. Inhalation developmental toxicology studies of 1,3-butadiene in the rat: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L.; Decker, J.R.; Evanoff, J.J.; Rommereim, R.L.; Rowe, S.E.; Westerberg, R.B.

    1987-11-01

    Maternal toxicity, reproductive performance and developmental toxicology were evaluated in Sprague-Dawley-derived rats during and following 6 hours/day, whole-body, inhalation exposures to 0, 40, 200, and 1000 ppM of 1,3-butadiene. The female rats (Ns = 24 to 28), which had mated with unexposed males, were exposed to the chemical from 6 through 15 dg and sacrificed on 20 dg. Maternal animals were weighed prior to mating and on 0, 6, 11, 16 and 20 dg; the rats were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. There were no significant differences among treatment groups in maternal body weights or extragestational weights of rats exposed to 1,3-butadiene concentrations of 40 or 200 ppM, but, in animals exposed to 1000 ppM, significantly depressed body weight gains were observed during the first 5 days of exposure and extragestational weight gains tended to be lower than control values. These results, and the absence of clinical signs of toxicity, were considered to indicate that there was no maternal toxicity at exposure levels of 200 ppM or lower. The percentage of pregnant animals and the number of litters with live fetuses were unaffected by treatment. Under the conditions of this exposure regimen, there was no evidence for a teratogenic response to 1,3-butadiene exposure.

  4. Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

    Science.gov (United States)

    Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

    2014-01-01

    The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

  5. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  6. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure

  7. Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

    Science.gov (United States)

    Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

    1989-03-01

    PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

  8. Cannabis sativa smoke inhalation decreases bone filling around titanium implants: a histomorphometric study in rats.

    Science.gov (United States)

    Nogueira-Filho, Getulio da R; Cadide, Tiago; Rosa, Bruno T; Neiva, Tiago G; Tunes, Roberto; Peruzzo, Daiane; Nociti, Francisco Humberto; César-Neto, João B

    2008-12-01

    Although the harmful effect of tobacco smoking on titanium implants has been documented, no studies have investigated the effects of cannabis sativa (marijuana) smoking. Thus, this study investigated whether marijuana smoke influences bone healing around titanium implants. Thirty Wistar rats were used. After anesthesia, the tibiae surface was exposed and 1 screw-shaped titanium implant was placed bilaterally. The animals were randomly assigned to one of the following groups: control (n = 15) and marijuana smoke inhalation (MSI) 8 min/d (n = 15). Urine samples were obtained to detect the presence of tetra-hidro-cannabinoid. After 60 days, the animals were killed. The degree of bone-to-implant contact and the bone area within the limits of the threads of the implant were measured in the cortical (zone A) and cancellous bone (zone B). Tetra-hidro-cannabinoid in urine was positive only for the rats of MSI group. Intergroup analysis did not indicate differences in zone A-cortical bone (P > 0.01), however, a negative effect of marijuana smoke (MSI group) was observed in zone B-cancellous bone for bone-to-implant contact and bone area (Student's t test, P smoke on bone healing may represent a new concern for implant success/failure.

  9. MTBE inhaled alone and in combination with gasoline vapor: uptake, distribution, metabolism, and excretion in rats.

    Science.gov (United States)

    Benson, J M; Barr, E B; Krone, J R

    2001-05-01

    The purpose of these studies was to extend previous evaluation of methyl tert-butyl ether (MTBE)* tissue distribution, metabolism, and excretion in rats to include concentrations more relevant to human exposure (4 and 40 ppm) and to determine the effects of coinhalation of the volatile fraction of unleaded gasoline on the tissue distribution, metabolism, and excretion of MTBE. Groups of male F344 rats were exposed nose-only for 4 hours to 4, 40, or 400 ppm 14C-MTBE or to 20 or 200 ppm of the light fraction of unleaded gasoline (LFG) containing 4 or 40 ppm 14C-MTBE, respectively. To evaluate the effects of repeated inhalation of LFG on MTBE tissue distribution, metabolism, and excretion, rats were exposed for 4 hours on each of 7 consecutive days to 20 or 200 ppm LFG with MTBE (4 or 40 ppm) followed on the eighth day by a similar exposure to LFG containing 14C-MTBE. Subgroups of rats were evaluated for respiratory parameters, initial body burdens, rates and routes of excretion, and tissue distribution and elimination. The concentrations of MTBE and its chief metabolite, tert-butyl alcohol (TBA), were measured in blood and kidney immediately after exposure, and the major urinary metabolites-2-hydroxyisobutyric acid (IBA) and 2-methyl-1,2-propanediol (2MePD)-were measured in urine. Inhalation of MTBE alone or as a component of LFG had no concentration-dependent effect on respiratory minute volume. The initial body burdens of MTBE equivalents achieved after 4 hours of exposure to MTBE did not increase linearly with exposure concentration. MTBE equivalents rapidly distributed to all tissues examined, with the largest percentages distributed to liver. The observed initial body burden did not increase linearly between 4 and 400 ppm. At 400 ppm, elimination half-times of MTBE equivalents from liver increased and from lung, kidney, and testes decreased compared with the two smaller doses. Furthermore, at 400 ppm the elimination half-time for volatile organic compounds (VOCs

  10. Behavioural effects of prenatal exposure to carbon disulphide and to aromatol in rats.

    Science.gov (United States)

    Lehotzky, K; Szeberényi, J M; Ungváry, G; Kiss, A

    1985-01-01

    The neurotoxic effects of prenatal organosolvent inhalation were studied in rats, because of the expectation that a developing organism may be more sensitive than the adult to the induction of functional deficits. The aim was to determine whether prenatal exposure to the new organosolvent mixture, Aromatol, and the well known neurotoxic carbon disulphide, would impair reflex ontogeny or produce neurobehavioural dysfunctions in the offspring. Development of gait, motor coordination, and activity, avoidance learning and swimming were tested in the offspring of CFY rat mothers, exposed to CS2 inhalation (0, less than 10, 700 and 2000 mg/m3) and to Aromatol (0, 600, 1000 and 2000 mg/m3) on days 7-15 gestation. Prenatal CS2 inhalation induced dose related perinatal mortality of pups. Eye opening and the auditory startle were retarded. There were immature gait, motor incoordination, diminished open field activity and altered behavioural patterns on day 21 and 36 but they were nearly age-appropriate on day 90. As signs of disturbed learning ability, there were diminished performance and lengthened latency of the conditioned avoidance response, related to the concentrations administered. Contrary to expectations, prenatal Aromatol inhalation had no effect on maturation of gait, behaviour patterns, or learning ability.

  11. Pulmonary effects after acute inhalation of oil dispersant (COREXIT EC9500A) in rats.

    Science.gov (United States)

    Roberts, Jenny R; Reynolds, Jeffrey S; Thompson, Janet A; Zaccone, Eric J; Shimko, Michael J; Goldsmith, William T; Jackson, Mark; McKinney, Walter; Frazer, David G; Kenyon, Allison; Kashon, Michael L; Piedimonte, Giovanni; Castranova, Vincent; Fedan, Jeffrey S

    2011-01-01

    COREXIT EC9500A (COREXIT) was used to disperse crude oil during the 2010 Deepwater Horizon oil spill. While the environmental impact of COREXIT has been examined, the pulmonary effects are unknown. Investigations were undertaken to determine whether inhaled COREXIT elicits airway inflammation, alters pulmonary function or airway reactivity, or exerts pharmacological effects. Male rats were exposed to COREXIT (mean 27 mg/m(3), 5 h). Bronchoalveolar lavage was performed on d 1 and 7 postexposure. Lactate dehydrogenase (LDH) and albumin were measured as indices of lung injury; macrophages, neutrophils, lymphocytes, and eosinophils were quantified to evaluate inflammation; and oxidant production by macrophages and neutrophils was measured. There were no significant effects of COREXIT on LDH, albumin, inflammatory cell levels or oxidant production at either time point. In conscious animals, neither breathing frequency nor specific airway resistance were altered at 1 hr, 1 d and 7 d postexposure. Airway resistance responses to methacholine (MCh) aerosol in anesthetized animals were unaffected at 1 and 7 d postexposure, while dynamic compliance responses were decreased after 1 d but not 7 d. In tracheal strips, in the presence or absence of MCh, low concentrations of COREXIT (0.001% v/v) elicited relaxation; contraction occurred at 0.003-0.1% v/v. In isolated, perfused trachea, intraluminally applied COREXIT produced similar effects but at higher concentrations. COREXIT inhibited neurogenic contractile responses of strips to electrical field stimulation. Our findings suggest that COREXIT inhalation did not initiate lung inflammation, but may transiently increase the difficulty of breathing.

  12. Dosimetry and response in rat pulmonary epithelium following inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Rhoads, K.; Mahaffey, J.A.; Sanders, C.L.

    1983-01-01

    The distribution of inhaled 239 PuO 2 and pathologic changes have been studied in the lung of rats. The clearance of inhaled 237 239 PuO 2 from the lung is a function of the amount of deposited Pu with a decrease in early alveolar clearance with increasing lung burden. With increasing time post-exposure there is a greater concentration of PuO 2 and an increased aggregation of PuO 2 particles in subpleural regions of the lung. Fibrotic and metaplastic lesions in the lung were usually focal, being found in subpleural regions associated with aggregates of PuO 2 . An average of 12 +- 6 percent of the lung volume was fibrotic at 530 days after an initial alveolar deposition of 180 nCi 239 Pu. Lung tumors occupied 4 +- 6 percent and epithelial metaplasias less than 1 percent of the lung volume at this time. Cell proliferation as assayed by tritiated thymidine autoradiography was greater in fibrotic, metaplastic and neoplastic regions than in areas of normal alveolar-bronchiolar epithelium. Turnover times ranged from about 6 days for fibrotic lesions to 1 to 3 days for metaplastic and neoplastic lesions. The lung tumor doubling times were 57 to 116 days due to tumor cell necrosis and other factors that limit tumor cell survival. Cell proliferation rates for adenomatous metaplasia were similar to those for adenocarcinoma while those for squamous cell metaplasia were similar to those for squamous cell carcinoma. Squamous lesions exhibited a more rapid growth than did adenomatous lesions

  13. Effects of 7.5% carbon dioxide inhalation on anxiety and mood in cigarette smokers.

    Science.gov (United States)

    Attwood, Angela S; Ataya, Alia F; Bailey, Jayne E; Lightman, Stafford L; Munafò, Marcus R

    2014-08-01

    Cigarette smoking is associated with elevated risk of anxiety and mood disorder. Using the 7.5% carbon dioxide (CO2) inhalation model of anxiety induction, we examined the effects of smoking status and abstinence from smoking on anxiety responses. Physiological and subjective responses to CO2 and medical air were compared in smokers and non-smokers (Experiment One) and in overnight abstinent and non-abstinent smokers (Experiment Two). CO2 induced greater increases in blood pressure in non-smokers compared with smokers (ps affect (p = 0.054) in non-abstinent compared with abstinent smokers. CO2 increased physiological and subjective indices of anxiety. There were differences across smoking groups indicating that the CO2 inhalation model is a useful tool for examining the relationship between smoking and anxiety. The findings suggested that both acute smoking and acute abstinence may protect against anxious responding. Further investigation is needed in long-term heavy smokers. © The Author(s) 2014.

  14. Inhaled Lavandula angustifolia essential oil inhibits consolidation of contextual- but not tone-fear conditioning in rats.

    Science.gov (United States)

    Coelho, Laura Segismundo; Correa-Netto, Nelson Francisco; Masukawa, Marcia Yuriko; Lima, Ariadiny Caetano; Maluf, Samia; Linardi, Alessandra; Santos-Junior, Jair Guilherme

    2018-04-06

    Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Deposition and retention patterns for 3-, 9-, and 15-micron latex microspheres inhaled by rats and guinea pigs

    International Nuclear Information System (INIS)

    Snipes, M.B.; Olson, T.R.; Yeh, H.C.

    1988-01-01

    This study was designed to determine the deposition patterns and fate of large particles inhaled by two species of small laboratory animals during nose breathing. Rats and guinea pigs inhaled 3-, 9-, or 15 micron polystyrene latex microspheres labeled with 46 Sc. Approximately 1.4% and 0.55% of the initial internally deposited body burden of 3-micron microspheres was in the alveolar region of the respiratory tract of rats and guinea pigs, respectively. None of the 9- or 15-micron microspheres were detected in the alveolar regions of the rats or guinea pigs. Ninety-five to 99% of the deposited microspheres cleared from these animals with biological half-times of 0.5-1.0 day. Most of the cleared radioactivity was in the feces. Approximations for long-term biological half-times for alveolar retention of the 3-micron microspheres were 63 days for rats and 83 days for guinea pigs. About 1% of the initial lung burden of 3-micron microspheres was translocated from lung to lung-associated lymph nodes in both species; none of the 9- or 15-micron microspheres were detected in those lymph nodes. Small fractions of the microspheres initially deposited in the airways of the head were retained with biological clearance half-times ranging from 9 to 350 days. Results from this study do not allow projections for deposition and retention patterns for similar particles inhaled by humans. Such projections must come from studies with humans, or from studies with animal species having deposition patterns for inhaled materials more comparable to those of humans

  16. A new approach combining analytical methods for workplace exposure assessment of inhalable multi-walled carbon nanotubes

    NARCIS (Netherlands)

    Tromp, P.C.; Kuijpers, E.; Bekker, C.; Godderis, L.; Lan, Q.; Jedynska, A.D.; Vermeulen, R.; Pronk, A.

    2017-01-01

    To date there is no consensus about the most appropriate analytical method for measuring carbon nanotubes (CNTs), hampering the assessment and limiting the comparison of data. The goal of this study is to develop an approach for the assessment of the level and nature of inhalable multi-wall CNTs

  17. The Effects of Inhaled Pimpinella peregrina Essential Oil on Scopolamine-Induced Memory Impairment, Anxiety, and Depression in Laboratory Rats.

    Science.gov (United States)

    Aydin, Emel; Hritcu, Lucian; Dogan, Gulden; Hayta, Sukru; Bagci, Eyup

    2016-11-01

    In the present study, we identified the effects of inhaled Pimpinella peregrina essential oil (1 and 3 %, for 21 continuous days) on scopolamine-induced memory impairment, anxiety, and depression in laboratory rats. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by means of the elevated plus-maze and forced swimming tests. The scopolamine alone-treated rats exhibited the following: decrease of the spontaneous alternation percentage in Y-maze test, increase of the number of working and reference memory errors in radial arm-maze test, along with decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Inhalation of the P. peregrina essential oil significantly improved memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. Our results suggest that the P. peregrina essential oil inhalation ameliorates scopolamine-induced memory impairment, anxiety, and depression. Moreover, studies on the P. peregrina essential oil may open a new therapeutic window for the prevention of neurological abnormalities closely related to Alzheimer's disease.

  18. Euthanasia of rats with carbon dioxide--animal welfare aspects.

    Science.gov (United States)

    Hackbarth, H; Küppers, N; Bohnet, W

    2000-01-01

    A method of inducing euthanasia by carbon dioxide (CO2) inhalation in the home cage of an animal is described and tested for distress by behavioural as well as by hormonal measures. The animals were maintained in their home cage while CO2 was induced at a flow of 6 l/min. The behaviour of the animals was measured continuously as were the serum concentrations of glucose, ACTH and corticosterone 30, 75 and 120 s after the CO2 was introduced into the cage. In order to test for distress, two groups of rats were pre-treated with acepromazine (orally) and pentobarbiturate (i.p. injection) respectively, in order to reduce possible distress caused by CO2 euthanasia, and were compared with control groups. There were no signs of distress by behavioural or by hormonal changes. All changes seen could be attributed to experimental effects and, especially as there was no difference between the pre-treated and the control groups of rats, it must be assumed that the described method of euthanasia is in concordance with animal welfare, it leads to rapid death without severe distress or pain, and it seems therefore to be 'humane'.

  19. Actinides behaviour after inhalation exposure of rats to industrial NpO2

    International Nuclear Information System (INIS)

    Ramounet, B.; Abram, M.C.; Rateau, G.; Grillon, G.; Fritsch, P.

    2000-01-01

    Preliminary results on 237 Np biological behaviour after inhalation exposure of rats to industrial NpO 2 have shown a skeletal retention of the actinides corresponding to about 1% of the Initial Lung Deposit (ILD). The powder contained both 237 Np and 238 Pu+ 239 Pu. The retention was measured by total alpha-counting in animals killed from 7 to 100 days post exposure (Lizon C. et al, IRPA 9, Avril 96, Vienne. 2, 451-453). The aim of this study was to provide dissolution parameters, fr and ss, of Np and Pu using a calculation method we have recently developed (Ramounet B. et al, Int. J. Radiat. Biol. 76(2), 215-222). A group of 30 male Sprague Dawley rats was exposed to NpO 2 aerosol (AMAD 2.6 μm, σg=2.2). The powder contained 77% of 237 Np, 2% of 239 Pu and 21% of 238 Pu in terms of alpha activity. The mean ILD of all rats, 0.5 kBq (σ=0.1), was measured 7 days post-exposure by in vivo X-ray measurement. Groups of 4 rats were sacrificed at 7, 30, 60, 90, 180, 270 and 365 days post-exposure. Liver, kidneys and femora were removed, heat mineralised and alpha sources were prepared after extractive chromatography. Alpha activities were measured by alpha-spectrometry. Up to 365 days, 80% of the ILD was cleared with a half time of about 60 days and the remaining with a half time of about 200 days. The dissolution parameters were estimated from the evolution of the skeletal and lung retention. f r values were about 1.10 -3 and s s about 1.10 -5 for the two actinides. From these results it appears that industrial NpO 2 look like a type S compound. However, the s s value we measured is about 10 times less than the default value described for type S. Experiments are in progress to confirm these dissolution parameter values in the case of high NpO 2 ILD altering lung clearance. (author)

  20. Pulmonary effects of inhaled limonene ozone reaction products in elderly rats.

    Science.gov (United States)

    Sunil, Vasanthi R; Laumbach, Robert J; Patel, Kinal J; Turpin, Barbara J; Lim, Ho-Jin; Kipen, Howard M; Laskin, Jeffrey D; Laskin, Debra L

    2007-07-15

    d-Limonene is an unsaturated volatile organic chemical found in cleaning products, air fresheners and soaps. It is oxidized by ozone to secondary organic aerosols consisting of aldehydes, acids, oxidants and fine and ultra fine particles. The lung irritant effects of these limonene ozone reaction products (LOP) were investigated. Female F344 rats (2- and 18-month-old) were exposed for 3 h to air or LOP formed by reacting 6 ppm d-limonene and 0.8 ppm ozone. BAL fluid, lung tissue and cells were analyzed 0 h and 20 h later. Inhalation of LOP increased TNF-alpha, cyclooxygenase-2, and superoxide dismutase in alveolar macrophages (AM) and Type II cells. Responses of older animals were attenuated when compared to younger animals. LOP also decreased p38 MAP kinase in AM from both younger and older animals. In contrast, while LOP increased p44/42 MAP kinase in AM from younger rats, expression decreased in AM and Type II cells from older animals. NF-kappaB and C/EBP activity also increased in AM from younger animals following LOP exposure but decreased or was unaffected in Type II cells. Whereas in younger animals LOP caused endothelial cell hypertrophy, perivascular and pleural edema and thickening of alveolar septal walls, in lungs from older animals, patchy accumulation of fluid within septal walls in alveolar sacs and subtle pleural edema were noted. LOP are pulmonary irritants inducing distinct inflammatory responses in younger and older animals. This may contribute to the differential sensitivity of these populations to pulmonary irritants.

  1. Pulmonary effects of inhaled limonene ozone reaction products in elderly rats

    International Nuclear Information System (INIS)

    Sunil, Vasanthi R.; Laumbach, Robert J.; Patel, Kinal J.; Turpin, Barbara J.; Lim, Ho-Jin; Kipen, Howard M.; Laskin, Jeffrey D.; Laskin, Debra L.

    2007-01-01

    d-Limonene is an unsaturated volatile organic chemical found in cleaning products, air fresheners and soaps. It is oxidized by ozone to secondary organic aerosols consisting of aldehydes, acids, oxidants and fine and ultra fine particles. The lung irritant effects of these limonene ozone reaction products (LOP) were investigated. Female F344 rats (2- and 18-month-old) were exposed for 3 h to air or LOP formed by reacting 6 ppm d-limonene and 0.8 ppm ozone. BAL fluid, lung tissue and cells were analyzed 0 h and 20 h later. Inhalation of LOP increased TNF-α, cyclooxygenase-2, and superoxide dismutase in alveolar macrophages (AM) and Type II cells. Responses of older animals were attenuated when compared to younger animals. LOP also decreased p38 MAP kinase in AM from both younger and older animals. In contrast, while LOP increased p44/42 MAP kinase in AM from younger rats, expression decreased in AM and Type II cells from older animals. NF-κB and C/EBP activity also increased in AM from younger animals following LOP exposure but decreased or was unaffected in Type II cells. Whereas in younger animals LOP caused endothelial cell hypertrophy, perivascular and pleural edema and thickening of alveolar septal walls, in lungs from older animals, patchy accumulation of fluid within septal walls in alveolar sacs and subtle pleural edema were noted. LOP are pulmonary irritants inducing distinct inflammatory responses in younger and older animals. This may contribute to the differential sensitivity of these populations to pulmonary irritants

  2. Risk analysis of fatal and incidental lung tumors in wister rats after inhalation of plutonium dioxide

    International Nuclear Information System (INIS)

    Kai, M.; Akahane, K.; Ogiso, Y.

    2000-01-01

    Cancer risk analysis was done in animal studies for inhalation of plutonium dioxide. Female Wister rats were exposed to an aerosol of plutonium with AMAD of 0.4-0.5 μm and followed up until they died. We made some model analyses using their likelihood function. This approach enables us to consider temporal variation in dose-response analysis. Each rat contributes to the total likelihood depending on fatal or incidental tumors. In Weibul model analysis, the logarithm of the hazard function can be linearly modeled with the term of log (dose), log-L model, and additional term of the square of log (dose), log-LQ model. The likelihood ratio statistics gave a significantly better fit of the log-LQ model. However, if data more than 4 Gy were excluded, there was no significant difference between both models. The ratio of hazard function at 1 Gy and 0 Gy, the excess relative risk, showed 30 for total tumors. This result was much different from those in PNL data (Sanders et al.). The difference of pulmonary deposition depending upon particle size would cause different tumor incidence. Our studies indicated significant increase of occurrence of fatal lung cancer at an average dose of 0.5 Gy and thus did not suggest that a life-span effective threshold for death was about 1 Gy to the lung, which is shown in some papers. In contrast PNL, the incidence of adenoma showing the maximum at 0.5 Gy decreased with increasing lung dose from 1.5 Gy or higher, where malignant tumors such as adenocarcinomas increased. This phenomenon was analyzed with carcinogenesis models. (author)

  3. Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

    Science.gov (United States)

    Hanas, Jay S; Bruce Briggs, G; Lerner, Megan R; Lightfoot, Stan A; Larabee, Jason L; Karsies, Todd J; Epstein, Robert B; Hanas, Rushie J; Brackett, Daniel J; Hocker, James R

    2010-05-01

    Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

  4. The effects of inhaled acetone on place conditioning in adolescent rats.

    Science.gov (United States)

    Lee, Dianne E; Pai, Jennifer; Mullapudui, Uma; Alexoff, David L; Ferrieri, Richard; Dewey, Stephen L

    2008-03-01

    Acetone is an ubiquitous ingredient in many household products (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is putatively abused; however, there is little empirical evidence to suggest that acetone alone has any abuse liability. Therefore, we systematically investigated the conditioned response to inhaled acetone in a place conditioning apparatus. Three groups of male, Sprague-Dawley rats were exposed to acetone concentrations of 5000, 10,000 or 20,000 ppm for 1 h in a conditioned place preference apparatus alternating with air for 6 pairing sessions. A place preference test ensued in an acetone-free environment. To test the preference of acetone as a function of pairings sessions, the 10,000 ppm group received an additional 6 pairings and an additional group received 3 pairings. The control group received air in both compartments. Locomotor activity was recorded by infrared photocells during each pairing session. We noted a dose response relationship to acetone at levels 5000-20,000 ppm. However, there was no correlation of place preference as a function of pairing sessions at the 10,000 ppm level. Locomotor activity was markedly decreased in animals on acetone-paired days as compared to air-paired days. The acetone concentrations we tested for these experiments produced a markedly decreased locomotor activity profile that resemble CNS depressants. Furthermore, a dose response relationship was observed at these pharmacologically active concentrations, however, animals did not exhibit a positive place preference.

  5. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    Fauran-Clavel, M.J.; Oustrin, J.; Godin, J.; Boudene, C.

    1982-01-01

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m 3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd ++ ion on the bone crystallization process [fr

  6. Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

    Science.gov (United States)

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; Lepera, José Salvador

    2013-03-01

    Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Copyright © 2013 Wiley Periodicals, Inc.

  7. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1988-08-01

    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

  8. Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of Pu from the rat

    International Nuclear Information System (INIS)

    Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

    1975-01-01

    After inhaling 1 to 4 HD (human dose equivalents, i.e., 1 g calcium trisodium N,N-bis (2-bis(carboxymethyl)amino) ethyl) glycinate/70 kg body weight) of Ca-DTPA rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrificed later than 3 weeks after the last exposure. Dogs were anesthetised and administered Ca-DTPA aerosols via an intratracheal catheter for 30 min/day for 5 days. The average dose/exposure was 4 HD. One week following the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks postexposure. Epithelial atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months following the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed

  9. Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure.

    Science.gov (United States)

    Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

    2017-01-01

    Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m 3 ), the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m 3 ) male group and 15% lower in the high (1.41 ± 0.71 mg/m 3 ) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m 3 .

  10. Biological effects of nano-nickel in rat lungs after administration by inhalation and by intratracheal instillation

    International Nuclear Information System (INIS)

    Ogami, A; Morimoto, Y; Murakami, M; Myojo, T; Oyabu, T; Tanaka, I

    2009-01-01

    We examined the biological effects of the nickel oxide (NiO) nanoparticles by inhalation and instillation study. Wistar male rats were exposed to NiO nanoparticles (nNiOs) for 4 weeks (6 hrs/day). The nNiOs was black-colored NiO (99.8%) and average particle size (APS) was 20 nm. The geometric mean diameter of the particles in the chamber and the daily average exposure concentration were 139 ± 12 nm and 1.0 ± 0.5 x 105 particles/cc, respectively. The deposited amount of nNiOs in the rat lungs at 4 days after the inhalation exposure ended was 29 ± 4 μg. Although nNiOs exposure group showed temporal significant increase in the number of total cells in brochoalveolar lavage fluid (BALF) at 4 days after the exposure end, the difference were not seen at one month after an exposure end compared with control group. The histopathological change was not severe just after the inhalation nor throughout the observation time. Elemental mappings of nickel showed that nickel particles were located in agglomeration at the pulmonary macrophages.

  11. Neurochemical Changes after Acute Binge Toluene Inhalation in Adolescent and Adult Rats: A High-Resolution Magnetic Resonance Spectroscopy Study

    Science.gov (United States)

    O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; McMechan, Andrew P.; Irtenkauf, Susan; Hannigan, John H.; Bowen, Scott E.

    2009-01-01

    Inhalant abuse in young people is a growing public health concern. We reported previously that acute toluene intoxication in young rats, using a pattern of exposures that approximate abuse patterns of inhalant use in humans, significantly altered neurochemical measures in select brain regions. In this study, adolescent and young adult rats were exposed similarly to an acute (2 × 15 min), high dose (8000 − 12000 ppm) of toluene and high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) was used to assess neurochemical profiles of tissue samples from a number of brain regions collected immediately following solvent exposure. The current investigation focused on N-acetyl-aspartate (NAA), choline-containing compounds, creatine, glutamate, GABA, and glutamine. Contrary to our predictions, no significant alterations were found in levels of NAA, choline, creatine, glutamate, or glutamine in adolescent animals. In contrast to these minimal effects in adolescents, binge toluene exposure altered several neurochemical parameters in young adult rats, including decreased levels of choline and GABA in the frontal cortex and striatum and lowered glutamine and NAA levels in the frontal cortex. One of the more robust findings was a wide-ranging increase in lactate after toluene exposure in adult animals, an effect not observed in adolescents. These age-dependent effects of toluene are distinct from those reported previously in juvenile rats and suggest a developmental difference in vulnerability to the effects of inhalants. Specifically, the results suggest that the neurochemical response to toluene in adolescents is attenuated compared to adults, and imply an association between these neurochemical differences and age-influenced differences in solvent abuse in humans. PMID:19628036

  12. The effects of inhaled acetone on place conditioning in adolescent rats

    Science.gov (United States)

    Lee, Dianne E.; Pai, Jennifer; Mullapudui, Uma; Alexoff, David L.; Ferrieri, Richard; Dewey, Stephen L.

    2009-01-01

    Introduction Acetone is a ubiquitous ingredient in many household products (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is putatively abused; however, there is little empirical evidence to suggest that acetone alone has any abuse liability. Therefore, we systematically investigated the conditioned response to inhaled acetone in a place conditioning apparatus. Method Three groups of male, Sprague-Dawley rats were exposed to acetone concentrations of 5,000, 10,000 or 20,000 ppm for 1 hour in a conditioned place preference apparatus alternating with air for 6 pairing sessions. A place preference test ensued in an acetone-free environment. To test the preference of acetone as a function of pairings sessions, the 10,000 ppm group received an additional 6 pairings and an additional group received 3 pairings. The control group received air in both compartments. Locomotor activity was recorded by infrared photocells during each pairing session. Results We noted a dose response relationship to acetone at levels 5,000-20,000 ppm. However, there was no correlation of place preference as a function of pairing sessions at the 10,000 ppm level. Locomotor activity was markedly decreased in animals on acetone-paired days as compared to air-paired days. Conclusion The acetone concentrations we tested for these experiments produced a markedly decreased locomotor activity profile that resemble CNS depressants. Furthermore, a dose response relationship was observed at these pharmacologically active concentrations, however, animals did not exhibit a positive place preference. PMID:18096214

  13. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  14. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    International Nuclear Information System (INIS)

    Clewell, H.J.; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-01-01

    , respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment

  15. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    Energy Technology Data Exchange (ETDEWEB)

    Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    , respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment.

  16. Tissue sensitivity of the rat upper and lower extrapulmonary airways to the inhaled electrophilic air pollutants diacetyl and acrolein.

    Science.gov (United States)

    Cichocki, Joseph A; Smith, Gregory J; Morris, John B

    2014-11-01

    The target site for inhaled vapor-induced injury often differs in mouth-breathing humans compared with nose-breathing rats, thus complicating the use of rat inhalation toxicity data for assessment of human risk. We sought to examine sensitivity of respiratory/transitional nasal (RTM) and tracheobronchial (TBM) mucosa to two electrophilic irritant vapors: diacetyl and acrolein. Computational fluid dynamic physiologically based pharmacokinetic modeling was coupled with biomarker assessment to establish delivered dose-response relationships in RTM and TBM in male F344 rats following 6 h exposure to diacetyl or acrolein. Biomarkers included glutathione status, proinflammatory and antioxidant gene mRNA levels, and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Modeling revealed that 0.0094-0.1653 μg acrolein/min-cm(2) and 3.9-21.6 μg diacetyl/min-cm(2) were deposited into RTM/TBM. Results indicate RTM and TBM were generally of similar sensitivity to diacetyl and acrolein. For instance, both tissues displayed induction of antioxidant and proinflammatory genes, and nuclear accumulation of Nrf2 after electrophile exposure. Hierarchical cellular response patterns were similar in RTM and TBM but differed between vapors. Specifically, diacetyl exposure induced proinflammatory and antioxidant genes concomitantly at low exposure levels, whereas acrolein induced antioxidant genes at much lower exposure levels than that required to induce proinflammatory genes. Generally, diacetyl was less potent than acrolein, as measured by maximal induction of transcripts. In conclusion, the upper and lower extrapulmonary airways are of similar sensitivity to inhaled electrophilic vapors. Dosimetrically based extrapolation of nasal responses in nose-breathing rodents may provide an approach to predict risk to the lower airways of humans during mouth-breathing. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All

  17. Effect of petroleum vapors inhalation on intestinal absorption of glucose and some amino acids in the rat

    International Nuclear Information System (INIS)

    Szablicka, E.; Oledzka, R.

    1989-01-01

    The proper intestinal absorption of nutrients, particularly sugars and amino acids, is necessary to keep the organism healthy. It is well known that various toxic compounds present in the environment can have an unfavorable influence. On the other hand it is also known that crude oil which pollutes the aqueous environment affects birds' gastrointestinal tract. Little is known about the influence of petroleum vapors on the gastrointestinal tract of animals and humans. The present study was undertaken to determine the effect of petroleum vapors inhalation on intestinal absorption of some nutrients (glucose, leucine, methionine) in rats

  18. Tissue distribution of a leukotriene antagonist 14C-LY170680, following inhalation exposure in the rat

    International Nuclear Information System (INIS)

    Pohland, R.C.; Beck, J.M.; Carlson, K.H.; Herman, D.R.; Hoppes, J.L.; Vavrek, M.T.; Wolff, R.K.

    1991-01-01

    Dissection and whole-body autoradiographic techniques were used to determine the tissue distribution profile of a leukotriene antagonist, 14 C-LY170680, following nose-only inhalation exposure in the rat. Liquid scintillation spectrometry and whole-body autoradiography indicated that highest concentrations of radiocarbon were present in stomach and small intestine at all time points. Radiocarbon reached maximum levels in stomach (2,259 ng-eq/g) and small intestine (2,399 ng-eq/g) 2 to 4 hours postexposure, respectively, and declined with time. In contrast, maximum radiocarbon concentrations in the head (146 ng-eq/g), trachea (408 ng-eq/g), and lung (534 ng-eq/g) occurred at 0 hours postexposure and steadily declined with time. Low concentrations of radiocarbon were detected in the liver ( 14 C-LY170680 were deposited in the head and within the lung following inhalation exposure. However, higher levels of radiocarbon present in the stomach and small intestine suggested significant nasal deposition followed by rapid clearance and ingestion of inhaled radioactive material. Distribution of radiocarbon limited to the respiratory and gastrointestinal tracts demonstrated minimal systemic absorption and exposure over the time course of this study

  19. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    Directory of Open Access Journals (Sweden)

    Felix Ulbrich

    Full Text Available Retinal ischemia and reperfusion injuries (IRI permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC of the rat's eye.IRI was performed on the left eyes of rats (n = 8 with or without inhaled Argon postconditioning (25, 50 and 75 Vol% for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours. Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001. Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01, as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001. Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

  20. Effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats

    Directory of Open Access Journals (Sweden)

    Zheng-guan WANG

    2015-04-01

    Full Text Available Objective To explore the protective effects of puerarin combined with edaravone on inhalation lung injury induced by black gunpowder smog in rats. Methods Forty healthy male Wistar rats were randomly divided into normal control group (group N, inhalation group (group X, puerarin group (group P, edaravone group (group E and edaravone combined with puerarin group (group L, with 8 rats in each group. Rat model of inhalation lung injury was reproduced by a self-made smoke generator. Rats in group E were given intraperitoneal injections of edaravone (9 mg/kg at 30 minutes and 1 day after modeling (twice totally. Rats in group P were given intraperitoneal injections of puerarin (100 mg/kg at 30 minutes and 1, 2, 3, 4, 5 days after modeling (6 times totally. Rats in group L were treated the way of both group E and P. The rats in group N and group X were given intraperitoneal injections of normal saline (12 ml/kg at the time-points above. The animals were sacrificed 6 days after modeling, and the blood samples were collected from abdominal aorta to assess arterial blood gas values, meanwhile the serum levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-10 (IL-10 were determined by ELISA. Lung tissue homogenates were prepared to determine the protein content and myeloperoxidase (MPO activity. The pathological changes in the lung tissue with HE staining were observed under light microscope. Results Arterial blood gas analysis revealed that the PaO2 levels in groups P, E and L were higher than that in group X (P<0.05, and the PaO2 levels in groups E and L were higher than that in group P (P<0.05, while the PaCO2 level in group L was lower than that in groups X and E (P<0.05. The TNF-α, IL-6 and IL-10 levels in serum, the protein content and MPO activity in lung tissue homogenate in groups P, E and L were lower than those of group X (P<0.05. The TNF-α and IL-6 levels in serum and protein content and MPO activity in lung

  1. Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.

    Science.gov (United States)

    Avella, Joseph; Kunaparaju, Naveen; Kumar, Sunil; Lehrer, Michael; Zito, S William; Barletta, Michael

    2010-09-01

    1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if

  2. Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

    Science.gov (United States)

    Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

    2002-09-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

  3. Inhaled /sup 147/Pm and/or total-body gamma radiation: Early mortality and morbidity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Filipy, R.E.; Lauhala, K.E.; McGee, D.R.; Cannon, W.C.; Buschbom, R.L.; Decker, J.R.; Kuffel, E.G.; Park, J.F.; Ragan, H.A.; Yaniv, S.S.; Scott, B.R.

    1989-05-01

    Rats were given doses of /sup 60/Co gamma radiation and/or lung burdens of /sup 147/Pm (in fused aluminosilicate particles) within lethal ranges in an experiment to determine and compare morbidity and mortality responses for the radiation insults within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Acute mortality and morbidity from inhaled promethium were caused primarily by radiation pneumonitis and pulmonary fibrosis that occurred more than 53 days after exposure. Acute mortality and morbidity from total-body gamma irradiation occurred within 30 days of exposure and resulted from the bone-marrow radiation syndrome. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell levels and by reduced body weight gain in animals that survived the acute gamma radiation syndrome. Inhaled promethium caused a loss of body weight and diminished pulmonary function, but its only effect on blood cell levels was lymphocytopenia. Combined gamma irradiation and promethium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Promethium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the later effect of promethium lung burdens. 70 refs., 68 figs., 21 tabs.

  4. Effects of combined exposure of F344 rats to inhaled Plutonium-239 dioxide and a chemical carcinogen (NNK)

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Carlton, W.W. [Purdue Univ., Lafayette, IN (United States); Griffith, W.C. [and others

    1995-12-01

    Workers in nuclear weapons facilities have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as {sup 239}Pu. Although the carcinogenic effects of inhaled {sup 239}Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to via tobacco smoke is the tobacco-specific nitrosamine 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1(3-pyridyl)-1-butanone (NNK), a product of tobacco curing and the pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent liver, nasal, and pancreatic tumors. From the results presented, it can be concluded that exposure to a chemical carcinogen (NNK) in combination with {alpha}-particle radiation from inhaled {sup 239}PuO{sub 2} acts in, at best, an additive manner in inducing lung cancer in rats.

  5. Effect of Inhaling Cymbopogon martinii Essential Oil and Geraniol on Serum Biochemistry Parameters and Oxidative Stress in Rats

    Directory of Open Access Journals (Sweden)

    Bruna Fernanda Murbach Teles Andrade

    2014-01-01

    Full Text Available The effects of the inhalation of Cymbopogon martinii essential oil (EO and geraniol on Wistar rats were evaluated for biochemical parameters and hepatic oxidative stress. Wistar rats were divided into three groups n=8: G1 was control group, treated with saline solution; G2 received geraniol; and G3 received C. martinii EO by inhalation during 30 days. No significant differences were observed in glycemia and triacylglycerol levels; G2 and G3 decreased P<0.05 total cholesterol level. There were no differences in serum protein, urea, aspartate aminotransferase activity, and total hepatic protein. Creatinine levels increased in G2 but decreased in G3. Alanine aminotransferase activity and lipid hydroperoxide were higher in G2 than in G3. Catalase and superoxide dismutase activities were higher in G3. C. martinii EO and geraniol increased glutathione peroxidase. Oxidative stress caused by geraniol may have triggered some degree of hepatic toxicity, as verified by the increase in serum creatinine and alanine aminotransferase. Therefore, the beneficial effects of EO on oxidative stress can prevent the toxicity in the liver. This proves possible interactions between geraniol and numerous chemical compounds present in C. martinii EO.

  6. Discriminative stimulus properties and brain distribution of phencyclidine in rats following administration by injection and smoke inhalation

    International Nuclear Information System (INIS)

    Wessinger, W.D.; Martin, B.R.; Balster, R.L.

    1985-01-01

    Four male Sprague-Dawley rats were trained to discriminate IP injections of 3.0 mg/kg phencyclidine (PCP) from saline under a 2-lever fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, other doses of injected PCP were tested resulting in dose-dependent increases in PCP-lever selection and dose-dependent decreases in rates of responding. When doses of PCP were administered by exposure to smoke from cigarettes containing PCP, a dose-dependent increase in PCP-lever responding was also observed. delta 9-Tetrahydrocannabinol administered via smoke exposure, up to doses which markedly suppressed response rates, did not result in PCP-appropriate responding, demonstrating the specificity of the PCP stimulus by the inhalation route. Brain levels and distribution of 3 H-PCP were determined in rats administered doses calculated to result in 50% generalization by the IP injection or smoke inhalation routes. By both routes of administration roughly equivalent brain levels were attained and the distribution was relatively even across the seven brain areas analyzed. These results demonstrate the validity of using the injection route of administration when studying PCP experimentally, in spite of the fact that PCP is abused primarily by smoking

  7. Upper respiratory tract nociceptor stimulation and stress response following acute and repeated Cyfluthrin inhalation in normal and pregnant rats: Physiological rat-specific adaptions can easily be misunderstood as adversities.

    Science.gov (United States)

    Pauluhn, Juergen

    2018-01-05

    This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the upper respiratory tract is likely to be perceived as a transient stimulus triggering annoyance and/or avoidance by both rats and humans. However, while thermolabile rats respond to such stresses reflexively, homeothermic humans appear to respond psychologically. With this focus in mind, past inhalation studies in rats and human volunteers were reevaluated and assessed to identify common denominators to such neuroexcitatory stimuli upon inhalation exposure. This analysis supports the conclusion that the adaptive physiological response occurring in rats secondary to such chemosensory stimuli requires inhalation exposures above the chemosensory threshold. Rats, a species known to undergo adaptively a hibernation-like physiological state upon environmental stresses, experienced reflexively-induced bradypnea, bradycardia, hypothermia, and changes in acid-base status during inhalation exposure. After cessation of the sensory stimulus, rapid recovery occurred. Physiological data of male and female rats from a 4-week repeated inhalation study (exposure 6-h/day, 5-times/week) were used to select concentration for a 10-day developmental inhalation toxicity study in pregnant rats. Maternal hypothermia and hypoventilation were identified as likely cause of fetal and placental growth retardations because of a maternal adaptation-driven reduced feto-placental transfer of oxygen. In summary, maternal reflex-hypothermia, reduced cardiac output and placental perfusion, and disruption of the gestation-related hyperventilation are believed to be the maternally mediated causes for developmental

  8. Deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in the lungs of rats with pulmonary emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D L; Damon, E G; Diel, J H; Hahn, F F [Lovelace Foundation for Medical Education and Research, Albuquerque, NM (USA). Inhalation Toxicology Research Inst.

    1981-02-01

    Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in rats.

  9. Retention and translocation of inhaled uranyl nitrate (233U and 232U) in rats

    International Nuclear Information System (INIS)

    Ballou, J.E.; Gies, R.A.; Wogman, N.A.

    1978-01-01

    The uranium-thorium breeder reactors proposed for nuclear power production, and other thorium fuel systems in conventional reactors, utilize fuels and fuel recycle process solutions that have not been evaluated for biological hazard. This project emphasizes studies of the metabolism of the oxide fuels and the nitrate solutions of the major radionuclides, following inhalation, ingestion, or cutaneous application in rodents. Preliminary data are reported for the clearance of inhaled 233 UO 2 (NO 3 ) 2 and 232 UO 2 (NO 3 ) 2 from the lung and their translocation to skeleton

  10. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    Science.gov (United States)

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  11. Neurodevelopmental effects of inhaled vapors of gasoline and ethanol in rats

    Science.gov (United States)

    Gasoline-ethanol blends comprise the major fraction of the fuel used in the US automotive fleet. To address uncertainties regarding the health risks associated with exposure to gasoline with more than 10% ethanol, we are assessing the effects of prenatal exposure to inhaled vapor...

  12. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    Science.gov (United States)

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  13. Gestational Exposure to Inhaled Vapors of Ethanol and Gasoline-Ethanol Blends in Rats

    Science.gov (United States)

    The US automotive fleet is powered primarily by gasoline-ethanol fuel blends containing up to 10% ethanol (ElO). Uncertainties regarding the health risks associated with exposure to ElO prompted assessment of the effects of prenatal exposure to inhaled vapors of gasoline-ethanol ...

  14. Carbon tetrachloride treatment induces anorexia independently of hepatitis in rats.

    Science.gov (United States)

    Okamoto, T; Okabe, S

    2000-08-01

    Oxidative stress is involved in the development of anorexia. In the present study, we examined the possible involvement of anorexia in oxygen radical-induced hepatitis. A low dose of carbon tetrachloride (1 ml/kg of a 1:1 solution with olive oil) was orally administered to rats with and without food restriction. In rats with food restriction, carbon tetrachloride treatment induced hepatitis and reduced the body weight gain. In contrast, carbon tetrachloride treatment did not induce hepatitis in rats without food restriction, but the body weight was decreased. In these rats, the loss of body weight was accompanied by a decrease in food intake. The present results indicate that the administration of a low dose of carbon tetrachloride to rats without food restriction induced anorexia independently of hepatitis.

  15. Investigations of the tracheobronchial epithelium of rat after X-ray irradiation and inhalation of 212Pb aerosol

    International Nuclear Information System (INIS)

    Petri, P.

    1981-01-01

    Early reactions of the tracheobronchial epithelium of rats. Be up to 96 h after irradiation have been investigated. Detection of autoradiographically labelled DNA in the basal cells is a measure of the regenerative function of the epithelium. The labelling index is determined on the basis of histological preparations of trachea and bronchi. Each group of animals was exposed to partial irradiation of the thorax of 500 R, 1000 R and 1500 R. A dose-dependent reduction of the labelling index is found with a minimum after 24 h. A further group of animals inhaled 212 Pb aerosol while the control group was given inactive aerosol. The calculations of Hofmann (1969) yield a value of about 170 rad for the trachea and 480 rad for the upper part of the lungs. The labelling index after 12 h is lower than in the animals exposed to 500 R. It is significantly higher in the lobar bronchi. At the time of sacrificing, the labelling index is higher in all regions than the labelling index of 500 R animals. This labelling method enables quantitative determination of DNA synthesis and labelling index after radiation exposure. The study did not indicate the stage of development in which the so-called ''replacement cells'' of the bronchial epithelium are influenced by radiation exposure. Radionuclide inhalation does not affect the bronchial DNA synthesis index as strongly as assumed on the basis of dose estimates. Ater 12 h, the trachea shows a stronger reaction than the bronchi. Explanations are offered. (orig./MG) [de

  16. Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

    OpenAIRE

    White, Kimber L.; DeLorme, Michael P.; Beatty, Patrick W.; Smith, Matthew J.; Peachee, Vanessa L.

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (...

  17. Impact of gasoline inhalation on some neurobehavioural characteristics of male rats

    OpenAIRE

    Kinawy Amal A

    2009-01-01

    Abstract Background This paper examines closely and compares the potential hazards of inhalation of two types of gasoline (car fuel). The first type is the commonly use leaded gasoline and the second is the unleaded type enriched with oxygenate additives as lead substituent in order to raise the octane number. The impacts of gasoline exposure on Na+, K+-ATPase, superoxide dismutase (SOD), acetylcholinesterase (AChE), total protein, reduced glutathione (GSH), and lipid peroxidation (TBARS) in ...

  18. Genotoxicity of Silver Nanoparticles in Lung Cells of Sprague Dawley Rats after 12 Weeks of Inhalation Exposure

    Directory of Open Access Journals (Sweden)

    Hyun Sun Cho

    2013-11-01

    Full Text Available Due to the widespread use of silver nanoparticles in consumer products, the toxicity of silver nanoparticles has also been studied in relation to their application. However, most genotoxicity studies of silver nanoparticles have been performed in vitro. Therefore, this study evaluated the DNA damage to lung cells caused by repeated inhalation of silver nanoparticles. Male Sprague Dawley rats were exposed to silver nanoparticles for 12 weeks in a whole-body inhalation chamber. The animals were divided into one control group and three dose groups that were exposed to silver nanoparticles (14–15 nm diameter at concentrations of 0.66 × 106 particles/cm3 (49 μg/m3, low dose, 1.41 × 106 particles/cm3 (117 μg/m3, middle dose, and 3.24 × 106 particles /cm3 (381 μg/m3, high dose, respectively, for six hours/day over 12 weeks. The rats were sacrificed after the 12-week exposure period and the DNA damage assessed using a Comet assay of cells obtained from the right lungs. The olive tail moment values were 2.93 ± 0.19, 3.81 ± 0.23, 3.40 ± 0.22, and 5.16 ± 0.32 for the control, low-, middle-, and high-dose groups, respectively. Although no dose-dependent results were observed, a significant increase in the level of DNA damage was noted for the high-dose group.

  19. Ototoxic potential of JP-8 and a Fischer-Tropsch synthetic jet fuel following subacute inhalation exposure in rats.

    Science.gov (United States)

    Fechter, Laurence D; Gearhart, Caroline A; Fulton, Sherry

    2010-07-01

    This study was undertaken to identify the ototoxic potential of two jet fuels presented alone and in combination with noise. Rats were exposed via a subacute inhalation paradigm to JP-8 jet fuel, a kerosene-based fuel refined from petroleum, and a synthetic fuel produced by the Fischer-Tropsch (FT) process. Although JP-8 contains small ( approximately 5%) concentrations of aromatic hydrocarbons some of which known to be ototoxic, the synthetic fuel does not. The objectives of this study were to identify a lowest observed adverse effect level and a no observed adverse effect level for each jet fuel and to provide some preliminary, but admittedly, indirect evidence concerning the possible role of the aromatic hydrocarbon component of petroleum-based jet fuel on hearing. Rats (n = 5-19) received inhalation exposure to JP-8 or to FT fuel for 4 h/day on five consecutive days at doses of 500, 1000, and 2000 mg/m(3). Additional groups were exposed to various fuel concentrations followed by 1 h of an octave band of noise, noise alone, or no exposure to fuel or noise. Significant dose-related impairment in the distortion product otoacoustic emissions (DPOAE) was seen in subjects exposed to combined JP-8 plus noise exposure when JP-8 levels of at least 1000 mg/m(3) were presented. No noticeable impairment was observed at JP-8 levels of 500 mg/m(3) + noise. In contrast to the effects of JP-8 on noise-induced hearing loss, FT exposure had no effect by itself or in combination with noise exposure even at the highest exposure level tested. Despite an observed loss in DPOAE amplitude seen only when JP-8 and noise were combined, there was no loss in auditory threshold or increase in hair cell loss in any exposure group.

  20. Metabolites from inhalation of aerosolized S-8 synthetic jet fuel in rats.

    Science.gov (United States)

    Tremblay, Raphael T; Martin, Sheppard A; Fisher, Jeffrey W

    2011-01-01

    Alternative fuels are being considered for civilian and military uses. One of these is S-8, a replacement jet fuel synthesized using the Fischer-Tropsch process, which contains no aromatic compounds and is mainly composed of straight and branched alkanes. Metabolites of S-8 fuel in laboratory animals have not been identified. The goal of this study was to identify metabolic products from exposure to aerosolized S-8 and a designed straight-chain alkane/polyaromatic mixture (decane, undecane, dodecane, tridecane, tetradecane, pentadecane, naphthalene, and 2-methylnaphthalene) in male Fischer 344 rats. Collected blood and tissue samples were analyzed for 70 straight and branched alcohols and ketones ranging from 7 to 15 carbons. No fuel metabolites were observed in the blood, lungs, brain, and fat following S-8 exposure. Metabolites were detected in the liver, urine, and feces. Most of the metabolites were 2- and 3-position alcohols and ketones of prominent hydrocarbons with very few 1- or 4-position metabolites. Following exposure to the alkane mixture, metabolites were observed in the blood, liver, and lungs. Interestingly, heavy metabolites (3-tridecanone, 2-tridecanol, and 2-tetradecanol) were observed only in the lung tissues possibly indicating that metabolism occurred in the lungs. With the exception of these heavy metabolites, the metabolic profiles observed in this study are consistent with previous studies reporting on the metabolism of individual alkanes. Further work is needed to determine the potential metabolic interactions of parent, primary, and secondary metabolites and identify more polar metabolites. Some metabolites may have potential use as biomarkers of exposure to fuels.

  1. Discovery of unique and ENM— specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kreyling, Wolfgang G., E-mail: kreyling@helmholtz-muenchen.de

    2016-05-15

    The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood-brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24 h after a 1-hour aerosol inhalation of 20 nm-sized, {sup 192}Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a + b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24 h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both – URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure. - Highlights: • Nanoparticle (NP) translocation from nose versus lungs to brain is differentiated. • Differential exposure of 20 nm radio-NP:nose-only versus intratracheal inhalation • The nose-brain path precedes via nerves, the lungs

  2. Bronchoalveolar permeability changes in rats inhaling gas/particle combinations during rest or exercise

    International Nuclear Information System (INIS)

    Bhalla, D.K.; Phalen, R.F.; Mannix, R.C.; Lavan, S.M.; Crocker, T.T.

    1986-01-01

    Bronchoalveolar (BA) injury in rats exposed at rest or exercise to air pollutants was studied by changes in epithelial permeability. Rats exposed to air, single gases or pollutant combinations were anesthetized, tracheostomized, and placed on an incline. /sup 99m/Tc-DTPA was delivered directly to a major bronchus. Radioactivity measurements were made on blood samples collected during first 10 min. Exposure of resting rats to 0.6 ppm O 3 increased BA permeability just after exposure, but it was normal 24 hrs later; in exercising rats the increase was greater than in rats exposed at rest, and it persisted up to 24 hrs. NO 2 at 6 ppm did not affect permeability. Exposure of resting rats to 2.5 ppm NO 2 + 0.6 ppm O 3 only increased permeability right after the exposure, but in exercising rats this exposure resulted in a greater permeability which remained elevated up to 24 hrs. Exposure of exercising rats to 0.8 ppm O 3 + 10 ppm HCHO increased permeability. Exposure of resting rats to an atmosphere of 0.6 ppm O 3 + 2.5 ppm NO 2 + 5 ppm SO 2 + 1 mg/m 3 sulfates of ferric, ammonium and manganese also produced an increase in permeability that persisted up to 24 hrs. The results suggest potentiation of the pollutant effects by exercise, but there is no indication of synergistic effect of pollutant combinations on BA permeability

  3. Part 1. Assessment of carcinogenicity and biologic responses in rats after lifetime inhalation of new-technology diesel exhaust in the ACES bioassay.

    Science.gov (United States)

    McDonald, Jacob D; Doyle-Eisele, Melanie; Seagrave, JeanClare; Gigliotti, Andrew P; Chow, Judith; Zielinska, Barbara; Mauderly, Joe L; Seilkop, Steven K; Miller, Rodney A

    2015-01-01

    component of TDE was considered the primary driver of lung tumorigenesis in rats exposed chronically to historical diesel emissions. Emissions from a 2007-compliant, 500-horsepower-class engine and after treatment system operated on a variable-duty cycle were used to generate the animal inhalation test atmospheres. Four groups were exposed to one of three concentrations (dilutions) of exhaust combined with crankcase emissions, or to clean air as a negative control. Dilutions of exhaust were set to yield average integrated concentrations of 4.2, 0.8, and 0.1 ppm nitrogen dioxide (NO2). Exposure atmospheres were analyzed by daily measurements of key effects of NTDE in the present study were generally consistent with those observed previously in rats exposed chronically to NO2 alone. This suggests that NO2 may have been the primary driver of the biologic responses to NTDE in the present study. There was little evidence of effects characteristic of rats exposed chronically to high concentrations of DPM in TDE, such as an extensive accumulation of DPM within alveolar macrophages and inflammation leading to neoplastic transformation of epithelia and lung tumors. components and periodic detailed physical-chemical characterizations. Exposures were conducted 16 hours/day (overnight, during the rats' most active period), 5 days/week. Responses to exposure were evaluated via hematology, serum chemistry, bronchoalveolar lavage (BAL), lung cell proliferation, histopathology, and pulmonary function. The exposures were accomplished as planned, with average integrated exposure concentrations within 20% of the target dilutions. The major components from exhaust were the gaseous inorganic compounds, nitrogen monoxide (NO), NO2, and carbon monoxide (CO). Minor components included low concentrations of DPM and volatile and semi-volatile organic compounds (VOCs and SVOCs). Among the more than 100 biologic response variables evaluated, the majority showed no significant difference from control

  4. Late effects following inhalation of mixed oxide (U,PuO2) mox aerosol in the rat

    International Nuclear Information System (INIS)

    Griffiths, N.; Van Der Meeren, A.; Fritsch, P.; Maximilien, R.

    2008-01-01

    Exposure to alpha-emitting particles is a potential long-term health risk to workers in nuclear fuel fabrication plants. Mixed Oxide (MOX: U,PuO 2 ) fuels containing low percentages of plutonium obtained from spent nuclear fuels are increasingly employed and in the case of accidental contamination by inhalation or wounds may result in the development of late-occurring pathologies such as lung cancer. However the long term risks particularly with regard to lung cancer are to date unclear. In the case of MOX the risk may indeed be different from that assigned to the individual components, plutonium and uranium. Several factors are influential (i) the dissolution of Pu depends on the physico-chemical properties, for example risk of lung cancer is increased 10 fold after Pu(NO 3 ) 2 as compared with PuO 2 . (ii) The solubility of Pu is variable whether delivered as PuO 2 or contained within MOX. (iii) The risk of cancer appears to increase with spatial homogeneity of the lung alpha dose. The objective of this study was to investigate the long term effects in rat lungs following MOX aerosol inhalation of similar particle size containing 2.5 or 7.1% Pu. Conscious rats were exposed to MOX aerosols using a 'nose-only' system and kept for their entire life (2-3 years). Different Initial Lung Deposits (ILDs) were obtained using different concentrations of the MOX suspension. Lung total alpha activity was determined in vivo at intervals over the study period by external counting as well as at autopsy in order to estimate the total lung dose. Anatomo-pathological and immunohistochemical analyses were performed on fixed lung tissue after euthanasia. The frequencies of lung pathologies and tumours were determined on lung sections at several different levels. In addition, autoradiography of lung sections was performed in order to assess the spatial localisation of a activity. Inhalation of MOX at ILD ranging from 1-20 kBq resulted in lung pathologies (90% of exposed rats

  5. Inhaled Steroids

    Science.gov (United States)

    ... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

  6. Inhalant Abuse

    Science.gov (United States)

    ... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

  7. The protective effect of propolis on damage to lung and blood in rats by inhaled radioactive radon and its progeny

    International Nuclear Information System (INIS)

    Ding Jiansong; Nie Jihua; Tong Jian

    2006-01-01

    Twenty-eight male wistar rats were randomly divided into seven groups, i.e. the radon groups (3), the propolis+radon groups (3) and the control (1). The propolis+radon groups were fed intragastrically with propolis 0.2 g/kg, before exposing them, together with the radon groups, to radon and its progeny with the cumulative dose up to 30, 67 and 111 working level month (WLM), respectively. The levels of SOD (superoxide dismutase) and MDA (Malonic dialdehyde) in blood and lung tissue were determined. The SOD level of in blood and lung tissues of the radon groups decreased significantly and the MDA level increased. The MDA level in lung tissue of the 30 WLM propolis+radon group was significantly higher than the 30 WLM radon group. The SOD level in lung tissue of the 67 WLM propolis+radon group was significantly higher, but the MDA level was significantly lower, than the 67 WLM radon group. Both the SOD and MDA levels in blood and lung tissue of the 111 WLM propolis+radon group were significantly higher than the 111 WLM radon group. In conclusion, the inhalation of radon and its progeny can lead to persistent disturbance of the redox state in rats. Propolis show some protective effects on the redox damage under the experimental conditions. (authors)

  8. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

    Science.gov (United States)

    Cui, Jin; Chen, Xiao; Zhai, Xiao; Shi, Dongchen; Zhang, Rongjia; Zhi, Xin; Li, Xiaoqun; Gu, Zhengrong; Cao, Liehu; Weng, Weizong; Zhang, Jun; Wang, Liping; Sun, Xuejun; Ji, Fang; Hou, Jiong; Su, Jiacan

    2016-10-29

    Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically. Copyright © 2016. Published by Elsevier Ltd.

  9. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set is an Excel file pertaining to the study that examined nasal, pulmonary, and systemic effects of acrolein in rats acutely exposed to a range of...

  10. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring

    Science.gov (United States)

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  11. Effects of combined inhalation exposure of rats to 239PuO2 and beryllium metal

    International Nuclear Information System (INIS)

    Finch, G.L.; Mewhinney, J.A.; Hoover, M.D.; Haley, P.J.; Cuddihy, R.G.; Griffith, W.C.; Boecker, B.B.

    1988-01-01

    We exposed rats acutely to achieve one of two initial lung burdens (ILBs) of 239 PuO 2 alone or in combination with one of three ILBs of beryllium metal. Additional control groups of rats were sham exposed to air. Currently, approximately 58% of all rats planned for inclusion have been exposed. This report describes procedures used for the exposure, maintenance, and evaluation of rats in this study. Most of the animals are to be held for their life span in order to quantitate cancer incidence, with other animals assigned to serial sacrifice groups for quantitation of Pu and Be retention and determination of translocation patterns. Exposure to beryllium at any of the three doses tested retarded clearance of plutonium from the lung by a factor of approximately six. Acute inflammatory responses were studied in a separate group of rats exposed to Be. Except for rats receiving the highest ILB of beryllium metal, no differences between exposed and sham-exposed control groups have yet been noted in terms of mortality, weight changes, and clinical signs. (author)

  12. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

    Science.gov (United States)

    Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

    2017-06-20

    The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm 2 per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm 2 ; accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m 2 /g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

  13. Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks

    International Nuclear Information System (INIS)

    Morgan, Daniel L.; Little, Peter B.; Herr, David W.; Moser, Virginia C.; Collins, Bradley; Herbert, Ronald; Johnson, G. Allan; Maronpot, Robert R.; Harry, G. Jean; Sills, Robert C.

    2004-01-01

    Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N 3 , P 4 , N 4 , and N 5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree

  14. Development of a physiologically based pharmacokinetic model for inhalation of jet fuels in the rat.

    Science.gov (United States)

    Martin, Sheppard A; Campbell, Jerry L; Tremblay, Raphael T; Fisher, Jeffrey W

    2012-01-01

    The pharmacokinetic behavior of the majority of jet fuel constituents has not been previously described in the framework of a physiologically based pharmacokinetic (PBPK) model for inhalation exposure. Toxic effects have been reported in multiple organ systems, though exposure methods varied across studies, utilizing either vaporized or aerosolized fuels. The purpose of this work was to assess the pharmacokinetics of aerosolized and vaporized fuels, and develop a PBPK model capable of describing both types of exposures. To support model development, n-tetradecane and n-octane exposures were conducted at 89 mg/m(3) aerosol+vapor and 1000-5000 ppm vapor, respectively. Exposures to JP-8 and S-8 were conducted at ~900-1000 mg/m(3), and ~200 mg/m(3) to a 50:50 blend of both fuels. Sub-models were developed to assess the behavior of representative constituents and grouped unquantified constituents, termed "lumps", accounting for the remaining fuel mass. The sub-models were combined into the first PBPK model for petroleum and synthetic jet fuels. Inhalation of hydrocarbon vapors was described with simple gas-exchange assumptions for uptake and exhalation. For aerosol droplets systemic uptake occurred in the thoracic region. Visceral tissues were described using perfusion and diffusion-limited equations. The model described kinetics at multiple fuel concentrations, utilizing a chemical "lumping" strategy to estimate parameters for fractions of speciated and unspeciated hydrocarbons and gauge metabolic interactions. The model more accurately simulated aromatic and lower molecular weight (MW) n-alkanes than some higher MW chemicals. Metabolic interactions were more pronounced at high (~2700-1000 mg/m(3)) concentrations. This research represents the most detailed assessment of fuel pharmacokinetics to date.

  15. Lung response to ultrafine Kevlar aramid synthetic fibrils following 2-year inhalation exposure in rats.

    Science.gov (United States)

    Lee, K P; Kelly, D P; O'Neal, F O; Stadler, J C; Kennedy, G L

    1988-07-01

    Four groups of 100 male and 100 female rats were exposed to ultrafine Kevlar fibrils at concentrations of 0, 2.5, 25, and 100 fibrils/cc for 6 hr/day, 5 days/week for 2 years. One group was exposed to 400 fibrils/cc for 1 year and allowed to recover for 1 year. At 2.5 fibrils/cc, the lungs had normal alveolar architecture with a few dust-laden macrophages (dust cell response) in the alveolar airspaces. At 25 fibrils/cc, the lungs showed a dust cell response, slight Type II pneumocyte hyperplasia, alveolar bronchiolarization, and a negligible amount of collagenized fibrosis in the alveolar duct region. At 100 fibrils/cc, the same pulmonary responses were seen as at 25 fibrils/cc. In addition, cystic keratinizing squamous cell carcinoma (CKSCC) was found in 4 female rats, but not in male rats. Female rats had more prominent foamy alveolar macrophages, cholesterol granulomas, and alveolar bronchiolarization. These pulmonary lesions were related to the development of CKSCC. The lung tumors were derived from metaplastic squamous cells in areas of alveolar bronchiolarization. At 400 fibrils/cc following 1 year of recovery, the lung dust content, average fiber length, and the pulmonary lesions were markedly reduced, but slight centriacinar emphysema and minimal collagenized fibrosis were found in the alveolar duct region. One male and 6 female rats developed CKSCC. The lung tumors were a unique type of experimentally induced tumors in the rats and have not been seen as spontaneous tumors in man or animals. Therefore, the relevance of this type of lung tumor to the human situation is minimal.

  16. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

  17. Comparative evaluation of nose-only vs. whole-body inhalation exposures for rats

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, H C; Snipes, M B; Eidson, A F; Hobbs, C H

    1988-12-01

    Two types of rat exposure chambers, nose-only and whole-body chambers, were evaluated simultaneously for the temporal and spatial distribution of the same test aerosols within the chambers, both with and without animals present. Results indicated that both types of exposure chambers performed well, with coefficients of variation less than 10% for both temporal and spatial variations. (author)0.

  18. Comparative evaluation of nose-only vs. whole-body inhalation exposures for rats

    International Nuclear Information System (INIS)

    Yeh, H.C.; Snipes, M.B.; Eidson, A.F.; Hobbs, C.H.

    1988-01-01

    Two types of rat exposure chambers, nose-only and whole-body chambers, were evaluated simultaneously for the temporal and spatial distribution of the same test aerosols within the chambers, both with and without animals present. Results indicated that both types of exposure chambers performed well, with coefficients of variation less than 10% for both temporal and spatial variations. (author)

  19. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-11-01

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  20. Lung tumors and radon inhalation in over 2000 rats: Approximate linearity across a wide range of doses and potentiation by tobacco smoke

    International Nuclear Information System (INIS)

    Gray, R.G.; Lafuma, J.; Parish, S.E.; Peto, R.; CEA Centre d'Etudes Nucleaires de Fontenay-aux-Roses

    1986-01-01

    More than 2000 rats were exposed to cumulative doses of up to 28,000 WLMs of radon gas. More than 300 pulmonary tumors were induced by this exposure, most being nonfatal lesions detected only at autopsy of animals that had died of unrelated causes. Above 6000 WLMs rats suffered increasingly from life shortening due to radiation-induced nonneoplastic causes and so had less time in which to develop tumors. When adjusted for these competing causes of death, the hazard function for the excess risk of developing pulmonary tumors was approximately linearly related to dose throughout the range of doses studied. This suggests that some previously reported high-dose ''reductions'' in radiogenic tumor-induction rates may chiefly have involved the killing of rats rather than the killing of precursor cells. Rats exposed to radon and then to six months of inhalation of tobacco smoke had a four times greater age-specific prevalence of pulmonary tumors than rats exposed to an identical radon dose either alone or preceded by tobacco smoke inhalation. This suggests that tobacco smoke may accelerate the carcinogenic process by acting as a promoter of radiation-induced somatic damage. These data suggest that, for assessing human risk from exposure to radon, the linear model should be assumed, but that the WLM is not on its own an adequate index of carcinogenic insult. 7 refs., 2 figs., 4 tabs

  1. The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

    Science.gov (United States)

    Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

    2017-02-01

    The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    International Nuclear Information System (INIS)

    Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

    2013-01-01

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  3. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Turowska, Agnieszka [sterna biologicals GmbH and Co. KG, Marburg (Germany); Librizzi, Damiano [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Baumgartl, Nadja [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Kuhlmann, Jens; Dicke, Tanja [sterna biologicals GmbH and Co. KG, Marburg (Germany); Merkel, Olivia [Department of Pharmaceutical Sciences, Wayne State University, Detroit (United States); Homburg, Ursula [sterna biologicals GmbH and Co. KG, Marburg (Germany); Höffken, Helmut [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Renz, Harald [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Garn, Holger, E-mail: garn@staff.uni-marburg.de [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany)

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  4. Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

    Science.gov (United States)

    Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

    2017-12-11

    Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

  5. Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure

    International Nuclear Information System (INIS)

    Chang, Sue; Mader, Brian T.; Lindstrom, Kent R.; Lange, Cleston C.; Hart, Jill A.; Kestner, Thomas A.; Schulz, Jay F.; Ehresman, David J.; Butenhoff, John L.

    2017-01-01

    Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6 h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24 h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8−14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes. - Highlights: • First inhalation study reported in rats that investigates the conversion of a major precursor compound (EtFOSE) to form PFOS. • Systemic

  6. Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sue, E-mail: s.chang@mmm.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Mader, Brian T., E-mail: bmader@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Lindstrom, Kent R., E-mail: krlindstrom@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Lange, Cleston C., E-mail: clange@mmm.com [Environmental Laboratory, 3M Company, St. Paul, MN 55144 (United States); Hart, Jill A., E-mail: jahart@mmm.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Kestner, Thomas A., E-mail: takestner@mmm.com [Materials Resource Division, 3M Company, St. Paul, MN 55144 (United States); Schulz, Jay F., E-mail: jfschulz@mmm.com [Materials Resource Division, 3M Company, St. Paul, MN 55144 (United States); Ehresman, David J., E-mail: depqehr@gmail.com [Medical Department, 3M Company, St. Paul, MN 55144 (United States); Butenhoff, John L., E-mail: john.butenhoff@gmail.com [SaluTox, LLC, Lake Elmo, MN 55042 (United States)

    2017-05-15

    Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6 h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24 h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8−14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes. - Highlights: • First inhalation study reported in rats that investigates the conversion of a major precursor compound (EtFOSE) to form PFOS. • Systemic

  7. Teratogenicity following inhalation exposure of rats to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Poston, K.A.; Mahlum, D.D.; Sikov, M.R.

    1982-01-01

    On days 12 to 16 of gestation pregnant rats were exposed to heavy distillate (hd), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1/sup -1/ (1.8 ..mu..m, mass medium aerodynamic diameter); groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1/sup -1/) were largely unaffected. Embryolethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.

  8. Teratogenicity following inhalation exposure of rats to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Poston, K.A.; Mahlum, D.D.; Sikov, M.R.

    1982-01-01

    On days 12-16 of gestation pregnant rats were exposed to heavy distillate (HD), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1/sup -1/ (1.8 ..mu..m, mass medium aerodynamic diameter (MMAD)); groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1/sup -1/) were largely unaffected. Embryolethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.

  9. Histogenesis of lung tumors induced in rats by inhalation of α emitters. An overview

    International Nuclear Information System (INIS)

    Masse, R.

    1979-01-01

    Recent reviews have shown that simular risks coefficients for α irradiation of the lung in man could be deduced using epidemiological or experimental data in animals. Most experimental data were obtained in rats. In this overview the histogenesis and ultrastructure of lung tumors are presented. Only few tumors originating from lung parenchyma could be considered as non relevant for extrapolation to man. Most tumors arose from axial bronchus or bronchioles and their histogenesis was very similar to what is known in man. The only striking difference between the two species was related to the growth characteristics of the tumors. Tumors in rat, frequently papillary, acquired only slowly their full malignancy. They seem to be only potentially malignant. Two main types of tumors were considered: bronchogenic (B) and bronchiolo alveolar (b.a.) carcinomas. Survivals of the cancerous rats were log normal distribution in a given group of dose and were supposed to reflect latent period. No difference was found between B and b.a. carcinomas; geometric standard deviation did not increase when doses decrease. Since risk coefficients were found to increase when dose decreased, and through latent period fitted well with a power function of dose within the dose range studied, it is observed that the latent period can not be deduced by extrapolation at low doses. b.a. carcinomas prevailed at low doses; the relevance of this observation to man is however dubious since combined action with environmental carcinogens led to a high prevalence of B. carcinomas. Though genetic and immune surveillance are factors of some importance in the determination of the tumors it is suggested that critical individuals will be mostly multi-exposed individuals

  10. Acute and Two-Week Inhalation Toxicity Studies in Rats for Polyalphaolefin (PAO) Fluid

    Science.gov (United States)

    2017-04-01

    Institute for Science and Education (ORISE)); Antonio Brown (ORISE); Joseph B. Brune (Level One Personnel); Kathy A. Frondorf, Nathan M. Gargas... Nutrition , International, LLC, Brentwood MO) and reverse osmosis purified municipal tap water, ad libitum. Rats were randomly assigned to exposure...0.00 Red blood cells (# x 106/µL) 9.08 0.69 8.82 0.83 8.86 0.52 9.01 0.44 Hemoglobin (g/dL) 15.08 1.29 14.70 1.65 14.87 1.16 15.06 0.78 Hematocrit

  11. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    Directory of Open Access Journals (Sweden)

    Akamatsu Akinori

    2012-02-01

    Full Text Available Abstract Background Chlorine dioxide (CD gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human.

  12. Effects of subchronic inhalation exposure of rats to emissions from a diesel engine burning soybean oil-derived biodiesel fuel.

    Science.gov (United States)

    Finch, G L; Hobbs, C H; Blair, L F; Barr, E B; Hahn, F F; Jaramillo, R J; Kubatko, J E; March, T H; White, R K; Krone, J R; Ménache, M G; Nikula, K J; Mauderly, J L; Van Gerpen, J; Merceica, M D; Zielinska, B; Stankowski, L; Burling, K; Howell, S

    2002-10-01

    There is increasing interest in diesel fuels derived from plant oils or animal fats ("biodiesel"), but little information on the toxicity of biodiesel emissions other than bacterial mutagenicity. F344 rats were exposed by inhalation 6 h/day, 5 days/wk for 13 wk to 1 of 3 dilutions of emissions from a diesel engine burning 100% soybean oil-derived fuel, or to clean air as controls. Whole emissions were diluted to nominal NO(x) concentrations of 5, 25, or 50 ppm, corresponding to approximately 0.04, 0.2, and 0.5 mg particles/m(3), respectively. Biologically significant, exposure-related effects were limited to the lung, were greater in females than in males, and were observed primarily at the highest exposure level. There was a dose-related increase in the numbers of alveolar macrophages and the numbers of particles in the macrophages, as expected from repeated exposure, but no neutrophil response even at the highest exposure level. The macrophage response was reduced 28 days after cessation of the exposure. Among the high-level females, the group mean lung weight/body weight ratio was increased, and minimal, multifocal bronchiolar metaplasia of alveolar ducts was observed in 4 of 30 rats. Lung weights were not significantly increased, and metaplasia of the alveolar ducts was not observed in males. An increase in particle-laden macrophages was the only exposure-related finding in lungs at the intermediate and low levels, with fewer macrophages and fewer particles per macrophage at the low level. Alveolar histiocytosis was observed in a few rats in both exposed and control groups. There were statistically significant, but minor and not consistently exposure-related, differences in body weight, nonpulmonary organ weights, serum chemistry, and glial fibrillary acidic protein in the brain. There were no significant exposure-related effects on survival, clinical signs, feed consumption, ocular toxicity, hematology, neurohistology, micronuclei in bone marrow, sister

  13. Inhaled tobacco sterols: uptake by the lungs and disposition to selected organs of rats

    International Nuclear Information System (INIS)

    Holden, W.E.; Maier, J.M.; Liebler, J.M.; Malinow, M.R.

    1988-01-01

    Tobacco sterols (cholesterol, beta-sitosterol, campesterol, and stigmasterol) are present in tobacco smoke and appear in plasma of mammals exposed to cigarette smoke. Because tobacco sterols may be important in the pathogenesis of smoking-induced lung and vascular diseases, we studied the pattern of deposition of cigarette sterols in the lungs and appearance of cigarette sterols in plasma and body organs of rats. After exposure to twenty 5 ml puffs of smoke from tobacco labeled with [4- 14 C]cholesterol or beta-[4- 14 C]sitosterol, rats were killed just after exposure (day 0) and on days 2, 5, 8, 11, 15, and 30, and the lungs and selected body organs analyzed for activity. We found that cigarette sterols are associated with particulates in cigarette smoke, deposited mostly in distal airspaces and parenchyma of the lungs, and appear in plasma and several body organs for more than 30 days after this single exposure to cigarette smoke. Bronchoalveolar lavage fluid contained relatively small amounts of radiolabel for only the first few days, suggesting that most of the sterols were rapidly incorporated in lung parenchyma. Because disorders of sterol metabolism have been implicated in a variety of diseases including atherosclerosis and cancer, the significance of tobacco sterols to human smoking-induced diseases deserves further study

  14. Anxiolytic effects of lavender oil inhalation on open-field behaviour in rats.

    Science.gov (United States)

    Shaw, D; Annett, J M; Doherty, B; Leslie, J C

    2007-09-01

    To establish a valid animal model of the effects of olfactory stimuli on anxiety, a series of experiments was conducted using rats in an open-field test. Throughout, effects of lavender oil were compared with the effects of chlordiazepoxide (CDP), as a reference anxiolytic with well-known effects on open-field behaviour. Rats were exposed to lavender oil (0.1-1.0 ml) for 30 min (Experiment 1) or 1h (Experiment 2) prior to open-field test and in the open field or injected with CDP (10 mg/kg i.p.). CDP had predicted effects on behaviour, and the higher doses of lavender oil had some effects on behaviour similar to those of CDP. In Experiment 3, various combinations of pre-exposure times and amounts of lavender oil were used. With sufficient exposure time and quantity of lavender the same effects were obtained as in Experiment 2. Experiment 4 demonstrated that these behavioural effects of lavender could be obtained following pre-exposure, even if no oil was present in the open-field test. In Experiments 2-4, lavender oil increased immobility. Together, these experiments suggest that lavender oil does have anxiolytic effects in the open field, but that a sedative effect can also occur at the highest doses.

  15. Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

    International Nuclear Information System (INIS)

    Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

    2015-01-01

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O 3 ) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O 3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O 3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O 3 , 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O 3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O 3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O 3 . In conclusion, short-term O 3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia, hyperglycemia, and glucose intolerance

  16. Studies on the Inhalation Toxicity of Dyes Present in Colored Smoke Munitions. Phase IV. 90-Day Inhalation Exposures of Rats to Dye Aerosols

    Science.gov (United States)

    1985-10-01

    virus , rat corona - virus /Sialodacryodenitis virus (RCV/SOAV), Ir Reovirus type 3 (Reo 3), Theiler’s encephalomyelitis virus (GD VII), Toolan’s H-I virus (H...1), Kilham rat virus (KRV). Lymphocytic choriomeningitis (LCM) and Mvcoplasma pulmonis. Bacterial cultures are also performed on swabs or tissue... Cats _____ ___ -.--oci of Mononuclear Cells11 .:._Lubular Mineral ization 12221122 33 -LUNG __ __ SHemorrhage Pipment Deposition ::Hyperplasia of

  17. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats.

    Science.gov (United States)

    Perez, Christina M; Hazari, Mehdi S; Ledbetter, Allen D; Haykal-Coates, Najwa; Carll, Alex P; Cascio, Wayne E; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2015-01-01

    Air pollution exposure affects autonomic function, heart rate, blood pressure and left ventricular function. While the mechanism for these effects is uncertain, several studies have reported that air pollution exposure modifies activity of the carotid body, the major organ that senses changes in arterial oxygen and carbon dioxide levels, and elicits downstream changes in autonomic control and cardiac function. We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke and diesel exhaust, would activate the carotid body chemoreceptor response and lead to secondary cardiovascular responses in rats. Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein gas or filtered air in whole body plethysmograph chambers. To determine if the carotid body mediated acrolein-induced cardiovascular responses, rats were pretreated with an inhibitor of cystathionine γ-lyase (CSE), an enzyme essential for carotid body signal transduction. Acrolein exposure induced several cardiovascular effects. Systolic, diastolic and mean arterial blood pressure increased during exposure, while cardiac contractility decreased 1 day after exposure. The cardiovascular effects were associated with decreases in pO2, breathing frequency and expiratory time, and increases in sympathetic tone during exposure followed by parasympathetic dominance after exposure. The CSE inhibitor prevented the cardiovascular effects of acrolein exposure. Pretreatment with the CSE inhibitor prevented the cardiovascular effects of acrolein, suggesting that the cardiovascular responses with acrolein may be mediated by carotid body-triggered changes in autonomic tone. (This abstract does not reflect EPA policy.).

  18. Inhalation toxicology of diesel fuel obscurant aerosol in Sprague-Dawley rats. Final report, Phase 3, subchronic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lock, S.; Dalbey, W.; Schmoyer, R.; Griesemer, R.

    1984-12-01

    Inhalation exposures were performed twice per week, for 13 weeks, to determine whether there was any potential toxicity to rats of comparatively low concentrations of a condensation aerosol from diesel fuel. Changes in breathing frequency and the response of animals to a loud sharp sound (startle response) were measured in selected animals prior to the start of the exposures, at various time points during the thirteen week exposure period, and at monthly intervals during the recovery period. Assays were performed on selected animals at the end of the exposure period, and again after the two month recovery period. Endpoints included pulmonary function tests, numbers of alveolar free cells, clinical chemistry, hematology, organ weights and histopathology. No mortalities were recorded during the exposure or recovery periods. Slight toxicity occurred at these low aerosol concentrations with the loss in body weight of all treated animals during the exposure period. During the exposure period there were also some slight changes in startle reflex, however, these were apparently acute effects, and there appeared to be no permanent CNS involvement as measured by this endpoint. Immediately post-exposure, the numbers of lavaged alveolar macrophages were slightly elevated in all aerosol exposed animals. Pulmonary function tests, pulmonary gas exchange and dynamic lung tests were all apparently unaffected by these low diesel fuel aerosol exposures. Changes in tissue weights in aerosol exposed animals were minor and the few histopathological lesions were randomly scattered amongst all groups included in this study and were more attributable to the age of the animals than any specific treatment group. No significant cumulative toxicity may be attributed to these diesel fuel aerosol exposures. 14 references, 1 figure, 42 tables.

  19. Cigarette smoke inhalation increases the alveolar bone loss caused by primary occlusal trauma in a rat model.

    Science.gov (United States)

    Campos, M L G; Corrêa, M G; Júnior, F H N; Casati, M Z; Sallum, E A; Sallum, A W

    2014-04-01

    Occlusal trauma (OT) and smoking are both factors that alter alveolar bone metabolism and therefore could synergistically act on alveolar bone loss. The aim of this experimental study was to evaluate the influence of short-term cigarette smoke inhalation (CSI) on inter-radicular alveolar bone loss promoted by primary OT in a rat model. Forty-eight animals were randomly assigned to one of three groups based on treatment type: OT + CSI (n = 16), animals were exposed to CSI three times per day, for 8 min per exposure, and they concomitantly received unilateral vertical augmentation creating an occlusal interference inducing experimental OT; OT (n = 16), animals received only unilateral vertical augmentation; negative control (NC; n = 16), animals maintained for equal periods to achieve periodontal baseline values of periodontal ligament dimension. Each group was divided into two subgroups (n = 8) based on treatment length: 7 or 14 d. After 7 d, the OT + CSI group exhibited significantly higher bone loss compared to the NC group (p = 0.0022). After 14 d, the OT (p < 0.0001) and OT + CSI (p < 0.0001) groups presented significantly higher bone loss compared to the NC group, and OT + CSI resulted in significantly higher bone loss than OT alone (p = 0.0241). The number of tartrate-resistant acid phosphatase-positive cells on the linear surface of the bone crest after 7 d was significantly higher in the OT + CSI group as compared to the NC and OT groups (p < 0.0001 and p = 0.0045, respectively) and remained significantly higher in the OT + CSI group after 14 d, compared to the OT group (p < 0.0001). Short-term CSI increases early bone loss in association with OT after 7 d, and this worsens in severity after 14 d of exposure. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

    Science.gov (United States)

    Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

    1993-10-01

    The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

  1. Effects of ethanol and carbon tetrachloride upon vitamin A status of rats

    International Nuclear Information System (INIS)

    McCauley, K.; Prabhudesai, M.; Erdman, J.W. Jr.

    1986-01-01

    The effects of ethanol (ET) and carbon tetrachloride (CCL 4 ) upon tissue vitamin A, liver lipids, liver cytochrome P 450 and hepatic morphology were investigated. After a two week feeding period, young male rats were divided into four groups. For 5 weeks one group of rats (n=18) received ET in liquid diets (30% of calories) while another (n=8) was exposed to CCL 4 inhalation twice a week along with phenobarbitol in the diet. All groups received the NRC recommended level for vitamin A. Comparison of ET and its pair-fed control group revealed; decreased hepatic vitamin A, no change in serum vitamin A, increased % liver lipid and cytochrome P 450 with minimal fat accumulation in hepatocytes. Comparison of CCL 4 group with pair-fed controls showed; increased serum vitamin A, decreased hepatic vitamin A, increased cytochrome P 450 , marked hepatic fat accumulation, hepatic cell necrosis and early cirrhosis. Thus, CCL 4 , which is a more potent hepatotoxin as evidenced by a more elevated cytochrome P 450 and distorted liver morphology, not only reduced liver vitamin A, but also increased serum vitamin A. The hepatic response to CCL 4 may mimic a more cirrhotic condition such as that resulting from longer-termed ET intake

  2. Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of 239Pu inhaled as 239PuO2 by F344 rats

    International Nuclear Information System (INIS)

    Finch, G.L.; Lundgren, D.L.; Barr, E.B.; Chen, B.T.; Griffith, W.C.; Hobbs, C.H.; Hoover, M.D.; Nikula, K.J.; Mauderly, J.L.

    1998-01-01

    As a portion of a study to examine how chronic cigarette smoke exposure might alter the risk of lung tumors from inhaled 239 PuO 2 in rats, the effects of smoke exposure on alpha-particle lung dosimetry over the life-span of exposed rats were determined. Male and female rats were exposed to inhaled 239 PuO 2 alone or in combination with cigarette smoke. Animals exposed to filtered air along served as controls for the smoke exposure. Whole-body exposure to mainstream smoke diluted to concentrations of either 100 or 250 mg total particulate matter m -3 began at 6 wk of age and continued for 6 h d -1 , 5 d wk -1 , for 30 mo. A single, pernasal, acute exposure to 239 PuO 2 was given to all rats at 12 wk of age. Exposure to cigarette smoke caused decreased body weight gains in a concentration dependent manner. Lung-to-body weight ratios were increased in smoke-exposed rats. Rats exposed to cigarette smoke before the 239 PuO 2 exposure deposited less 239 Pu in the lung than did controls. Except for male rats exposed to LCS, exposure to smoke retarded the clearance of 239 Pu from the lung compared to control rats through study termination at 870 d after 239 PuO 2 exposure. Radiation doses to lungs were calculated by sex and by exposure group for rats on study for at least 360 d using modeled body weight changes, lung-to-body weight ratios, and standard dosimetric calculations. For both sexes, estimated lifetime radiation doses from the time of 239 PuO 2 exposure to death were 3.8 Gy, 4.4 Gy, or 6.7 Gy for the control, LCS, or HCS exposure groups, respectively. Assuming an approximately linear dose-response relationship between radiation dose and lung neoplasm incidence, approximate increases of 20% or 80% in tumor incidence over controls would be expected in rats exposed to 239 PuO 2 and LCS or 239 PuO 2 and HCS, respectively

  3. Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration.

    Science.gov (United States)

    Sumner, Susan C J; Janszen, Derek B; Asgharian, Bahman; Moore, Timothy A; Parkinson, Horace D; Fennell, Timothy R

    2003-01-01

    Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD-1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16-71%) or eliminated in urine and feces (28-72%). Following inhalation exposure, mice had a two- to threefold greater relative uptake of [14C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3-dihydroxy-2-methylbutane and glucuronide conjugation of 2,3-dihydroxy-2-methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [14C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P-450 oxidation of TAA was indicated by a disproportional decrease of 2,3-dihydroxy-2-methylbutane and its glucuronide conjugate with increased exposure concentration. Copyright 2003 John Wiley & Sons, Ltd.

  4. Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

    International Nuclear Information System (INIS)

    Zhuang Jianguo; Xu Fadi; Campen, Matthew J.; Zhang Cancan; Pena-Philippides, Juan C.; Sopori, Mohan L.

    2008-01-01

    Sarin, a highly toxic nerve gas, is believed to cause bronchoconstriction and even death primarily through respiratory failure; however, the mechanism underlying the respiratory failure is not fully understood. The goals of this study were to ascertain whether sarin affects baseline ventilation (V E ) and V E chemoreflexes as well as airway resistance and, if so, whether these changes are reversible. Four groups of F344 rats were exposed to vehicle (VEH) or sarin at 2.5, 3.5, and 4.0 mg h m -3 (SL, SM, and SH, respectively). V E and V E responses to hypercapnia (7% CO 2 ) or hypoxia (10% O 2 ) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (R L ) also was measured in anesthetized VEH- and SH-exposed animals 2 h after exposure. Our results showed that within 2 h after exposure 11% of the SM- and 52% of the SH- exposed groups died. Although the SM and SH significantly decreased hypercapnic and hypoxic V E to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline V E (30%; P E impairment recovered within 1-2 days after sarin exposure; interestingly, SH did not significantly affect baseline R L . Moreover, sarin induced body tremors that were unrelated to the changes in the V E responses. Thus, LC 50 sarin causes a reversible impairment of V E that is not dependent on the sarin-induced body tremors and not associated with changes in R L

  5. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    International Nuclear Information System (INIS)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-01-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 μg/m 3 . At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 μg/m 3 , but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 μg/m 3 exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate

  6. Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of β-amyloid in rats.

    Science.gov (United States)

    Bae, Donghyuck; Seol, Heejin; Yoon, Ho-Geun; Na, Ju-Ryun; Oh, Kyonyeo; Choi, Chul Yung; Lee, Dong-wook; Jun, Woojin; Youl Lee, Kwang; Lee, Jeongmin; Hwang, Kwontack; Lee, Yoo-Hyun; Kim, Sunoh

    2012-07-01

    Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system. The aggregation and formation of β-amyloid peptides (Aβ) into fibrils are central events in the pathogenesis of Alzheimer's disease (AD), and overproduction and aggregation of Aβ into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Aβ. To model AD, 4 μg of aggregated Aβ was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. Inhaled EOCO protected spatial learning and memory from the impairments induced by Aβ(1-40) injection. In addition, the behavioral deficits accompanying Aβ(1-40)-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Aβ(1-40) and EOCO compared to rats treated only with Aβ(1-40). EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.

  7. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

    Science.gov (United States)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-09-15

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

  8. Differential electrocardiogram efffects in normal and hypertensive rats after inhalation exposure to transition metal rich particulate matter

    Science.gov (United States)

    Inhalation of particulate matter (PM) associated with air pollution causes adverse effects on cardiac function including heightened associations with ischemic heart disease, dysrhythmias, heart failure, and cardiac arrest. Some of these effects have been attributable to transitio...

  9. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    Science.gov (United States)

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  10. Effect of sulfur dioxide inhalation on CYP2B1/2 and CYP2E1 in rat liver and lung

    Energy Technology Data Exchange (ETDEWEB)

    Guohua Qin; Ziqiang Meng [Shanxi University, Taiyuan (China). Institute of Environmental Medicine and Toxicology

    2006-07-15

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air and in higher concentrations in the working environment. In this study, we investigated the effects of inhaled SO{sub 2} on the O-dealkylase of pentoxyresorufin (PROD) and p-nitrophenol hydroxylases (p-NP) activities and mRNA levels of CYP2B1/2 and CYP2E1 in the lung and liver of Wistar rats. Male Wistar rats were housed in exposure chambers and treated with 14.11 {+-}1.53, 28.36 {+-} 2.12, and 56.25 {+-} 4.28 mg /m{sup 3}SO{sub 2} for 6 h/day for 7 days, while control rats were exposed to filtered air in the same condition. The mRNAs of CYP2B1/2 and -2E1 were analyzed in livers and lungs by using reverse-transcription polymerase chain reaction (RT-PCR). Results showed that the PROD activities and mRNA of CYP2B1/2 were decreased in livers and lungs of rats exposed to SO{sub 2}. The p-NP activities and mRNA of CYP2E1 were decreased in lungs but not in livers of rats exposed to SO{sub 2}. Total liver microsomal cytochrome P-450 (CYP) contents were diminished in SO{sub 2} -exposed rats. These results lead to two conclusions: (1) SO{sub 2} exposure can suppress CYP2B1/2 and CYP2E1 in lungs and CYP2B1/2 in livers of rats, thus modifying the liver and lung toxication/detoxication potential, and (2) the total liver microsomal CYP contents were diminished, although the activity and mRNA expression of CYP2E1 in rat livers were not affected by SO{sub 2} exposure.

  11. NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1997-04-01

    Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean

  12. Toxicological effects of multi-wall carbon nanotubes in rats

    International Nuclear Information System (INIS)

    Liu Aihong; Sun Kangning; Yang, Jiafeng; Zhao Dongmei

    2008-01-01

    The aim of this study was to evaluate the lung toxicity of multi-wall carbon nanotubes (MWCNTs). The present work exposed MWCNTs into the rats in intratracheal instillation administration modes. We systematically studied the distribution of nanoparticles in vivo, target organs and time-effects of nanotoxicity, dose-effects of nanotoxicity, etc. These results indicate that under the conditions of this test, pulmonary exposures to MWCNTs in rats by intratracheal instillation produced a series of multiple lesions in a dose-dependent and time-dependent manner, evidence of a foreign tissue body reaction.

  13. Toxicological effects of multi-wall carbon nanotubes in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu Aihong; Sun Kangning, E-mail: Sunkangning@sdu.edu.cn; Yang, Jiafeng [Engineering Ceramics Key Laboratory of Shandong Province, Material Science and Engineering Institute, Shandong University, Key Laboratory of Liquid Structure and Heredity of Materials ministry of Education (China); Zhao Dongmei [The Second Hospital of Shandong University (China)

    2008-12-15

    The aim of this study was to evaluate the lung toxicity of multi-wall carbon nanotubes (MWCNTs). The present work exposed MWCNTs into the rats in intratracheal instillation administration modes. We systematically studied the distribution of nanoparticles in vivo, target organs and time-effects of nanotoxicity, dose-effects of nanotoxicity, etc. These results indicate that under the conditions of this test, pulmonary exposures to MWCNTs in rats by intratracheal instillation produced a series of multiple lesions in a dose-dependent and time-dependent manner, evidence of a foreign tissue body reaction.

  14. Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

    Science.gov (United States)

    Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

    2015-02-01

    The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

  15. Esculetin Ameliorates Carbon Tetrachloride-Mediated Hepatic Apoptosis in Rats

    Directory of Open Access Journals (Sweden)

    Chuan-Sung Chiu

    2011-06-01

    Full Text Available Esculetin (ESC is a coumarin that is present in several plants such as Fraxinus rhynchophylla and Artemisia capillaris. Our previous study found that FR ethanol extract (FREtOH significantly ameliorated rats’ liver function. This study was intended to investigate the protective mechanism of ESC in hepatic apoptosis in rats induced by carbon tetrachloride. Rat hepatic apoptosis was induced by oral administration of CCl4. All rats were administered orally with CCl4 (20%, 0.5 mL/rat twice a week for 8 weeks. Rats in the ESC groups were treated daily with ESC, and silymarin group were treated daily with silymarin. Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST as well as the activities of the anti-oxidative enzymes glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase in the liver were measured. In addition, expression of liver apoptosis proteins and anti-apoptotic proteins were detected. ESC (100, 500 mg/kg significantly reduced the elevated activities of serum ALT and AST caused by CCl4 and significantly increased the activities of catalase, GPx and SOD. Furthermore, ESC (100, 500 mg/kg significantly decreased the levels of the proapoptotic proteins (t-Bid, Bak and Bad and significantly increased the levels of the anti-apoptotic proteins (Bcl-2 and Bcl-xL. ESC inhibited the release of cytochrome c from mitochondria. In addition, the levels of activated caspase-9 and activated caspase-3 were significantly decreased in rats treated with ESC than those in rats treated with CCl4 alone. ESC significantly reduced CCl4-induced hepatic apoptosis in rats.

  16. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure

    International Nuclear Information System (INIS)

    Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Suarez, Fernando; Roycroft, Joseph H.; Chhabra, Rajendra S.; Bucher, John R.

    2008-01-01

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800 ppm by inhalation, 6 h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800 ppm. Body weight gains were decreased in male rats at 900 and 1800 ppm and in female mice at 1800 ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800 ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800 ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through α2μ-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800 ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800 ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800 ppm, indicating that CPN was increased by mechanisms in addition to those related to α2μ-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800 ppm. The

  17. Effect of long-term inhalation of uranium dust on balance of certain metabolites and enzymes of Krebs cycle on rat kidney tissues

    International Nuclear Information System (INIS)

    Sarsenova, L.K.; Mustafina, R.Kh.

    2010-01-01

    Kidney is the main organ for transportation and cumulation of soluble radioactive nuclides. The changing of bioenergetic processes has the most value for investigation of kidney infringements nature. Purpose of study: exploring the changing dynamics of Krebs cycle dehydrogenases activity and of tricarbonic acid content in rat kidney tissues after long-term inhalation of Uranium ore dust (UOD) for 10 mpc and application of licorice root aqueous solution. The investigation had been performed on winter breeding white out bred male rats which body weight was 120-140 g. UOD inhalation had been conducted in exposure chamber during the 120 days,4 hours per day 5 days per week. Licorice root aqueous solution was injected per os in dose 100 mg/kg 30 days after the inhalation. Isocitric (ICA) and malic acids (MA) were quantified by Hohorost enzymatic method. Activity rate of a-Ketoglutarate, Malat, Succinate and Isocitrate dehydrogenases (AKDG, MDG, SDG, IDG) in the kidney tissue was determined by Kun and Abood method in modification of Oda and Okazaki and Natochin, and assessed by reduction of Neotetrazolium. As control groups intact rats (norm) and intact animals (control) which stood in exposure chamber without UOD 4 hours/day 5 days in week were serving. Each group of 6-10 animals consisted. Data was processed statistically. At UOD inhalation in 10 mpc doze during the first 30 days the ICA content level has decreased more than in 2 times, by 90-th days this indicator has grown in 4 times and has exceeded control on 70 %. By the experiment end for 120 days the level of ICA has decreased, coming nearer to the control. Decrease in concentration of the MA was longer. The decrease maximum - in 2,2 times - has been fixed for 90-s' days of an inhalation. In the subsequent term - to the 120-th day -there was an increase of concentration to the level comparable to the control. Character and depth of radiation influence of the long inhalation of UOD are shown by change of a parity

  18. Deterioration in brain and heart functions following a single sub-lethal (0.8 LCt50) inhalation exposure of rats to sarin vapor:

    International Nuclear Information System (INIS)

    Allon, N.; Chapman, S.; Egoz, I.; Rabinovitz, I.; Kapon, J.; Weissman, B.A.; Yacov, G.; Bloch-Shilderman, E.; Grauer, E.

    2011-01-01

    The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2 ± 1.7 μg/l) for 10 min. About 50% of the rats showed no overt symptoms and the rest had mild to moderate clinical symptoms that subsided within 4 h following exposure. A reduction of weight was noted during the first 3 days with full recovery on the 4th day. Rat's heart was challenged with epinephrine 1 and 6 months post exposure. A significant reduction in the threshold for epinephrine-induced arrhythmia (EPIA) was noted in rats exposed to sarin. A time dependent increase in the kD and Bmax values of muscarinic auto receptors (M2) was recorded in the rat's cortex and striatum. No changes were recorded in the rats' brain trans locator protein (TSPO) levels, concomitant with no observed changes in the animals' performance in A Morris water maze test. A significant increase in open field activity was noted 6 months following exposure to sarin vapor as well as a significant decrease in prostaglandin E 2 (PGE 2 ) production in the brain. It is speculated that down regulation of the M2 auto receptor function, caused hyper reactivity of the cholinergic system which leads to the changes described above. The continuous reduction in M2 auto-receptor system through an unknown mechanism may be the cause for long lasting decline in sarin-exposed casualties' health.

  19. Inhalation of amphotericin B formulations for prevention and treatment of invasive pulmonary aspergillosis : an experimental study in rats

    NARCIS (Netherlands)

    E.J. Ruijgrok (Elisabeth)

    2002-01-01

    textabstractBecause current knowledge of inhalational AMB is limited, a rigorous scientific approach is warranted to establish opt"1mal dose, frequency and durat"1on of administration. We therefore decided to study in detail the fu II potential of nebulised AMB in different formulations, with the

  20. Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein

    NARCIS (Netherlands)

    Cassee, F.R.; Groten, J.P.; Feron, V.J.

    1996-01-01

    Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or

  1. RESPIRATORY EFFECTS OF INHALED METAL-RICH PARTICULATE MATTER (PM) IN RATS: INFLUENCE OF SYSTEMIC ANTIOXIDANT DEPLETION

    Science.gov (United States)

    Metal-mediated generation of reactive oxygen species and resultant oxidative stress has been implicated in the pathogenesis of emission-source PM toxicity. We hypothesized that inducing an antioxidant deficit prior to inhalation of metal-rich PM would worsen adverse health outcom...

  2. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    Science.gov (United States)

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  3. Chronic SO2 inhalation above environmental standard impairs neuronal behavior and represses glutamate receptor gene expression and memory-related kinase activation via neuroinflammation in rats.

    Science.gov (United States)

    Yao, Gaoyi; Yue, Huifeng; Yun, Yang; Sang, Nan

    2015-02-01

    Sulfur dioxide (SO2), as a ubiquitous air pollutant implicated in the genesis of pulmonary disease, is now being considered to be involved in neurotoxicity and increased risk for hospitalization of brain disorders. However, comparatively little is known about the impact of chronically SO2 inhalation on neuronal function. In the present study, by exposing male Wistar rats to SO2 at 3.50 and 7.00 mg/m(3) (approximately 1225 and 2450 ppb, 4.08-8.16 (24h average concentration) times higher than the EPA standard for environmental air concentrations) or filtered air for 90 days, we investigated the impact of chronic SO2 inhalation on performance in Morris water maze, and probed the accompanying neurobiological effects, including activity-regulated cytoskeletal associated gene (Arc) and glutamate receptor gene expression, memory-related kinase level and inflammatory cytokine release in the hippocampus. Here, we found that SO2 exposure reduced the number of target zone crossings and time spent in the target quadrant during the test session in the spatial memory retention of the Morris water maze. Following the neuro-functional abnormality, we detected that SO2 inhalation reduced the expression of Arc and glutamate receptor subunits (GluR1, GluR2, NR1, NR2A, and NR2B) with a concentration-dependent property in comparison to controls. Additionally, the expression of memory kinases was attenuated statistically in the animals receiving the higher concentration, including protein kinase A (PKA), protein kinase C (PKC) and calcium/calmodulin-dependent protein kinaseIIα (CaMKIIα). And the inflammatory cytokine release was increased in rats exposed to SO2. Taken together, our results suggest that long-term exposure to SO2 air pollution at concentrations above the environmental standard in rats impaired spatial learning and memory, and indicate a close link between the neurobiological changes highlighted in the brain and the behavioral disturbances. Copyright © 2014 Elsevier Inc

  4. Biotransformation, distribution and toxicity of carbon disulfide in immature rats

    International Nuclear Information System (INIS)

    Green, E.C.

    1984-01-01

    The 24-hour LD-50 values of CS 2 in 1-, 5-, 10-, 20-, 30-, and 40-day-old rats were 583, 974, 1119, 1545, 1237, and 1183 mg/kg, respectively. Twenty-four hours after CS 2 exposure, decreases in aniline hydroxylation and cytochrome P-450 were observed in rats older than one day of age. Hepatic microsomes from rats of all ages biotransformed CS 2 to COS in vitro in the presence of NADPH. Inhibition of the hepatic mixed-function oxidase enzyme system (HMFOES) was observed after incubation of hepatic microsomes from rats as young as one day of age with CS 2 and NADPH. Studies with radiolabelled CS 2 showed that a covalently binding sulfur metabolite, free from the carbon atom of CS 2 , was formed in vitro during the metabolism of CS 2 to COS which appeared to be responsible for the inhibition of the HMFOES. Three hours after 14 C-CS 2 administration in vivo to rats, between 58 and 83% of the dose of 14 C-CS 2 was expired; 4-9% of the dose was expired as 14 C-CO 2 depending on age. One to 2% of the dose of 14 C-CS 2 , and 1 to 6% of the dose of 35 S-CS 2 remained as biotransformation products in tissues. Biotransformation products of CS 2 were identified as either acid-labile or covalently bound. The results of the study implicated CS 2 biotransformation to sulfur metabolites as an important mechanism of CS 2 toxicity, particularly to 1-day-old rats which had the lowest capacity to eliminate these metabolites

  5. Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat.

    Science.gov (United States)

    Chen, Feng; Wang, LiQin; Chen, ShuJun; Li, ZhiGao; Chen, ZhouLin; Zhou, XinHua; Zhai, Dong

    2014-01-01

    The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 μL of 0.9% normal saline via NI (NS/NI group); 100 μg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 μg of butorphanol alone via NI (B/NI group); and 100 μg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Inhaled /sup 239/PuO/sub 2/ and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.; Lauhala, K.E.; Buschbom, R.L.; Hiastala, M.P.; McGee, D.R.; Park, J.F.; Kuffel, E.G.; Ragan, H.A.; Cannon, W.C.; Yaniv, S.S.; Scott, B.R.

    1988-08-01

    Rats and beagle dogs were given doses of /sup 60/Co gamma radiation and/or body burdens of /sup 239/PuO/sub 2/ within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs.

  7. Inhaled 239PuO2 and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.

    1988-08-01

    Rats and beagle dogs were given doses of 60 Co gamma radiation and/or body burdens of 239 PuO 2 within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs

  8. Blood pharmacokinetics of tertiary amyl methyl ether in male and female F344 rats and CD-1 mice after nose-only inhalation exposure.

    Science.gov (United States)

    Sumner, Susan C J; Janszen, Derek B; Asgharian, Bahman; Moore, Timothy A; Bobbitt, Carol M; Fennell, Timothy R

    2003-01-01

    Interest in understanding the biological behavior of aliphatic ethers has increased owing to their use as gasoline additives. The purpose of this study was to investigate the blood pharmacokinetics of the oxygenate tertiary amyl methyl ether (TAME), its major metabolite tertiary amyl alcohol (TAA) and acetone in rats and mice following inhalation exposure to TAME. Species differences in the area under the curve (AUC) for TAME were significant at each exposure concentration. For rats, the blood TAME AUC increased in proportion with an increase in exposure concentration. For mice, an increase in exposure concentration (100-500 ppm) resulted in a disproportional increase in the TAME AUC. Mice had greater (two- to threefold) blood concentrations of TAA compared with rats following exposure to 2500 or 500 ppm TAME. Mice had a disproportional increase in the TAA AUC with an increase in exposure concentration (100-500 ppm). This difference could result from saturation of a process (e.g. oxidation, glucuronide conjugation) that is involved in the further metabolism of TAA. For each species, gender and exposure concentration, acetone increased during exposure and returned to control values by 16 h following exposure. The source of acetone could be both as a metabolite of TAA or an effect on endogenous metabolism produced by exposure to TAME. Copyright 2003 John Wiley & Sons, Ltd.

  9. Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: Effect on evoked potentials, behaviour and brain neurochemistry

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Ladefoged, Ole; Østergaard, Grete

    2000-01-01

    Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials...... and somatosensory evoked potentials were not affected by TBT In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water...... maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum...

  10. Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1999-02-01

    Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

  11. Effects of a thirteen-week inhalation exposure to ethyl tertiary butyl ether on fischer-344 rats and CD-1 mice.

    Science.gov (United States)

    Medinsky, M A; Wolf, D C; Cattley, R C; Wong, B; Janszen, D B; Farris, G M; Wright, G A; Bond, J A

    1999-09-01

    The 1990 Clean Air Act Amendments require that oxygenates be added to automotive fuels to reduce emissions of carbon monoxide and hydrocarbons. One potential oxygenate is the aliphatic ether ethyl tertiary butyl ether (ETBE). Our objective was to provide data on the potential toxic effects of ETBE. Male and female Fisher 344 rats and CD-1 mice were exposed to 0 (control), 500, 1750, or 5000 ppm of ETBE for 6 h/day and 5 days/wk over a 13-week period. ETBE exposure had no effect on mortality and body weight with the exception of an increase in body weights of the female rats in the 5000-ppm group. No major changes in clinical pathology parameters were noted for either rats or mice exposed to ETBE for 6 (rats only) or 13 weeks. Liver weights increased with increasing ETBE-exposure concentration for both sexes of rats and mice. Increases in kidney, adrenal, and heart (females only) weights were noted in rats. Degenerative changes in testicular seminiferous tubules were observed in male rats exposed to 1750 and 5000 ppm but were not seen in mice. This testicular lesion has not been reported previously for aliphatic ethers. Increases in the incidence of regenerative foci, rates of renal cell proliferation, and alpha2u-globulin containing protein droplets were noted in the kidneys of all treated male rats. These lesions are associated with the male rat-specific syndrome of alpha2u-globulin nephropathy. Increases in the incidence of centrilobular hepatocyte hypertrophy and rates of hepatocyte cell proliferation were seen in the livers of male and female mice in the 5000-ppm group, consistent with a mitogenic response to ETBE. These two target organs for ETBE toxicity, mouse liver and male rat kidney, have also been reported for methyl tertiary butyl ether and unleaded gasoline.

  12. Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

    Science.gov (United States)

    2011-04-01

    Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

  13. Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosa

    International Nuclear Information System (INIS)

    Heck Hd'; Casanova, M.

    1987-01-01

    DNA-protein crosslinks were formed in the nasal respiratory mucosa of Fischer-344 rats exposed for 3 hr to selected concentrations of [ 3 H]- and [ 14 C]formaldehyde ( 3 HCHO and H 14 CHO). In rats depleted of glutathione (GSH) and exposed to 10 ppm of 3 HCHO and H 14 CHO, the 3 H/ 14 C ratio of the fraction of the DNA that was crosslinked to proteins was significantly (39 +/- 6%) higher than that of the inhaled gas. This suggests an isotope effect, either on the formation of DNA-protein crosslinks by labeled HCHO or on the oxidation of labeled HCHO catalyzed by formaldehyde (FDH) or aldehyde dehydrogenase (AldDH). The possibility of an isotope effect on the formation of crosslinks was investigated using rat hepatic nuclei incubated with [ 3 H]- and [ 14 C]formaldehyde (0.1 mM, 37 degrees C). A small (3.4 +/- 0.9%) isotope effect was detected on this reaction, which slightly favored 3 HCHO over H 14 CHO in binding to DNA. The magnitude of this isotope effect cannot account for the high isotope ratio observed in the crosslinked DNA in vivo. The possibility of an isotope effect on the oxidation of 3 HCHO and H 14 CHO catalyzed by FDH was investigated using homogenates of the rat nasal mucosa incubated with [ 3 H]- and [ 14 C]formaldehyde at total formaldehyde concentrations ranging from 0.1 to 11 microM, NAD+ (1 mM), GSH (15 mM), and pyrazole (1 mM). The experiments showed that 3 HCHO is oxidized significantly more slowly than H 14 CHO under these conditions (Vmax/Km (H 14 CHO) divided by Vmax/Km ( 3 HCHO) = 1.82 +/- 0.11). A similar isotope effect was observed in the absence of GSH, presumably due to the oxidation of 3 HCHO and H 14 CHO catalyzed by AldDH

  14. Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

    Science.gov (United States)

    Phillips, Blaine; Titz, Bjoern; Kogel, Ulrike; Sharma, Danilal; Leroy, Patrice; Xiang, Yang; Vuillaume, Grégory; Lebrun, Stefan; Sciuscio, Davide; Ho, Jenny; Nury, Catherine; Guedj, Emmanuel; Elamin, Ashraf; Esposito, Marco; Krishnan, Subash; Schlage, Walter K; Veljkovic, Emilija; Ivanov, Nikolai V; Martin, Florian; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

    2017-11-01

    While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Takao; Iizuka, Tadashi; Kanamori, Takeshi; Yokoyama, Atsuro [Department of Oral Functional Prosthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8586 (Japan); Matsumura, Sachiko; Shiba, Kiyotaka [Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, koutou-ku, Tokyo 135-8550 (Japan); Yudasaka, Masako; Iijima, Sumio, E-mail: tkasai@den.hokudai.ac.jp [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Central 5, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8565 (Japan)

    2011-02-11

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  16. Inhalation of air polluted with gasoline vapours alters the levels of amino acid neurotransmitters in the cerebral cortex, hippocampus, and hypothalamus of the rat.

    Science.gov (United States)

    Kinawy, Amal A; Ezzat, Ahmed R; Al-Suwaigh, Badryah R

    2014-08-01

    This study was designed to investigate the impact of exposure to the vapours of two kinds of gasoline, a widely used fuel for the internal combustion engines on the levels of the amino acid neurotransmitters of the rat brain. Recent studies provide strong evidence for a causative role for traffic-related air pollution on morbidity outcomes as well as premature death (Health Effects Institute, 2009; Levy et al., 2010; von Stackelberg et al., 2013). Exposure to the vapours of gasoline or its constituents may be accidental, occupational by workers at fuel stations and factories, or through abuse as a mean of mood alteration (Fortenberry, 1985; Mc Garvey et al., 1999). Two kinds of gasoline that are common in Egypt have been used in this study. The first contains octane enhancers in the form of lead derivatives (leaded gasoline; G1) and the other contains methyl-tertiary butyl ether (MTBE) as the octane enhancer (unleaded gasoline; G2). The levels of the major excitatory (aspartic acid and glutamic acid) and the inhibitory (GABA and glycine) amino acid neurotransmitters were determined in the cerebral cortex, hippocampus, and hypothalamus. The current study revealed that the acute inhalation of air polluted with the two types of gasoline vapours (1/2 LC50 for 30 min) induced elevation in the levels of aspartic and glutamic acids along with a decrease in glycine and GABA in most studied brain areas. Chronic inhalation of both types of gasoline (a single daily 30-min session of 1/5 LC50 for 60 days) caused a significant increase in the aspartic and glutamic acid concentrations of the hippocampus without affecting the levels of GABA or glycine. Acute and chronic inhalation of either one of G1 and G2 vapours induced a disturbance and fluctuation in the levels of the free amino acids that act as excitatory and inhibitory neurotransmitters in the brain areas under investigation. These neurotransmitters are fundamental for the communicative functioning of the neurons and such

  17. Subacute effects of inhaled Jet Fuel-A (Jet A) on airway and immune function in female rats.

    Science.gov (United States)

    Sweeney, Lisa M; Prues, Susan L; Reboulet, James E

    2013-04-01

    Two studies were conducted to assess the potential airway and immune effects following subacute (14 d) exposure of female rats to 500, 1000 or 2000 mg/m³ of Jet-A for 4 h/d. The first study used Sprague-Dawley rats; the second study included both Fischer 344 (F344) and Sprague-Dawley rats. In the first study, exposure to 2000 mg/m³ jet fuel may have caused significant upper airway inflammation on day 7 post-exposure, as indicated by elevated protein and lactate dehydrogenase in nasal lavage fluid, but any inflammation resolved by day 14 post-exposure. No significant impact on immune cell populations in the spleens was observed. The histological examination showed no evidence of infectious or toxic effect. In the second study, body weights of the F344 rats in the 2000 mg/m³ group were depressed, as compared to the controls, at the end of the exposure. Some lung lavage fluid markers were increased at 24 h after the final exposure, however, no test article-induced histological changes were observed in the lungs, nasal cavities, or any other tissue of any of the jet fuel exposed animals. Overall, these studies demonstrated limited evidence of effects of 14 d of exposure to Jet A on the airways, immune system, or any other organ or system of female Sprague-Dawley and F344 rats, with no remarkable differences between strains. The lack of identified significant airway or immune effects was in contrast to previous examinations of jet fuel for pulmonary toxicity in mice and rats and for immunotoxicity in mice.

  18. Carbon dioxide euthanasia in rats: Oxygen supplementation minimizes signs of agitation and asphyxia

    NARCIS (Netherlands)

    Coenen, A.M.L.; Drinkenburg, W.H.I.M.; Hoenderken, R.; Luijtelaar, E.L.J.M. van

    1995-01-01

    This paper records the effects of carbon dioxide when used for euthanasia, on behaviour, electrical brain activity and heart rate in rats. Four different methods were used. Animals were placed in a box (a) that was completely filled with carbon dioxide; (b) into which carbon dioxide was streamed at

  19. Biological effects of pesticides on rats treated with carbon tetrachloride

    International Nuclear Information System (INIS)

    Abdel Kader, S.M.

    1990-01-01

    The present study investigates the effect of repeated oral doses of the organophosphorus pesticide, cytrolane on normal and pretreated rate with different oral doses of carbon tetrachloride. For that purpose the effect of cytrolane, CCl 4 and their potential interaction had been studied on brain and erythrocyte acetylcholinesterase (Ache), plasma cholinesterase (Ch E), liver succinic dehydrogenase (SDH), serum alkaline phosphatase (SAP), liver succinic dehydrogenas (SDH), serum alkaline phosphatase (SAP), glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminases. It also investigates the effect of an acute oral dose of cytrolane at short time intervals (1/2-24 hours) on brain and blood ache of normal and pretreated rate with a single oral dose of CCl 4 . The distribution and excretion of 1 4cc1 4 at different time intervals (2,6 and 24 hours) in normal rats and in rats pretreated with o.89 mg cytrolane/kg/day for a week had been determined in different organs, expired air, urine and faeces

  20. Gene expression in rat striatum following carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Shuichi Hara

    2017-06-01

    Full Text Available Carbon monoxide (CO poisoning causes brain damage, which is attenuated by treatment with hydrogen [1,2], a scavenger selective to hydroxyl radical (·≡OH [3]. This suggests a role of ·≡OH in brain damage due to CO poisoning. Studies have shown strong enhancement of ·≡OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb level >70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with ·≡OH production [5] might contribute to ·≡OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO database under accession number GSE94780.

  1. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

  2. Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke.

    Science.gov (United States)

    Whitehouse, Michael Wellesley; Jones, Mark

    2009-10-01

    To seek a mechanism linking tobacco smoking with the increased incidence and severity of rheumatoid arthritis, deduced from many retrospective surveys, by studying arthritis/fibrosis development in rats. Rats (>300) received low levels of sodium/potassium thiocyanate (10 or 25 mmol/l) in their drinking water to raise their blood thiocyanate levels, mimicking the elevated levels of blood, salivary and urinary thiocyanate found in smokers. Thiocyanate supplements increased the severity of experimental arthritis induced by tailbase injection of (1) Freund's complete adjuvants (mycobacteria plus various adjuvant-active oils), (2) collagen type-II with Freund's incomplete adjuvant (no mycobacteria), (3) the synthetic lipid amine, avridine in an oil and (4) the natural hydrocarbons squalene (C(30)H(50)) and pristane (C(19)H(40)). This pro-arthritic effect was independent of sex, rat strain or changing diet and housing facilities. Thiocyanate supplements also amplified the acute/persisting inflammatory responses to paw injections of pristane, zymosan and microcrystalline hydroxyapatite. Iodide salts also mimicked some of these effects of thiocyanate. Thiocyanate, a detoxication product of HCN present in tobacco smoke, increased (or even induced) inflammatory responses to several agents causing arthritis or fibrotic inflammation in rats. It, therefore, can act as a co-arthritigen, or 'virulence factor' and could be a therapeutic target to reduce arthritis expression and morbidity.

  3. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    DEFF Research Database (Denmark)

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Zenner

    2011-01-01

    cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation...... and lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring....

  4. Temporary dosal characteristics of processes of Krebs cycle of lungs tissue of rats under prolonged inhalation of uranium dust

    International Nuclear Information System (INIS)

    Bekenova, Zh. M.; Mustafina, R. Kh.; Kazymbet, P. K.

    2010-01-01

    Effect of industrial uranium ore dust (UOD) in extrasmall doses have been studied after prolonged inhalation. It has been established that prolonged inhalation influence of the uranium ore dust (UOD) at the dose equal to 5 threshold limit value (TLV) gradually raised a content of isocitric acid (ICA) - the original product of the Cycle of Tricarbon Acid (NOA). However by the end of the observation already on the 120-th day the peak of increasing ICA started to come down and its indicators exceeded the control level by only 57%. At the same time it has been established that the aqueos licorice root extract facilitates raising a content of ICA which is the product of initial stages in Krebs cycle by 3 times in comparison with the control data and it was by 71% more than under UOD influence. In this case it is the evolution of examined compound ratio, determined as a balance coefficient isocitric acid/malic acid at different periods of UOD effect. It has been identified that at different times of examination its indicators have decreased almost two fold. Also, in the lung tissue of the animals, primed with UOD dose equal to 5 OLV, absolute content of malic acid (MA) practically has not been changing, unless consider the raising of its indicators by 27% and 20% on the 60-th and 120-th days respctively, e.g. in the period of. It has been identified that the licorice root extract has increased concentration indicators of the malic acid in the lung tissue by the average of 4-5%. In this situation particular significance is acquired by dynamics of ratio variation in compounds under investigation determined through a balance coefficient ICA/AA at different periods of UOD effect. It is established that the value of it is lowed by almost 2 times in different terms of observation. Additionally with noticed data in lung tissue activity inhibition of 4-Dehydrogenases in Krebs cycle is revealed. Maximal inhibition is characteristic for Isocitrate- and alphakethoglutarate

  5. Late effects following inhalation of mixed oxide (U,PuO{sub 2}) mox aerosol in the rat; Effets tardifs de l'inhalation d'aerosols de Mox 2,5% ou 7,1% Pu chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, N.; Van Der Meeren, A.; Fritsch, P.; Maximilien, R

    2008-07-01

    Exposure to alpha-emitting particles is a potential long-term health risk to workers in nuclear fuel fabrication plants. Mixed Oxide (MOX: U,PuO{sub 2}) fuels containing low percentages of plutonium obtained from spent nuclear fuels are increasingly employed and in the case of accidental contamination by inhalation or wounds may result in the development of late-occurring pathologies such as lung cancer. However the long term risks particularly with regard to lung cancer are to date unclear. In the case of MOX the risk may indeed be different from that assigned to the individual components, plutonium and uranium. Several factors are influential (i) the dissolution of Pu depends on the physico-chemical properties, for example risk of lung cancer is increased 10 fold after Pu(NO{sub 3}){sub 2} as compared with PuO{sub 2}. (ii) The solubility of Pu is variable whether delivered as PuO{sub 2} or contained within MOX. (iii) The risk of cancer appears to increase with spatial homogeneity of the lung alpha dose. The objective of this study was to investigate the long term effects in rat lungs following MOX aerosol inhalation of similar particle size containing 2.5 or 7.1% Pu. Conscious rats were exposed to MOX aerosols using a 'nose-only' system and kept for their entire life (2-3 years). Different Initial Lung Deposits (ILDs) were obtained using different concentrations of the MOX suspension. Lung total alpha activity was determined in vivo at intervals over the study period by external counting as well as at autopsy in order to estimate the total lung dose. Anatomo-pathological and immunohistochemical analyses were performed on fixed lung tissue after euthanasia. The frequencies of lung pathologies and tumours were determined on lung sections at several different levels. In addition, autoradiography of lung sections was performed in order to assess the spatial localisation of a activity. Inhalation of MOX at ILD ranging from 1-20 kBq resulted in lung

  6. Inhalation of uranium ores

    International Nuclear Information System (INIS)

    Stuart, B.O.; Jackson, P.O.

    1975-01-01

    In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

  7. Short term inhalation toxicity of a liquid aerosol of glutaraldehyde-coated CdS/Cd(OH)2 core shell quantum dots in rats.

    Science.gov (United States)

    Ma-Hock, L; Farias, P M A; Hofmann, T; Andrade, A C D S; Silva, J N; Arnaud, T M S; Wohlleben, W; Strauss, V; Treumann, S; Chaves, C R; Gröters, S; Landsiedel, R; van Ravenzwaay, B

    2014-02-10

    Quantum dots exhibit extraordinary optical and mechanical properties, and the number of their applications is increasing. In order to investigate a possible effect of coating on the inhalation toxicity of previously tested non-coated CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+) was present as impurity), 6h/d for 5 consecutive days. Cd content was determined in organs and excreta after the end of exposure and three weeks thereafter. Toxicity was determined by examination of broncho-alveolar lavage fluid and microscopic evaluation of the entire respiratory tract. There was no evidence for translocation of particles from the respiratory tract. Evidence of a minimal inflammatory process was observed by examination of broncho-alveolar lavage fluid. Microscopically, minimal to mild epithelial alteration was seen in the larynx. The effects observed with coated quantum dots, non-coated quantum dots and CdCl2 were comparable, indicating that quantum dots elicited no significant effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds with larger particle size tested at similarly low concentrations, quantum dots caused much less pronounced toxicological effects. Therefore, the present data show that small particle sizes with corresponding high surfaces are not the only factor triggering the toxic response or translocation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. The occurrence of primary pulmonary neoplasms in rats after inhalation of 147Pm in fused aluminosilicate particles

    International Nuclear Information System (INIS)

    Herbert, R.A.; Scott, B.R.; Hahn, F.F.; Newton, G.J.; Snipes, M.B.; Damon, E.G.; Boecker, B.B.

    1988-01-01

    To determine the biological response following low-energy, beta irradiation of the lung, F344/Crl rats were exposed to aerosols of promethium-147 in fused aluminosilicate particles and observed for their life spans. Radiation pneumonitis and pulmonary fibrosis caused the majority of deaths during the first year after exposure with cumulative doses to the lungs of 210 to 630 Gy. Primary pulmonary neoplasms were responsible for the majority of deaths that occurred beyond 1 yr after exposure and in rats receiving lower cumulative doses to the lung. Hemangiosarcomas and squamous cell carcinomas were the most prevalent pulmonary neoplasms. Three adenocarcinomas were found. The uncorrected crude incidence of primary lung tumors increased with increasing dose to the lung for cumulative doses less than 140 Gy. With higher doses, the incidence declined. Adjusting the data for competing risks eliminated the turnover in the dose-response curve. The times of onset of pulmonary tumors and median survival times were dose-dependent. Rats with higher accumulated radiation doses developed fatal lung tumors at earlier times after exposure. (author)

  9. Inhalation toxicity studies with 1,3-butadiene 3 two year toxicity/carcinogenicity study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Owen, P.E.; Glaister, J.R.; Gaunt, I.F.; Pullinger, D.H.

    1987-05-01

    Groups of 110 male and 110 female CD (Sprague-Dawley) rats were exposed to atmospheres containing 0 (control), 1000 or 8000 ppm v/v butadiene for 6 hr/day and 5 days/week. Ten of each sex from each group were killed at 52 weeks. The study was terminated when it was predicted that survival would drop to 20% to 25%. High dose rats had wet, ruffled fur and showed slight incoordination during the first exposure each week. During the second year, mortality in both treated female groups was increased because of humanitarian sacrifice of animals with large subcutaneous masses, while increased mortality in the high dose males was accompanied by an increase of the severity of nephropathy. Body weight was slightly lower than controls in both sexes at the high dose, but statistically significant only over the first 12 weeks. There were no effects in hematological analyses or tests of neuromuscular function that definitely could be associated with treatment. Liver weights at both doses were increased in both sexes with no associated pathological change. Kidney weight was increased in males at the high dose, together with an increase in the severity of nephrosis. There were increases in the incidences of pancreatic exocrine adenoma; uterine sarcoma; Zymbal gland carcinoma; mammary tumors; thyroid follicular cell tumors; and testis Leydig-cell tumors. These data suggest the butadiene is a weak oncogen to the rat under the conditions of exposure used in this study.

  10. Emotional reactivity to a single inhalation of 35% carbon dioxide and its association with later symptoms of posttraumatic stress disorder and anxiety in soldiers deployed to Iraq.

    Science.gov (United States)

    Telch, Michael J; Rosenfield, David; Lee, Han-Joo; Pai, Anushka

    2012-11-01

    The identification of modifiable predeployment vulnerability factors that increase the risk of combat stress reactions among soldiers once deployed to a war zone offers significant potential for the prevention of posttraumatic stress disorder (PTSD) and other combat-related stress disorders. Adults with anxiety disorders display heightened emotional reactivity to a single inhalation of 35% carbon dioxide (CO(2)); however, data investigating prospective linkages between emotional reactivity to CO(2) and susceptibility to war-zone stress reactions are lacking. To investigate the association of soldiers' predeployment emotional reactivity to 35% CO(2) challenge with several indices of subsequent war-zone stress symptoms assessed monthly while deployed in Iraq. Prospective cohort study of 158 soldiers with no history of deployment to a war zone were recruited from the Texas Combat Stress Risk Study between April 2, 2007, and August 28, 2009. Multilevel regression models were used to investigate the association between emotional reactivity to 35% CO(2) challenge (assessed before deployment) and soldiers' reported symptoms of general anxiety/stress, PTSD, and depression while deployed to Iraq. Growth curves of PTSD, depression, and general anxiety/stress symptoms showed a significant curvilinear relationship during the 16-month deployment period. War-zone stressors reported in theater were associated with symptoms of general anxiety/stress, PTSD, and depression. Consistent with the prediction, soldiers' emotional reactivity to a single inhalation of 35% CO(2)-enriched air before deployment significantly potentiated the effects of war-zone stressors on the subsequent development of PTSD symptoms and general anxiety/stress symptoms but not on the development of depression, even after accounting for the effects of trait anxiety and the presence of past or current Axis I mental disorders. Soldiers' emotional reactivity to a 35% CO(2) challenge may serve as a vulnerability

  11. Interaction of exposure concentration and duration in determining the apoptosis of testis in rats after cigarette smoke inhalation

    Directory of Open Access Journals (Sweden)

    Lijuan He

    2016-07-01

    Full Text Available The effects of differences in smoke concentration and exposure duration in Sprague Dawley rats to determine variation in type and severity of the testis apoptosis were evaluated. The daily dosages were 10, 20 and 30 non-filter cigarettes for a period of 2, 4, 6, 8 and 12 weeks. Mainstream smoke exposure suppressed body weight gain in all regimens. A dose-related increase in plasma nicotine concentration was observed in smoke-exposed groups for 4, 6, 8 and 12 week regimens. Histopathological examination of the exposed groups showed disturbances in the stages of spermatogenesis, tubules atrophying and these appeared to be dose-related. Cytoplasmic caspase-3 immunostaining was detected both in Sertoli cells and germ cells in smoke-exposure groups. An increase in TUNEL-positive cells of testicular cells was observed after 6 weeks of cigarette exposure. The results indicate that cigarette exposure concentration and duration have interaction effect to induce apoptosis in the rat testes.

  12. Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

    Science.gov (United States)

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares; Lepera, José Salvador

    2015-10-01

    Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. NTP Toxicology and Carcinogenesis Studies of Chloroprene (CAS No. 126-99-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-09-01

    Chloroprene is used almost exclusively in the manufacture of neoprene (polychloroprene). Chloroprene was chosen for study because it is a high-volume production chemical with limited information on its carcinogenic potential and because it is the 2-chloro analogue of 1,3-butadiene, a potent, multi-species, multi-organ carcinogen. Male and female F344/N rats and B6C3F1 mice were exposed to chloroprene (greater than 96% pure) by inhalation for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, and B6C3F1 mice (bone marrow cells and peripheral blood erythrocytes). 16-Day Study in Rats: Groups of 10 male and 10 female F344/N rats were exposed to 0, 32, 80, 200, or 500 ppm chloroprene by inhalation, 6 hours per day, 5 days per week, for 16 days. Three 500 ppm males died on day 2 or 3 of the study. Mean body weight gains of 200 ppm males and females and 500 ppm females were significantly less than those of the chamber control groups. On the first day of exposure, rats exposed to 500 ppm were hypoactive and unsteady and had rapid shallow breathing. These effects were also observed to some degree in animals exposed to 200 ppm. After the second day of exposure, the effects in these groups worsened, and hemorrhage from the nose was observed. A normocytic, normochromic, responsive anemia; thrombocytopenia; and increases in serum activities of alanine aminotransferase, glutamate dehydrogenase, and sorbitol dehydrogenase occurred on day 4 in 200 ppm females and 500 ppm males. Kidney weights of 80 and 500 ppm females were significantly greater than those of the chamber control group, as were the liver weights of 200 and 500 ppm females. The incidences of minimal to mild olfactory epithelial degeneration of the nose in all exposed groups of males and females were significantly greater than those in the chamber control groups. The incidence of squamous metaplasia of the respiratory epithelium was

  14. Inhaled ozone (O{sub 3})-induces changes in serum metabolomic and liver transcriptomic profiles in rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC (United States); Karoly, Edward D.; Jones, Jan C. [Metabolon Incorporation, Durham, NC (United States); Ward, William O.; Vallanat, Beena D.; Andrews, Debora L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Schladweiler, Mette C.; Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Bass, Virginia L. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC (United States); Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2015-07-15

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O{sub 3}) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O{sub 3} exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O{sub 3} at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O{sub 3}, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O{sub 3} increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O{sub 3} increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O{sub 3}. In conclusion, short-term O{sub 3} exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia

  15. Repiratory carcinogenesis in rats after inhalation of radioactive aerosols of actinides and lanthanides in various physicochemical forms

    International Nuclear Information System (INIS)

    LaFuma, J.; Nenot, J.C.; Morin, M.; Masse, R.; Metivier, H.; Nobile, D.; Skupinski, W.

    1974-01-01

    To study the role of the distribution of local tissue irradiation on the toxicity of alpha emitters, groups of 50 to 165 rats were exposed to aerosols of 244 Cm(NO 3 ) 3 , 241 Am(NO 3 ) 3 , 238 Pu(NO 3 ) 4 , 235 Pu(NO 3 ) 4 , 239 PuO 2 , and 241 AmO 2 and observed for effects. Curium-244 was most evenly distributed in the lung and most effective in reduction of survival time followed in descending order by 238 Pu(NO 3 ) 4 , 241 Am(NO 3 ) 3 , 241 AmO 2 , 239 Pu(NO 3 ) 4 , and 239 PuO 2 , which was more heterogeneously distributed in the lung as particulate. The toxicity had 2 results: shortening of life span and cancer induction (about 50 percent bronchogenic carcinoma and 40 percent bronchiolo-alveolar carcinomas). There appeared to be no correlation between survival time and cancer induction or localization of the element in the lung and the starting point of the tumors. This histologic type of cancer was independent of the nature of the element. Toxicity and cancer induction appeared to depend on the homogenicity of radiation dose with the more evenly distributed dose being most effective

  16. Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat.

    Science.gov (United States)

    Moallem, Seyed Adel; Mohamadpour, Amir Hooshang; Abnous, Khalil; Sankian, Mojtaba; Sadeghnia, Hamid Reza; Tsatsakis, Aristidis; Shahsavand, Shabnam

    2015-12-01

    Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats.

    Science.gov (United States)

    Boulila, Salha; Elfeki, Abdelfattah; Oudadesse, Hassane; Elfeki, Hafed

    2015-03-01

    This study aimed to investigate the potential effects of a synthetic apatite (carbonated hydroxyapatite) on the detoxification of a group of male "Wistar" rats exposed to nickel chloride. Toxicity was evaluated by rats' bioassay of nickel chloride. Wistar rats received this metal daily by gavage for seven days (4 mg/ml nickel chloride/200 g body weight, BW). To detoxify this organism, a subcutaneous implantation of the apatite is made. The results revealed that exposure to nickel induced oxidative stress, disorders in the balances of ferric phosphocalcic, renal failures, liver toxicity and significant increase in nickel rates in the bones of intoxicated rats. The application of the carbonated hydroxyapatite presented in this study restored those disorders back to normal. The synthetic apatite protected the rats against the toxic effects of nickel by lowering the levels of lipid peroxidation markers and improving the activities of defense enzymes. It also amended ferric and phosphocalcic equilibriums, protected liver and kidney functions and reduced the nickel rate in the bones of the rats. Overall, the results provided strong support for the protective role of carbonated hydroxyapatite in the detoxification of rats exposed to nickel. Those beneficial effects were further confirmed by physico-chemical characterization (X-ray diffraction and infrared spectroscopy), which revealed its property of anionic and cationic substitution, thus supporting its promising candidacy for future biomedical application. The hydroxyapatite is an effective biomaterial to solve health problems, particularly detoxification against metals (nickel).

  18. Efeitos da inalação passiva da fumaça de cigarro sobre as pregas vocais de ratos Effects of passive smoke inhalation on the vocal cords of rats

    Directory of Open Access Journals (Sweden)

    Josilene Luciene Duarte

    2006-04-01

    Full Text Available Poucos estudos demonstram as reações patológicas devidas à inalação de fumaça pelas vias aéreas de ratos. OBJETIVO: Estudar e analisar os possíveis efeitos histopatologicos produzidos pela inalação crônica de fumaça de cigarro nas pregas vocais de ratos. DESENHO DE ESTUDO: Experimental. MATERIAL E MÉTODOS: 36 ratos masculinos (Rattus norvergicus Wistar, de 60 dias de idade, foram mantidos em gaiolas e expostos à inalação da fumaça produzida por 10 cigarros, 3 vezes ao dia, 7 dias por semana, para períodos de 25, 50 e 75 dias, e os controles respectivos. Os animais foram sacrificados e as suas laringes dissecadas e submetidas a análise histológica com coloração de Hematoxilina e Eosina e analisados através de microscopia simples. RESULTADOS: Os ratos expostos ao cigarro exibiram menor (p Few studies have demonstrated the pathologic reactions yielded by smoke inhalation on the airway in rats. AIM: The aim of this study was to analyze the possible histopathological effects produced by chronic cigarette smoke inhalation on the vocal folds of rats. STUDY DESIGN: Experimental. MATERIAL AND METHOD: 36 male rats (Rattus norvergicus Wistar strain, aged 60 days, were kept in cages and exposed to inhalation of the smoke produced by 10 cigarettes lit 3 times a day, 7 days a week, for periods of 25, 50 and 75 days, and their respective controls. Thereafter the animals were killed and their larynxes were dissected and submitted to histological processing for achievement of histological sections, which were stained with Hematoxylin and Eosin and analyzed by light microscopy. RESULTS: The rats exposed to smoke displayed smaller (p< 0,05 body mass than the control group. There was hyperplasia and squamous metaplasia in the free edge of the vocal fold and squamous hyperplasia on the middle portion of the vocal fold in all 3 study periods. Moreover, the 50-day group revealed keratinizing metaplasia in this area. Morphological alterations in

  19. Analysis of toxicity produced by inhalation of trichloroethylene within rat and mice`s respiratory epithelium; Comparazione del danno indotto dall`inalazione di tricloroetilene nell`epitelio nasale e tracheobronchiale del ratto e del topo

    Energy Technology Data Exchange (ETDEWEB)

    Mancuso, M.T.; Fravolini, M.E.; Parasacchi, P.; Lombardi, C.C.; Giovanetti, A. [ENEA, Casaccia (Italy). Area Energia Ambiente e Salute

    1994-05-01

    The aim of this study was to define the sites of cytotoxicity within the respiratory tract (nasal cavity and tracheobronchial tree) after acute inhalation of trichloroethylene (TCE), an organic solvent requiring metabolic activation by cytochrome P-450 enzymatic system to exert its toxic effects. Two animals species, rats and mice, were exposed to 3500 and 7000 ppm of TCE for 30 minutes. The morphological analysis of the respiratory epithelium has underlined a species-specific difference in the cellular sensitivity after treatment with TCE. This work is a part of ENEA (Italian Agency for New Technologies, Energy and the Environment) INTO program, environmental department, sector of effects on man and ecosystem.

  20. Effects of inhalational anaesthesia with low tidal volume ventilation on end-tidal sevoflurane and carbon dioxide concentrations: prospective randomized study.

    Science.gov (United States)

    de la Matta-Martín, M; López-Herrera, D; Luis-Navarro, J C; López-Romero, J L

    2014-02-01

    We investigated how ventilation with low tidal volumes affects the pharmacokinetics of sevoflurane uptake during the first minutes of inhaled anaesthesia. Forty-eight patients scheduled for lung resection were randomly assigned to three groups. Patients in group 1, 2 and 3 received 3% sevoflurane for 3 min via face mask and controlled ventilation with a tidal volume of 2.2, 8 and 12 ml kg(-1), respectively (Phase 1). After tracheal intubation (Phase 2), 3% sevoflurane was supplied for 2 min using a tidal volume of 8 ml kg(-1) (Phase 3). End-tidal sevoflurane concentrations were significantly higher in group 1 at the end of phase 1 and lower at the end of phase 2 than in the other groups as follows: median of 2.5%, 2.2% and 2.3% in phase 1 for groups 1, 2 and 3, respectively (Ptidal carbon dioxide values in group 1 were significantly lower at the end of phase 1 and higher at the end of phase 2 than in the other groups as follows: median of 16.5, 31 and 29.5 mm Hg in phase 1 for groups 1, 2 and 3, respectively (Ptidal volume approximating the airway dead space volume, end-tidal sevoflurane and end-tidal carbon dioxide may not correctly reflect the concentration of these gases in the alveoli, leading to misinterpretation of expired gas data. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  1. Effects of active inhalation of trichloroethylene on rat respiratory tract; Andamento della deposizione e della clearance respiratoria nel ratto di un aerosol insolubile in seguito ad inalazione acuta di tricloroetilene

    Energy Technology Data Exchange (ETDEWEB)

    Calamosca, M.; Pettinato, G. [ENEA, Bologna (Italy). Area Energia Ambiente e Salute

    1994-05-01

    The effects of an acute inhalation of tricloroethylene (TCE) on the rat respiratory tract have been investigated. In a previous work on mice, the observed damage proved to be limited to Clara cells (CC) and dose-dependent. Injury was correlated with the metabolic properties of CC, where TCE is converted to toxic intermediate metabolites. Since rat CC are located in the distal bronchial tree, a damage at this level is supposed to affect also the mechanical clearance of insoluble particles. Sprague-Dawley, female rats have been exposed for 30min, to a co 30min, to a concentration of 3500 ppm TCE, to investigate the occurrence of an impairment of the mucous-ciliary/alveolar macrophagic (AM) removal system eventually correlated with epithelial damage, whose results are presented in a different pubblication. Nasopharyngeal and bronchopulmonary clearance patterns were obtained from the retention of a radio-labeled carnauba wax control aerosol (0.70 mim CMAD, Sg < 1.08), the rats inhaled 24 h after esposure to TCE. Sequential sacrifices, close together in time, were performed up to 24 h to detect the rapid clearance phase in all the different regions of the respiratory tract; from then on the retention was assessed by in vivo measuring the rats up to 600 h. A new mechanistic model has been designed and applied to the retention data, to achieve the parameters of relative deposition and the rates of clearance. The statistical comparison of the parameter was carried over by means of the bootstrapping method. Even if a major deposition in the bronchial region of the TCE test occurs, no significant differences have been detected between all the parameters describing the clearance both of the bronchoalveolar and nasopharyngeal regions; neither the fraction of sequestered particles in the upper respiratory tract nor the laden AM particles transferred by the mucociliary escalator were significantly different compared with the control test.

  2. Contribution of time-activity pattern and microenvironment to black carbon (BC) inhalation exposure and potential internal dose among elementary school children

    Science.gov (United States)

    Jeong, Hyeran; Park, Donguk

    2017-09-01

    The aims of this study were to quantify the contributions of activities or microenvironments (MEs) to daily total exposure to and potential dose of black carbon (BC). Daily BC exposures (24-h) were monitored using a micro-aethalometer micoAeth AE51 with forty school-aged children living in an urban area in Korea from August 2015 to January 2016. The children's time-activity patterns and the MEs they visited were investigated by means of a time-activity diary (TAD) and follow-up interviews with the children and their parents. Potential inhaled dose was estimated by multiplying the airborne BC concentrations (μg/m3) we monitored for the time the children spent in a particular ME by the inhalation rate (IR, m3/h) for the time-activity performed. The contribution of activities and MEs to overall daily exposure to and potential dose of BC was quantified. Overall mean daily potential dose was equal to 24.1 ± 10.6 μg/day (range: 6.6-46.3 μg/day). The largest contribution to BC exposure and potential dose (51.9% and 41.7% respectively) occurred in the home thanks to the large amount of time spent there. Transportation was where children received the most intense exposure to (14.8%) and potential dose (20.2%) of BC, while it accounted for 7.6% of daily time. School on weekdays during the semester was responsible for 20.3% of exposure and 22.5% of potential dose. Contribution to BC exposure and potential dose was altered by several time-activity parameters, such as type of day (weekdays vs. weekends; school days vs. holidays), season, and gender. Traveling by motor vehicle and subway showed more elevated exposure or potential dose intensity on weekdays or school days, probably influenced by the increased surrounding traffic volumes on these days compared to on weekends or holidays. This study may be used to prioritize targets for minimizing children's exposure to BC and to indicate outcomes of BC control strategies.

  3. Radioimmunoassay of rat carbonic anhydrases I and II. Application to central nervous system during ontogenesis

    International Nuclear Information System (INIS)

    Limozin, Nicole; Filippi, Danielle; Dalmasso, Christiane; Laurent, Georgette

    1979-01-01

    A specific radioimmunoassay method for rat erythrocyte carbonic anhydrases I and II was developed using a double antibody system. Its sensitivity was in the nanogram range for each of the two isozymes. The method has been applied to the assay of cerebral carbonic anhydrase. Only CAII has been found in brain extracts of perfused rats. Accordingly, the assay of CAI in cerebral tissue can be used to quantify erythrocyte contamination on condition that the ratio CAII/CAI in blood had been worked out. The developmental change in the soluble and the Triton X-100 solubilized brain CAII from birth to adult is reported [fr

  4. Inhalation Therapy in Horses.

    Science.gov (United States)

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Influence of inhaled Ca-DTPA on the long-term effects of inhaled Pu nitrate

    International Nuclear Information System (INIS)

    Ballou, J.E.; Dagle, G.E.; McDonald, K.E.; Buschbom, R.L.

    1975-01-01

    Inhaled Ca-DTPA administered to rats in 6 weekly, one-hour treatments of 3 mg/rat did not affect weight gain or life-span compared to Pu burdened animals (78 nCi ILB) or nontreated controls. In addition, the drug did not appear to promote the development of malignant lung tumors and bone tumors in Pu burdened rats although one rat exposed only to Ca-DTPA aerosols did develop a malignant lung tumor. This single lung tumor can not be considered significant although the normal incidence of this lesion is quite low. Inhaled Ca-DTPA therapy administered 20 days after Pu inhalation showed little effect in reducing the lung burden of plutonium. Skeletal deposition was decreased possibly because Ca-DTPA was administered during a time of active translocation of the inhaled Pu when Pu may have been available for chelation in the blood. Inhaled Ca-DTPA therapy did not appear to be beneficial in reducing the number of malignant lung tumors or bone tumors in plutonium burdened rats but on the other hand the chelate did not appear to promote these lesions. (U.S.)

  6. The cardiac effects of carbon nanotubes in rat

    Directory of Open Access Journals (Sweden)

    Mina Hossein Pour

    2016-06-01

    Conclusion: Injection of CNTs in rats resulted in increase of heart rate. The reason of phenomenon is that multiwall CNTs may block potassium channels. The suppressed and inhibited IK and potassium channels lead to increase of heart rate.

  7. Constant infusion of 15O-labeled water and inhalation of 11C-labeled carbon monoxide for the regional determination of pulmonary water by positron emission tomography

    International Nuclear Information System (INIS)

    Meyer, G.J.; Schober, O.; Hundeshagen, H.

    1983-01-01

    A method was developed for the continuous infusion of 15 O-labeled water which allows the tomographic reconstruction of the total lung water (TLW). Subsequent inhalation of 11 C-labeled carbon-monoxide permits the reconstruction of the blood volume (BV). After normalization of intravascular activities the difference of TLW minus BV yields a quantitative value of regional extravascular lung water (rELW). 15 O-O 2 is converted on-line to 15 O-H 2 O and trapped in a 2 ml buffer reservoir which is fed by a pump with 0.9% NaCl. A precision pump is used to withdraw the labeled H 2 O and infuse it at a rate of 6 ml/min. The radioactivity level of the indusate (ca. 3.7 MBq/sec) is controlled and can be kept constant with a deviation of less than 5% over 40 min. The sterility and apyrogenicity of the system effluent is assured by frequent bacteriological, rabbit and limulus tests. A constant radioactivity level in the lung area is reached after 8-10 min. The infusion is continued for the tomographic reconstruction (Positron Camera System 4200, Cyclotron Corp.) which takes 15 min. A fast change of cyclotron parameters (MC-36, Scanditronix) and automated chemistry procedures allow a single breath administration of 11 C-CO (ca. 40 MBq) 15 min after the end of the 15 O-H 2 O infusion. Blood pool equilibrium is reached after 3-4 min, and the blood volume is reconstructed within 15 min also. Intravascular activites as determined from reconstructed slices in the region of the aortic arch correlate linearly with blood sample activities up to 100 kBq/ml. (orig.) [de

  8. Ciclesonide Oral Inhalation

    Science.gov (United States)

    ... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

  9. Flunisolide Oral Inhalation

    Science.gov (United States)

    ... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

  10. Hydrazine inhalation hepatotoxicity.

    Science.gov (United States)

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

  11. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  12. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  13. Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

    International Nuclear Information System (INIS)

    Inaji, Motoki; Okauchi, Takashi; Nagai, Yuji; Nojima, Kumie; Suhara, Tetsuya

    2004-01-01

    The present study was designed to make a new Parkinson disease model using carbon ion beam. In this year, we irradiated right middle forebrain bundle of adult rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars which was developed in this year. In 4 weeks after the irradiation, we performed methamphetamine induced rotation test and the autoradiography measurement on dopamine transporter using [ 11 C]PE2I to assess degeneration of dopaminergic neurons in caudate putamen (Cpu). As a result, ipsilateral rotation was observed and the distributions of dopamine transporter in the striatum decreased significantly. These results are similar to those of 6-OHDA lesioned rats, and indicate validity of this model. (author)

  14. A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice.

    Science.gov (United States)

    Mattie, D R; Alden, C L; Newell, T K; Gaworski, C L; Flemming, C D

    1991-01-01

    The kerosene-type jet fuel, JP-8, consists of a complex mixture of aliphatic and aromatic hydrocarbons. Because of the utility of JP-8, studies have been conducted to identify the potential long-term consequence of occupational inhalation exposure. Fischer 344 rats and C57BL/6 mice of both sexes were exposed to JP-8 vapors at 0, 500, and 1,000 mg/m3 on a continuous basis for 90 days, then followed by recovery until approximately 24 months of age. Occurrence of necrotizing dermatitis associated with fighting resulted in an increase in mortality in mice (male greater than female) during the 2 week to 9 month post-exposure recovery period. The male rat kidney developed a reversible ultrastructural increase in size and propensity for crystalloid changes of phagolysosomal proteinic reabsorption droplets in the proximal convoluted tubular epithelium. A specific triad of persisting light microscopic renal lesions occurred but functional change was limited to a decrease in urine concentration compared to controls that persisted throughout the recovery period. The response is comparable to the chronic effect of lifetime exposure of the male rat to unleaded gasoline, d-limonene, and p-dichlorobenzene, except for the absence of tubular tumorigenesis. The active toxicologic response presumably must occur over a greater proportion of the male rat's life span for the tumor component of this male rat hydrocarbon nephropathy syndrome. The predictiveness for humans must be questioned, since the pathologic response to JP-8 involved only one tissue in one sex of one species, and since the male rat response appears to be linked to an inherent renal protein peculiarity.

  15. Effect of Carbonated Beverage Intake on Blood Gases and Some Biochemical Parameters in Male Albino Rats

    International Nuclear Information System (INIS)

    Taha, M.S.; Osman, H.F.

    2012-01-01

    The purpose of this study was to identify the effect of carbonated beverage (colourless or black coloured drinks) on arterial blood gases, kidney function, bone mineral density (BMD), glucose and insulin. The rats were divided into three groups; ten rats per each group. Group (I) used as control, group (II) rats supplemented with colourless carbonated beverage (10 ml /100 ml water) and group (III) rats supplemented with black coloured carbonated beverage (10 ml /100 ml water) for three months. The arterial blood gases were evaluated by measuring ph PO 2 , , PCO 2 , , H + a nd HCO 3 -. Rats receiving the coloured drinks showed high significant increase in ph while PO 2 showed very high significant decrease in both groups. PCO 2 showed high significant decrease in groups (II) and (III) while H + showed high significant decrease in group (III) only. HCO 3 - showed high significant increase in group III. All these changes were related to carbonic acid dissolved in water and the increased ph lead to alkalinity of the blood and it is inversely proportional to the number of hydrogen ions (H + ). Non-significant changes were observed in sodium ions while potassium ions showed significant increase in group (II) and high significant increase in group (III). The level of urea showed high and very high significant increase in groups (II) and (III), respectively. Creatinine level showed non-significant increase in group (III). The histopathology changes were observed in kidney tissues in rats of groups (II) and (III). From these results, it appears that black coloured beverage can increase the risk of kidney problems more than colourless beverages. Ca + and inorganic phosphorous levels showed non- significant change except Ca ions showed a significant decrease in rats of group (III). The acidity of carbonated beverage leads to weak bones by promoting the loss of calcium. The decrease of bone mineral density was more pronounced in some parts of femur of rats receiving black

  16. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

  17. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    International Nuclear Information System (INIS)

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-01-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl 4 ) at day 6. Andrographolide pretreatment suppressed CCl 4 -induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in

  18. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    Science.gov (United States)

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Assessing inhalation injury in the emergency room

    Directory of Open Access Journals (Sweden)

    Tanizaki S

    2015-07-01

    Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

  20. Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

    DEFF Research Database (Denmark)

    Folkmann, Janne Kjærsgaard; Vesterdal, Lise Kristine; Sheykhzade, Majid

    2012-01-01

    Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (...

  1. Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

    Science.gov (United States)

    Borm, Paul J A; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; van Schooten, Frederik Jan; Oberdörster, Günter; Schins, Roel P F

    2005-06-01

    The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely.

  2. Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks

    International Nuclear Information System (INIS)

    Borm, Paul J.A.; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; Schooten, Frederik Jan van; Oberdoerster, Guenter; Schins, Roel P.F.

    2005-01-01

    Objective: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. Methods: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m 3 ). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 μM) and a mixture of 16 PAHs (0.1 μM) were used. Results: No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 μg/cm 2 ) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. Conclusion: The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely

  3. Inhalant allergies in children.

    Science.gov (United States)

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Inhalant Abuse and Dextromethorphan.

    Science.gov (United States)

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Antihepatotoxic effect of golden berry (Physalis peruviana Linn.) in carbon tetrachloride (CCl4) intoxicated rats.

    Science.gov (United States)

    Taj, Darakhshan; Khan, Hira; Sultana, Viqar; Ara, Jehan; Ehteshamul-Haque, Syed

    2014-05-01

    Liver is the main site in the body for intense metabolism and excretion. A number of chemicals and drugs which are used routinely cause liver damage. The present study investigates the antihepatotoxic effect of Physalis peruviana whole ripe fruit, water and ethanol extracts of fruit in normal as well as in carbon tetrachloride (CCl(4)) intoxicated rats. The CCl(4) treated rats showed marked elevation in liver enzymes: alanine transaminse, aspratate transaminase, alkaline phosphatase, lactate dehydrogenase and other biochemical parameters: bilirubin, creatinine and urea, thus indicating liver injury. Whereas animal treated/fed with various preparations of Physalis peruviana showed significant lowering effect (pPhysalis peruviana showed highest activity in both rat models while ripe fruit and ethanol extract showed moderate activity compared to standard drug.

  6. [Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

    2018-04-25

    The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

  7. Detoxification of rats subjected to nickel chloride by a biomaterial-based carbonated orthophosphate.

    Science.gov (United States)

    Boulila, S; El Feki, A; Oudadesse, H; Kallel, C; El Feki, H

    2014-09-01

    Recently, the therapeutic approaches of the detoxification against the metals (nickel) in the body are the use of biomaterials such as carbonated hydroxyapatite. The aim of this study is therefore to analyze the physiological and physicochemical parameters of strain white rats "Wistar" receiving nickel chloride and to study the protective associative of apatite against adverse effects of this metal, and this in comparison with control rats. Our results showed that the nickel induced in rats an oxidative stress objectified by elevated levels of thiobarbituric acid-reactive substances and conjugated dienes associated with inhibition of the activity of the antioxidant defense system such as glutathione peroxidase, superoxide dismutase and catalase in the liver, kidney, spleen and erythrocyte. Disorders balances of ferric, phosphocalcic, a renal failure and a liver toxicity were observed in rats exposed to nickel. As well as a significant increase in the rate of nickel in the bones and microcytic anemia was revealed. However, the implantation of carbonated hydroxyapatite in capsule form protects rats intoxicated by the nickel against the toxic effects of this metal by lowering the levels of markers of lipid peroxidation and improving the activities of defense enzymes. Our implantation technique is effective to correct ferric balance and phosphocalcic equilibrium, to protect liver and kidney function, to reduce the rate of bone nickel and to correct anemia. They clearly explain the beneficial and protective of our biomaterial which aims the detoxification of rats receiving nickel by substituting cationic (Ca(2+) by Ni(2+)) and anionic (OH(-) by Cl(-)) confirmed by physicochemical characterization like the IR spectroscopy and X-ray diffraction. These techniques have shown on the one hand a duplication of OH(-) bands (IR) and on the other hand the increase of the volume of the apatite cell after these substitutions (X-ray diffraction). Copyright © 2014 Elsevier Masson

  8. Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection.

    Science.gov (United States)

    Noguchi, Tadashi; Kamigaito, Tomoyuki; Katagiri, Taku; Kondou, Hitomi; Yamazaki, Kazunori; Aiso, Shigetoshi; Nishizawa, Tomoshi; Nagano, Kasuke; Fukushima, Shoji

    2013-01-01

    Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo.

  9. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats.

    Science.gov (United States)

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1μM which peaked at 30min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (pandrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl4) at day 6. Andrographolide pretreatment suppressed CCl4-induced plasma aminotransferase activity and hepatic lipid peroxidation (pandrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats

    Science.gov (United States)

    Jaji, Alhaji Zubair; Zakaria, Zuki Abu Bakar; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Abba, Yusuf; Isa, Tijani; Mahmood, Saffanah Khuder

    2017-05-01

    Calcium carbonate nanoparticles have shown promising potentials in the delivery of drugs and metabolites. There is however, a paucity of information on the safety of their intentional or accidental over exposures to biological systems and general health safety. To this end, this study aims at documenting information on the safety of subcutaneous doses of biogenic nanocrystals of aragonite polymorph of calcium carbonate derived from cockle shells (ANC) in Sprague-Dawley (SD) rats. ANC was synthesized using the top-down method, characterized using the transmission electron microscopy and field emission scanning electron microscope and its acute and repeated dose 28-day trial toxicities were evaluated in SD rats. The results showed that the homogenous 30 ± 5 nm-sized spherical pure aragonite nanocrystals were not associated with mortality in the rats. Severe clinical signs and gross and histopathological lesions, indicating organ toxicities, were recorded in the acute toxicity (29,500 mg/m2) group and the high dose (5900 mg/m2) group of the repeated dose 28-day trial. However, the medium- (590 mg/m2 body weight) and low (59 mg/m2)-dose groups showed moderate to mild lesions. The relatively mild lesions observed in the low toxicity dosage group marked the safety margin of ANC in SD rats. It was concluded from this study that the toxicity of CaCO3 was dependent on the particulate size (30 ± 5 nm) and concentration and the route of administration used.

  11. Effects of halothane-nitrous oxide inhalation anesthesia and Inactin on overall renal and tubular function in Sprague-Dawley and Wistar rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Christensen, P; Leyssac, P P

    1982-01-01

    Real function, plasma renin concentration (PRC) and prostaglandin (PG) excretion rate was studied in groups of Sprague-Dawley (SPRD) and Wistar (WIST) rats anesthetized with either Halothane-N2O or Inactin. Conscious rats were used as controls. A. In Halothane-N2O anesthesia inulin clearance (CIN...... anesthesia indicating that the proximal luminal diameter was constant and independent of CIN. B. Inactin anesthesia CIN was similarly reduced but APR was more depressed (by about 35%). RPF and solute excretion rate decreased only in SPRD rats, while urine flow was significantly reduced in both strains. 1/OT...... prepared rats are more severely depressed by Inactin than by Halothane-N2O anesthesia. The gas anesthesia is equally well tolerated by both strains of rats....

  12. Objective measurement of inhaler inhalation flow profile using acoustic methods

    Energy Technology Data Exchange (ETDEWEB)

    Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

    2016-07-01

    Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

  13. Influence of multi-walled carbon nanotubes on the cognitive abilities of Wistar rats

    Science.gov (United States)

    Sayapina, Nina V.; Sergievich, Alexander A.; Kuznetsov, Vladimir L.; Chaika, Vladimir V.; Lisitskaya, Irina G.; Khoroshikh, Pavel P.; Batalova, Tatyana A.; Tsarouhas, Kostas; Spandidos, Demetrios; Tsatsakis, Aristidis M.; Fenga, Concettina; Golokhvast, Kirill S.

    2016-01-01

    Studies of the neurobehavioral effects of carbon nanomaterials, particularly those of multi-walled carbon nanotubes (MWCNTs), have concentrated on cognitive effects, but data are scarce. The aim of this study was to assess the influence of MWCNTs on a number of higher nervous system functions of Wistar rats. For a period of 10 days, two experimental groups were fed with MWCNTs of different diameters (MWCNT-1 group, 8–10 nm; MWCNT-2 group, 18–20 nm) once a day at a dosage of 500 mg/kg. In the open-field test, reductions of integral indications of researching activity were observed for the two MWCNT-treated groups, with a parallel significant (Ptest, integral indices of researching activity in the MWCNT-1 and MWCNT-2 groups reduced by day 10 by 51 and 62%, respectively, while rat stress levels remained relatively unchanged. In the universal problem solving box test, reductions in motivation and energy indices of researching activity were observed in the two experimental groups. Searching activity in the MWCNT-1 group by day 3 was reduced by 50% (Ptests demonstrated that MWCNT-treated rats experienced a significant reduction of some of their cognitive abilities, a disturbing and worrying finding, taking into consideration the continuing and accelerating use of carbon nanotubes in medicine and science. PMID:27588053

  14. Fasting ameliorates metabolism, immunity, and oxidative stress in carbon tetrachloride-intoxicated rats.

    Science.gov (United States)

    Sadek, Km; Saleh, Ea

    2014-12-01

    Fasting has been recently discovered to improve overall health, but its beneficial effects in the presence of hepatic insufficiency have not been proven. The influence of fasting on the metabolism, immunological aspects, and oxidative stress of 40 male carbon tetrachloride (CCl4)-intoxicated Wistar rats was investigated in the present study. The rats were divided into four groups, including a placebo group, CCl4-intoxicated rats, which were injected subcutaneously with 1.0 ml/kg of CCl4 solution, a fasting group, which was fasted 12 h/day for 30 days, and a fourth group, which was injected with CCl4 and fasted. The metabolism, immunity, and oxidative stress improved in CCl4-intoxicated rats fasted for 12 h/day for 30 days, as evidenced in significant increase (p fasting improved metabolism, immunity, and oxidative stress in CCl4-intoxicated rats. Thus, fasting during Ramadan is safe for patients with hepatic disorders, as the prophet Mohammed (S) said "Keep the fast, keep your health". © The Author(s) 2014.

  15. Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Takagi Tomohisa

    2012-09-01

    Full Text Available Abstract Background The pathogenesis of inflammatory bowel disease (IBD is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS in rats. Methods Acute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA-reactive substances, tissue-associated myeloperoxidase (MPO activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC-1 in colonic mucosa 7 days after TNBS administration. Results The administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas. Conclusions Colonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.

  16. Solanum muricatum Aiton Juice as A Hepatoprotective Agent in Wistar Rats Induced With Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    Justine Sim Wei Yang

    2015-12-01

    Full Text Available Background: Liver participates in various metabolic processes in human body. Exposures to toxins such as carbon tetrachloride (CCl4 results in hepatocyte destruction and release the cell contents. Enzymes such as serum glutamic pyruvic transaminase (SGPT were used as a parameter to diagnose liver damage. Pepino (Solanum muricatum Aiton contains antioxidants that protect liver from hepatoxicity. The aim of this experiment is to determine the effect of pepino in protecting the hepatocyte from hepatotoxic effect of CCl4. Methods: A total of 16 Wistar rats used as the subject were divided into Control and Therapeutic Group. The Control group was induced with CCl4 but was not given pepino juice. Meanwhile, the Therapeutic Group was given pepino juice for 10 days. For induction of hepatotoxicity, CCl4 10% was given at a dosage of 2.0 ml/kg intra-peritoneal. Each Wistar rat in Therapeutic Group was given 1.0 ml of 300 g/ml pepino juice via oral feeding. Spectrophotometer with adjusted wavelength of 340 nm was used to measure SGPT level of the Wistar rats and statistical T-test was used to analyze the data. Results: Wistar rats in Therapeutic group showed a larger decrease (6898.9 IU/L–79.1 IU/L in SGPT level compared to the Control group (6469.8 IU/L–418.5 IU/L. The SGPT level of the Wistar rat in Therapeutic group reached normal baseline (50 IU/L–150 IU/L. The significance of the experiment was supported by the T-test, P-value <0.05 Discussion: Pepino juice had antioxidants that protect the hepatocyte of Wistar rats from free radicals. The synergistic action of antioxidants and hepatocyte regeneration of Wistar rats in Therapeutic group caused a decrease in SGPT level. Therefore, the experiment concluded that pepino juice at the dosage of 300 g/ml has hepatoprotective effect.

  17. A method for calculating the gas volume proportions and inhalation temperature of inert gas mixtures allowing reaching normothermic or hypothermic target body temperature in the awake rat

    Directory of Open Access Journals (Sweden)

    Jacques H Abraini

    2017-01-01

    Full Text Available The noble gases xenon (Xe and helium (He are known to possess neuroprotective properties. Xe is considered the golden standard neuroprotective gas. However, Xe has a higher molecular weight and lower thermal conductivity and specific heat than those of nitrogen, the main diluent of oxygen (O2 in air, conditions that could impair or at least reduce the intrinsic neuroprotective properties of Xe by increasing the critical care patient's respiratory workload and body temperature. In contrast, He has a lower molecular weight and higher thermal conductivity and specific heat than those of nitrogen, but is unfortunately far less potent than Xe at providing neuroprotection. Therefore, combining Xe with He could allow obtaining, depending on the gas inhalation temperature and composition, gas mixtures with neutral or hypothermic properties, the latter being advantageous in term of neuroprotection. However, calculating the thermal properties of a mixture, whatever the substances – gases, metals, rubbers, etc. – is not trivial. To answer this question, we provide a graphical method to assess the volume proportions of Xe, He and O2 that a gas mixture should contain, and the inhalation temperature to which it should be administered to allow a clinician to maintain the patient at a target body temperature.

  18. Inhalants in Peru.

    Science.gov (United States)

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  19. Protective effects of pomegranate (Punica granatum) juice on testes against carbon tetrachloride intoxication in rats.

    Science.gov (United States)

    Al-Olayan, Ebtesam M; El-Khadragy, Manal F; Metwally, Dina M; Abdel Moneim, Ahmed E

    2014-05-22

    Pomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl4)-induced oxidative stress and testes injury in adult Wistar rats. Twenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl4 (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl4 treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl4-induced reproductive toxicity in rats. Pomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl4. Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were restored with the treatment of pomegranate juice. The results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.

  20. Protective effects of pomegranate (Punica granatum) juice on testes against carbon tetrachloride intoxication in rats

    Science.gov (United States)

    2014-01-01

    Background Pomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl4)-induced oxidative stress and testes injury in adult Wistar rats. Methods Twenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl4 (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl4 treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl4-induced reproductive toxicity in rats. Results Pomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl4. Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were restored with the treatment of pomegranate juice. Conclusion The results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated

  1. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, U; Brand, K

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

  2. Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ehsan Zayerzadeh

    2016-07-01

    Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

  3. Evaluation of porous vitreous carbon or silicon implants by radiology in rat's skull

    International Nuclear Information System (INIS)

    Vaccari-Mazzetti, Marcelo Paulo; Kobata, Celio Toshiro; Fabiani, Paulo; Martins, Dulce Maria Fonseca Soares; Gomes, Paulo de Oliveira; Martins, Jose Luiz

    2008-01-01

    Purpose: Evaluate by CT the use of porous vitreous carbon (PVC) and silicon (S) implants as the replacement bone in the craniofacial skeleton of rats. Methods: 40 rats divided in: Group A (n=20) PVC submitted to the implant of a fragment in skull. After the euthanasia, the animals were divided into two subgroups: A I: 10 animals, studied in the 7th postoperative day (P.O) and AII: 10 animals, studied in the 28th P.O. In group B, S, 20 rats were submitted to S implant in the skull. All other steps were identical to group A, with designation of subgroups BI and BII. CT with beams in axial cuts of 1 mm thickness to obtain 3-D information It was used Hounsfield scale for evaluate the radio density of the implant. They were used non parametric tests to analyze the results. Results: The 7th PO boss remained in the two groups, but for 28th PO, observed reduction in the volume of the implant in Group A, not observed in group B. CT studies noticed different radio densities around all of S prostheses (pseudo capsule), that do not appeared in CPV implants. The S has remained unchanged in the CT, but the CPV has had a modification in its radio density (p≤0,05), in all implants. Conclusion: In CT evaluation the implants of CPV have greater deformation that the S, which makes them not suitable for replacement of membranous bone in the rat skull. (author)

  4. Dietary Antioxidants Effectiveness on Carbon Tetrachloride-Induced Hepatotoxicity in Adult Female Albino Rats

    International Nuclear Information System (INIS)

    EI-Sherbiny, E.M.; EI-Mahdy, A.A.

    2008-01-01

    Hepatic toxicity through carbon tetrachloride (CCI 4 ) induced lipid peroxidation was extensively used in experimental models to understand the cellular mechanisms behind oxidative damage and to evaluate the therapeutic potential of drugs and dietary antioxidants. The ameliorative effect of Aloe vera juice and carrot supplementation on hepato carcinogenesis induced by carbon tetrachloride in adult female albino rats was investigated. The carcinogenic process was determined by measuring gamma-glutamyl transpeptidase (GGT), ornithine carbamyl transferase (OCT), thiobarbituric acid reactive substances (TBARs), representing levels of lipid peroxides, and carcinoembryonic antigen (CEA) in the sera of female albino rats. Carbon tetrachloride significantly elevated the serum GGT, OCT activities and the level of TBARs. Administration of Aloe vera leaf juice filtrate after CCl 4 treatment resulted in a non-significant modification in GGT, OCT activities and significantly improved the level of TBARs in comparison with control. Supplementation of carrot to CCI 4 treated animals led to a great amelioration in OCT activity and TBARs level, whereas GGT activity was ameliorated but statistically changed compared to control. There was a non-significant alteration in the level of CEA in all treated groups compared to normal control one

  5. Hepatoprotective activity of Eugenia jambolana Lam. in carbon tetrachloride treated rats

    Science.gov (United States)

    Sisodia, S.S.; Bhatnagar, M.

    2009-01-01

    Objective: To estimate the hepatoprotective effects of the methanolic seed extract of Eugenia jambolana Lam. (Myrtaceae), in Wistar albino rats treated with carbon tetrachloride (CCl4). Materials and Methods: Liver damage in rats treated with CCl4 (1ml/kg/Bw, administered subcutaneously, on alternate days for one week) was studied by assessing parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), acid phosphatase (ACP) and bilirubin (total and direct). The effect of co-administration of Eugenia jambolana Lam. (doses 100, 200 and 400 mg/kg p. o.) on the above parameters was investigated. These biochemical observations were supplemented by weight and histological examination of liver sections. Liv.52® was used as positive control. Data were analyzed by one way ANOVA, followed by Scheff's/Dunnett's test. Results: Administration of Eugenia jambolana Lam. (doses 100, 200 and 400 mg/kg p. o.) significantly prevented carbon tetrachloride induced elevation of serum SGOT, SGPT, ALP, ACP and bilirubin (total and direct) level. Histological examination of the liver section revealed hepatic regeneration, after administration of various doses of Eugenia jambolana Lam. The results were comparable to that of Liv.52®. Conclusion: The study suggests preventive action of Eugenia jambolana Lam. in carbon tetrachloride induced liver toxicity. Hepatic cell regeneration process was dose dependent. PMID:20177577

  6. Content of carbon monoxide in the tissues of rats intoxicated with carbon monoxide in various conditions of acute exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokal, J.A.; Majka, J.; Palus, J.

    1984-12-01

    Tissue carbon monoxide (CO) content was investigated in rats severely intoxicated with CO under various exposure conditions: 1% CO for 4 min, 0.4% CO for 40 min and 0.12% CO for 12 h. Extravascular CO was determined in the heart and skeletal muscles immediately after termination of exposure, and carboxymyoglobin (MbCO) percent saturation was calculated. Total brain CO was estimated immediately after termination of exposure and after the time periods of restitution. After the same exposure conditions, MbCO percent saturation was higher in the heart than in skeletal muscle. In both types of muscle, saturation on myoglobin (Mb) with CO depended on blood carboxyhemoglobin (HbCO) level and not on the duration of exposure. The time course of CO elimination was the same for blood and brain, irrespective of CO exposure conditions. The results obtained showed that acute CO intoxication induced by long duration exposures did not involve CO accumulation in the tissues.

  7. Olodaterol Oral Inhalation

    Science.gov (United States)

    ... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

  8. Pirbuterol Acetate Oral Inhalation

    Science.gov (United States)

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  9. Cromolyn Oral Inhalation

    Science.gov (United States)

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  10. Ipratropium Oral Inhalation

    Science.gov (United States)

    ... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

  11. Nicotine Oral Inhalation

    Science.gov (United States)

    ... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

  12. Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Bechtold, W.E.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

    1988-01-01

    Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity

  13. Hepatoprotective Potential of Propolis toward Hepar Injury Rats (Rattus norvegicus Induced by Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    Diah Krisnansari

    2016-09-01

    Full Text Available Introduction: The prevalence of chronic liver disease continues to increase. One potentially hepatotoxic substances that cause chronic liver disease is carbon tetrachloride. The process of liver damage can be prevented by the antioxidant role of propolis. The aims of this research was to study the hepatoprotective potential of propolis toward hepar injury rats induced by carbon tetrachlorida. Method: This was an experimental study with pre-post test. Twenty five male Wistar rats aged 12–16 week old, weighing 125–200 gr were allocated into 5 groups. Group I: standard meal + aquadest-gavage; group II: standard meal + CCl4 1% 1 mL + aquadest-gavage, group III: standard meal + CCl4 1% 1 mL + 0,054 gr propolis-gavage, group IV: standard meal + CCl4 1% 1 mL + 0,108 gr propolis-gavage and group V: standard meal + CCl4 1% 1 mL + sylimarin 50 mg/kg-gavage. IL-6, SOD, NAS score+fibrotic were measured after treatment. Analysed of IL-6 and NAS score+fibrotic with Kruskal Wallis to Mann Whitney and analysed of SOD with One-Way ANOVA to LSD. Results: The study showed that there were significant differences in IL-6, SOD and NAS score + fibrotic between groups. Discussion: Provision of 0,054 gr and 0,108 gr have hepatoprotective potential toward hepar injury rats induced by carbon tetrachlorida. Further research need to identify antioxidants and hepatoprotective potential of propolis on human with liver disease. Keywords: IL-6, SOD, fibrotic, propolis

  14. Carbon dioxide in carbonated beverages induces ghrelin release and increased food consumption in male rats: Implications on the onset of obesity.

    Science.gov (United States)

    Eweis, Dureen Samandar; Abed, Fida; Stiban, Johnny

    The dangerous health risks associated with obesity makes it a very serious public health issue. Numerous studies verified a correlation between the increase in obesity and the parallel increase in soft drink consumption among world populations. The effects of one main component in soft drinks namely the carbon dioxide gas has not been studied thoroughly in any previous research. Male rats were subjected to different categories of drinks and evaluated for over a year. Stomach ex vivo experiments were undertaken to evaluate the amount of ghrelin upon different beverage treatments. Moreover, 20 male students were tested for their ghrelin levels after ingestion of different beverages. Here, we show that rats consuming gaseous beverages over a period of around 1 year gain weight at a faster rate than controls on regular degassed carbonated beverage or tap water. This is due to elevated levels of the hunger hormone ghrelin and thus greater food intake in rats drinking carbonated drinks compared to control rats. Moreover, an increase in liver lipid accumulation of rats treated with gaseous drinks is shown opposed to control rats treated with degassed beverage or tap water. In a parallel study, the levels of ghrelin hormone were increased in 20 healthy human males upon drinking carbonated beverages compared to controls. These results implicate a major role for carbon dioxide gas in soft drinks in inducing weight gain and the onset of obesity via ghrelin release and stimulation of the hunger response in male mammals. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  15. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  16. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    International Nuclear Information System (INIS)

    Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

    2014-01-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

  17. Radioactive gas inhalator

    International Nuclear Information System (INIS)

    LeMon, D.E.

    1975-01-01

    An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

  18. Inhalation of diluted diesel engine emission impacts heart rate variability and arrhythmia occurrence in a rat model of chronic ischemic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Anselme, Frederic [Rouen University Hospital, Service de Cardiologie, Rouen (France); Loriot, Stephane; Henry, Jean-Paul; Thuillez, Christian; Morin, Jean-Paul [University of Rouen France, INSERM U644, School of Medicine-Pharmacy, Rouen, Cedex (France); Dionnet, Frederic [Centre d' Etudes et de Recherches Technologiques en Aerothermique et Moteurs, Saint Etienne du Rouvray (France); Napoleoni, Jean-Gerard [EMKA Technologies, Paris (France)

    2007-04-15

    Both increase in cardiac arrhythmia incidence and decrease in heart rate variability (HRV) have been described following human and experimental animal exposures to air pollutants. However, the potential causal relationship between these two factors remains unclear. Incidence of ventricular arrhythmia and HRV were evaluated during and after a 3 h period of Diesel engine exhaust exposure in ten healthy and ten chronic ischemic heart failure (CHF, 3 months after coronary ligation) Wistar rats using implantable ECG telemetry. Air pollutants were delivered to specifically designed whole body individual exposure chambers at particulate matter concentrations similar to those measured inside cabins of cars inserted in congested urban traffic. Recordings were obtained from unrestraint and unsedated vigil rats. Immediate decrease in RMSSD was observed in both healthy (6.64 {+-} 2.62 vs. 4.89 {+-} 1.67 ms, P < 0.05) and CHF rats (8.01 {+-} 0.89 vs. 6.6 {+-} 1.37 ms, P < 0.05) following exposure. An immediate 200-500% increase in ventricular premature beats was observed in CHF rats only. Whereas HRV progressively returned to baseline values within 2.5 h after exposure start, the proarrhythmic effect persisted as late as 5 h after exposure termination in CHF rats. Persistence of ventricular proarrhythmic effects after HRV normalization suggests that HRV reduction is not the mechanism of cardiac arrhythmias in this model. Our methodological approach, closely reflecting the real clinical situations, appeared to be a unique tool to provide further insight into the pathophysiological mechanisms of traffic related airborne pollution health impact. (orig.)

  19. Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats.

    Science.gov (United States)

    El Denshary, Ezzeldeen S; Al-Gahazali, Mohammad A; Mannaa, Fathia A; Salem, Hesham A; Hassan, Nabila S; Abdel-Wahhab, Mosaad A

    2012-11-01

    Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl(4))-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl(4) alone (100 mg/kg b.w) or with CCl(4) after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl(4)-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl(4) induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl(4) plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl(4) after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl(4)-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl(4)-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats.

    Science.gov (United States)

    Junnila, M; Barak, A J; Beckenhauer, H C; Rahko, T

    1998-10-01

    Carbon tetrachloride-injected rats were given liquid diets with and without betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon tetrachloride (CCl4). Animals were killed and their livers and blood taken for analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate aminotransferase. Liver samples were also processed and stained for histological examination. Supplemental betaine reduced triglyceride in the liver and centrilobular hepatic lipidosis induced by the CCl4 injections. In both the control and experimental groups receiving betaine, liver betaine, BHMT and SAM were significantly higher than in their respective groups not receiving betaine. This study provides evidence that betaine protects the liver against CCl4-induced lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating the harmful effects of CCl4.

  1. Inhaling habits among smokers of different types of cigarette

    Energy Technology Data Exchange (ETDEWEB)

    Wald, N.J.; Idle, M.; Boreham, J.; Bailey, A.

    1980-12-01

    Inhaling habits were studied in 1316 men who freely smoked their usual brands of cigarette. An index of inhaling was calculated for each person by dividing the estimated increase in carboxyhaemoglobin level from a standard number of cigarettes by the carbon monoxide yield of the cigarette smoked. Smokers of ventilated filter cigarettes inhaled 82% more than smokers of plain cigarettes (p less than 0.001) and those who smoked unventilated filter cigarettes inhaled 36% more (p less than 0.001). Cigarette consumption was similar among smokers of each type of cigarette. Assuming that the intake of tar and nicotine is proportional to the inhaling index, the intake in either group of filter cigarette smokers would have been less than that in plain cigarette smokers. Among smokers of unventilated cigarettes, however, the intake would not have been much less.

  2. Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

    International Nuclear Information System (INIS)

    Inaji, Motoki; Okauchi, Takashi; Nagai, Yuji; Nojima, Kumie

    2003-01-01

    The present study was designed to make better Parkinson model animal and evaluate the transplantation treatment with ES cell. In the first year, we irradiated left striatum of adult rats with charged carbon particles (290 MeV/nucleon, 5 mm spread-out Bragg peak, 100 Gy) for purpose of making Parkinson model rats. At 4, 8, 12 weeks after the irradiation, we performed the rotation test to methamphetamine and the autoradiography on dopamine D2 receptor and transporter using 11 C-raclopride and 11 C-PE2I to measure the effects of the irradiation. As a result, the number of rotation increased and the distributions of dopamine D2 receptor and transporter in the striatum decreased during the time after the irradiation. These results suggested that the secondary neural damage due to the vascular degeneration caused the progressive destruction of dopamine system. To make more stable Parkinson model rats, we need to use smaller collimator and develop the accurate stereotactic irradiation system in the further research. (author)

  3. Possible Protective Effect of Kombucha Tea Ferment on Carbon Tetrachloride Induced Liver Damage in Irradiated Rats

    International Nuclear Information System (INIS)

    Gharib, O.A.; Fahim, Th.M.

    2008-01-01

    This study has shown that administration of kombucha ferment tea (KT) to rats improved the damage caused in livers of animals treated with toxic chemicals such as carbon tetrachloride (CCL 4 ) and/ or exposed to y-irradiation. This work was undertaken to evaluate the possible protective effects of treatment with KT ferment in rat liver after a long-term treatment with CCL 4 alone and with subsequent y-irradiation. Hepatic pathological changes observed in the CCL 4 -treated rats included increased serum alanine transaminase (ALT) , aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities as well as concentration of bilirubin in addition to a decrease in the concentration of serum albumin and total antioxidant capacity (TAC). Consistent with these changes, the increase in oxidative stress markers expressed as malondialdehyde (MDA) concentration and depletion in glutathione (GSH) contents in liver was observed. 24 h after the last dose of KT administration in a group of animals treated with CCL 4 and/ or radiation exposure cessation, the pathological changes were recovered. These results demonstrate that most of the pathological alterations in the liver in response to CCL 4 and/ or radiation exposure intoxication are recoverable upon treatment with KT ferments

  4. The protective role of pomegranate juice against carbon tetrachloride-induced oxidative stress in rats.

    Science.gov (United States)

    Pirinççioğlu, Mihdiye; Kızıl, Göksel; Kızıl, Murat; Kanay, Zeki; Ketani, Aydın

    2014-11-01

    Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl4)-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4 was administered once a week to groups II, III and IV during the experimental period. CCl4-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl4 along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl4-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity. © The Author(s) 2012.

  5. Effects of carbonated soft drink consumption on orthodontic tooth movements in rats.

    Directory of Open Access Journals (Sweden)

    Hossein Agha Aghili

    2014-04-01

    Full Text Available The aim of this animal study was to evaluate the possible effects of Carbonated Soft Drink consumption on the rate of orthodontic tooth movement in rats.Thirty-six adult male Sprague-Dawley rats were randomly divided into two experimental groups and one control group. In the experimental groups (A&B, the water in the dietary regimen was replaced with soft drinks (Fanta® in group A and Cola® in group B two weeks before placement of orthodontic appliances. Then 5-mm nickel-titanium closed-coil springs were placed between the maxillary right first molars and first incisors under general anesthesia. This regimen continued for two weeks more and animals drank soft drink ad libitum. At the end of the experimental period, the rats were sacrificed, and interproximal tooth movements were measured.The mean amounts of tooth movement were 0.19mm in group A, 0.22mm in group B and 0.37mm in group C. Statistical analysis with analysis of variance (ANOVA test showed significant differences between all groups. The least movement occurred in group A that had received Fanta® drink.CSDs consumption decreases the rate of orthodontic tooth movement. The role of soft drinks in decreasing tooth movement might be related to its effects on bone metabolism.

  6. Fermented Citrus Lemon Reduces Liver Injury Induced by Carbon Tetrachloride in Rats

    Directory of Open Access Journals (Sweden)

    Yi Jinn Lillian Chen

    2018-01-01

    Full Text Available Fermented lemon juice displays a variety of important biological activities, including anti-inflammatory and antioxidant capabilities. The aim of the present study is to investigate hepatic-protective effects of no-sugar-added fermented lemon juice (FLJ for liver inflammation caused by carbon tetrachloride (CCl4 in rats. Rats are divided into six groups: H2O, CCl4 + H2O, CCl4 + silymarin, and CCl4 plus three different FLJ doses by oral administration, respectively. The results show that the contents of plasma ALT and AST, hepatic lipid peroxidation, splenomegaly, and liver water are reduced significantly in rats under FLJ treatment, and pathological examination of liver fibrosis is improved. The reduced hepatic injury by increasing liver soluble protein and glutathione and albumin is observed in FLJ treated groups, and FLJ has comparable efficacies to medicine silymarin in liver therapies. The no-sugar-added FLJ differs from traditional fermentation by adding lots of sugar and prevents any hidden sugar intake while taking it as a complimentary treatment for liver inflammation. The green color and the taste of sourness are both associated with treating and healing the liver based on the five-element theory in traditional Chinese medicine, and the green and sour FLJ may be applied to the ancient theory in preventing hepatic injury accordingly.

  7. Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats.

    Science.gov (United States)

    Kania, Nia; Setiawan, Bambang; Widjadjanto, Edi; Nurdiana, Nurdiana; Widodo, M Aris; Kusuma, H M S Chandra

    2014-10-01

    Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM10 coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p>0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p>0.05), but there was a significant difference in MUC5AC expression (phyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. A SUBCHRONIC INHALATION STUDY OF FISCHER 344 RATS EXPOSED TO 0, 0.4, 1.4 OR 4.0 PPM ACROLEIN

    International Nuclear Information System (INIS)

    KUTZMAN, R.S.

    1981-01-01

    Fischer 344 rats were exposed to 0.0, 0.4, 1.4, or 4.0 ppm acrolein for 62 days. The major objective of the study was to relate the results of a series of pulmonary function tests to biochemical and pathological alterations observed in the lung. Cytological and reproductive potential endpoints were also assessed after acrolein exposure. Rats were exposed to acrolein for 6 hours/day, 5 days/week for 62 days. Mortality was observed only in the 4.0 ppm chamber where 32 of 57 exposed males died; however, none of the 8 exposed females died. Most of the mortality occurred within the first 10 exposure days. Histologic examination indicated that the animals died of acute bronchopneumonia. The surviving males and females exposed to 4.0 ppm acrolein gained weight at a significantly slower rate than control animals. The growth of both sexes in the 0.4 and 1.4 ppm groups was similar to that of their respective controls. Histopathologic examination of animals after 62 days of exposure revealed bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema in the 4.0 ppm group. These lesions were, in some cases, associated with edema of the trachea and peribronchial lymph nodes, and acute rhinitis which indicated an upper respiratory tract effect of acrolein. Of particular interest was the variability of response between rats in the 4.0 ppm group, some not affected at all while others were moderately affected. Intragroup variability in toxicity was also apparent in the 1.4 ppm exposure group where only 3 of 31 animals examined had lesions directly related to acrolein exposure. Extra respiratory organs appeared unaffected

  9. Respiratory irritation associated with inhalation of boron trifluoride and fluorosulfonic acid

    NARCIS (Netherlands)

    Rusch, G.M.; Bowden, A.M.; Muijser, H.; Arts, J.

    2008-01-01

    The objectives of this study were to examine the respiratory irritancy of boron trifluoride (BF3) and fluorosulfonic acid (FSA) following acute inhalation exposure. Testing was conducted using groups of 10 male and 10 female rats (BF3) or groups of 6 male rats (FSA). Rats were exposed for a single

  10. Inhaled americium dioxide

    International Nuclear Information System (INIS)

    Park, J.F.

    1982-01-01

    This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

  11. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

  12. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure

    Directory of Open Access Journals (Sweden)

    Olivier Phan

    2015-01-01

    Full Text Available Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23 levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21, a new iron-based phosphate binder, versus lanthanum carbonate (La and sevelamer carbonate (Se, on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

  13. Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats.

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    Jingyan Liang

    Full Text Available Hot spring or hot spa bathing (Onsen is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

  14. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

    Science.gov (United States)

    Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Hossain, Hemayet; Alam, Md Ashraful

    2015-01-01

    Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  15. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4 Treated Rats

    Directory of Open Access Journals (Sweden)

    Mohammed Riaz Hasan Chowdhury

    2015-01-01

    Full Text Available Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (−-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4 treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA, nitric oxide, advanced protein oxidation products level (APOP, and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  16. Cobalamin Deficiency Results in Increased Production of Formate Secondary to Decreased Mitochondrial Oxidation of One-Carbon Units in Rats.

    Science.gov (United States)

    MacMillan, Luke; Tingley, Garrett; Young, Sara K; Clow, Kathy A; Randell, Edward W; Brosnan, Margaret E; Brosnan, John T

    2018-03-01

    Formate is produced in mitochondria via the catabolism of serine, glycine, dimethylglycine, and sarcosine. Formate produced by mitochondria may be incorporated into the cytosolic folate pool where it can be used for important biosynthetic reactions. Previous studies from our lab have shown that cobalamin deficiency results in increased plasma formate concentrations. Our goal was to determine the basis for elevated formate in vitamin B-12 deficiency. Male Sprague Dawley rats were randomly assigned to consume either a cobalamin-replete (50 μg cobalamin/kg diet) or -deficient (no added cobalamin) diet for 6 wk. Formate production was measured in vivo and in isolated liver mitochondria from a variety of one-carbon precursors. We also measured the oxidation of [3-14C]-l-serine to 14CO2 in isolated rat liver mitochondria and the expression of hepatic genes involved in one-carbon unit and formate metabolism. Cobalamin-deficient rats produce formate at a rate 55% higher than that of replete rats. Formate production from serine was increased by 60% and from dimethylglycine and sarcosine by ∼200% in liver mitochondria isolated from cobalamin-deficient rats compared with cobalamin-replete rats. There was a 26% decrease in the 14CO2 produced by mitochondria from cobalamin-deficient rats. Gene expression analysis showed that 10-formyltetrahydrofolate dehydrogenase-cytosolic (Aldh1l1) and mitochondrial (Aldh1l2) expression were decreased by 40% and 60%, respectively, compared to control, while 10-formyltetrahydrofolate synthetase, mitochondrial, monofunctional (Mthfd1l) expression was unchanged. We propose that a bifurcation in mitochondrial one-carbon metabolism is a key control mechanism in determining the fate of one-carbon units, to formate or CO2. During cobalamin deficiency in rats the disposition of 10-formyl-tetrahydrofolate carbon is shifted in favor of formate production. This may represent a mechanism to generate more one-carbon units for the replenishment of the S

  17. Acute toxicity of the hydrolysis products of uranium hexafluoride (UF6) when inhaled by the rat and guinea pig. Final report

    International Nuclear Information System (INIS)

    Leach, L.J.; Gelein, R.M.; Panner, B.J.; Yulie, C.L.; Cox, C.C.; Balys, M.M.; Rolchigo, P.M.

    1984-04-01

    This report presents the experimental animal data base from which human health consequences may be predicted from exposures mimicing accidental discharges of uranium hexafluoride (UF 6 ) in the uranium industry. Rats or guinea pigs were exposed for two, five, or ten minutes duration to air having 0.44 g U/m 3 + 0.16 g HF/m 3 to 276.67 g U/m 3 + 94.07 g HF/m 3 . Survivors of each exposure were observed for 14 days for signs of U or HF intoxication. Selected animals were necropsied and samples of major organs were studied histopathologically. When enriched UF 6 (94 percent 235 U) was used, the urine and feces from each animal were measured daily for U content. Selected samples of urine were bioassayed in order to trace the course of renal injury during the two week postexposure period. 28 references, 51 figures, 23 tables

  18. H,K-ATPase and carbonic anhydrase response to chronic systemic rat gastric hypoxia

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    Ulfah Lutfiah

    2015-11-01

    Full Text Available Background: Hypoxia may induce gastric ulcer associated with excessive hidrogen chloride (HCl secretion. Synthesis of HCl involves 2 enzymes, H,K-ATPase and carbonic anhydrase (CA. This study aimed to clarify the underlying cause of gastric ulcer in chronic hypoxic condition, by investigating the H,K-ATPase and CA9 response in rats.Methods: This study was an in vivo experiment, to know the relationship between hypoxia to expression of H,K-ATPase and CA9 mRNA, and H,K-ATPase and total CA specific activity of chronic systemic rat gastric hypoxia. The result was compared to control. Data was analyzed by SPSS. If the data distribution was normal and homogeneous, ANOVA and LSD post-hoc test were used. However, if the distribution was not normal and not homogeneous, and still as such after transformation, data was treated in non-parametric using Kruskal-Wallis and Mann Whitney test. Twenty five male Sprague-Dawley rats were divided into 5 groups: rats undergoing hypoxia for 1, 3, 5, and 7 days placed in hypoxia chamber (10% O2, 90% N2, and one control group. Following this treatment, stomach of the rats was extracted and homogenized. Expression of H,K-ATPase and CA9 mRNA was measured using real time RT-PCR. Specific activity of H,K-ATPase was measured using phosphate standard solution, and specific activity of total CA was measured using p-nitrophenol solution.Results: The expression of H,K-ATPase mRNA was higher in the first day (2.159, and drastically lowered from the third to seventh day (0.289; 0.108; 0.062. Specific activities of H,K-ATPase was slightly higher in the first day (0.765, then was lowered in the third (0.685 and fifth day (0.655, and was higher in the seventh day (0.884. The expression of CA9 mRNA was lowered progressively from the first to seventh day (0.84; 0.766; 0.736; 0.343. Specific activities of total CA was low in the first day (0.083, and was higher from the third to seventh day (0.111; 0.136; 0.144.Conclusion: In hypoxia

  19. RNA sequencing analysis reveals new findings of hyperbaric oxygen treatment on rats with acute carbon monoxide poisoning.

    Science.gov (United States)

    Wang, Wenlan; Xue, Li; Li, Ya; Li, Rong; Xie, Xiaoping; Bao, Junxiang; Hai, Chunxu; Li, Jinsheng

    2016-01-01

    To elucidate the altered gene network in the brains of carbon monoxide (CO) poisoned rats after treatment with hyperbaric oxygen (HBO₂). RNA sequencing (RNA-seq) analysis was performed to examine differentially expressed genes (DEGs) in brain tissue samples from nine male rats: a normal control group; a CO poisoning group; and an HBO₂ treatment group (three rats/group). Reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR were used for validation of the DEGs in another 18 male rats (six rats/group). RNA-seq revealed that two genes were upregulated (4.18 and 8.76 log to the base 2 fold change) (p⟨0.05) in the CO-poisoned rats relative to the control rats; two genes were upregulated (3.88 and 7.69 log to the base 2 fold change); and 23 genes were downregulated (3.49-15.12 log to the base 2 fold change) (p⟨0.05) in the brains of the HBO₂-treated rats relative to the CO-poisoned rats. Target prediction of DEGs by gene network analysis and analysis of pathways affected suggested that regulation of gene expressions of dopamine metabolism and nitric oxide (NO) synthesis were significantly affected by CO poisoning and HBO₂ treatment. Results of RT-PCR and real-time quantitative PCR indicated that four genes (Pomc, GH-1, Pr1 and Fshβ) associated with hormone secretion in the hypothalamic-pituitary system have potential as markers for prognosis of CO. This study is the first RNA-seq analysis profile of HBO₂ treatment on rats with acute CO poisoning. It concludes that changes of hormone secretion in the hypothalamic-pituitary system, dopamine metabolism and NO synthesis involved in brain damage and behavior abnormalities after CO poisoning and HBO₂ therapy may regulate these changes.

  20. the reproductive dysfunction effects of gasoline inhalation in albino

    African Journals Online (AJOL)

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    exposure to inhalation gasoline, which generally saturate the ambient air of their workplaces. In this study, we challenged male and female albino rats with gasoline vapour and monitored the endocrine disruptive effects as part of a comprehensive study of the health risks faced by refinery workers in Nigeria. The ultimate.

  1. Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

    2008-01-01

    To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (pliver disease are warranted.

  2. Nephroprotective effects of Colpomenia sinuosa (Derbes & Solier against carbon tetrachloride induced kidney injury in Wistar rats

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    Lekameera Ramarajan

    2012-05-01

    Full Text Available Objective: To establish the protective effect of seaweed Colpomenia sinuosa against carbon tetra chloride (CCl4 induced oxidative stress and resultant dysfunction of rat kidney. Methods: Seven to eight weeks old male Wistar rats (150-220g were exposed to CCl4 (1.5 ml/kg injection then treated with seaweed Colpomenia sinuosa (100 mg/kg body weight in 0.3% CMC solution. Blood was collected at the 5th day of experimental period to estimate the Total count (TC, Hemoglobin (HB, Total protein (TP, Glucose, Albumin, Cholesterol, TGL and Urea. Results: The results shows significantly decreased (P<0.01 level of TC, the cholesterol and urea levels shows significantly increased (P<0.05 in CCl4 treated groups when compared to control groups. These levels were found to be normalized by oral feeding of C. sinuosa. Then the rats were sacrificed and kidneys taken for enzyme analyses and histological examination. In the CCl4 treated group significantly increased activities in TBARS, SOD, CAT, GPX, GSH (P<0.05 when compared to control group. These increased activities were found to near normal in the CCl 4 + C. sinuosa treated group and Seaweed C. sinuosa treated alone group did not change any enzyme activity. Exposure to CCl4 resulted hydrobhic changes in epithelium and Hypercellulartity of glomerulus was seen in the CCl 4 + drug treated group. Conclusions: These results suggest that the nephroprotective effect of C. sinuosa can be attributed to its enhancing effects on antioxidant defense system and lead to prevent the damage by exposure of CCl4 toxicity.

  3. Determination of puerarin in rat plasma using PEGylated magnetic carbon nanotubes by high performance liquid chromatography.

    Science.gov (United States)

    Yu, Panfeng; Wang, Qi; Ma, Hongwei; Wu, Ji; Shen, Shun

    2014-05-15

    This paper described a novel application of PEGylated magnetic carbon nanotubes as solid-phase extraction nanosorbents for the determination of puerarin in rat plasma by high performance liquid chromatography (HPLC). A solvothermal method was employed for the synthesis of monodisperse magnetites anchored onto multi-walled carbon nanotubes (MWCNTs@Fe3O4). In order to enhance the water solubility of MWCNTs@Fe3O4 that ensured sufficient contact between nanosorbents and analytes in the sampling procedure, the obtained nanomaterials were further noncovalently functionalized using a phospholipids-polyethylene glycol (DSPE-PEG). The PEGylated MWCNTs@Fe3O4 nanomaterials had an extremely large surface area and exhibit a strong interaction capability for puerarin with π-π stacking interactions. The captured puerarin/nanosorbents were easily isolated from the plasma by placing a magnet, and desorbed by acetonitrile. The experimental variables affecting the extraction efficiency were investigated. The calibration curve of puerarin was linear from 0.01 to 20 μg/ml, and the limit of detection was 0.005 μg/ml. The precisions ranged from 2.7% to 3.5% for within-day measurement, and for between-day variation was in the range of 3.1-5.9%. The method recoveries were acquired from 95.2% to 98.0%. Moreover, the analytical performance obtained by PEGylated magnetic MWCNTs was also compared with that of magnetic MWCNTs. All results showed that our proposed method was an excellent alternative for the analysis of puerarin in rat plasma. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Protective Effect of Edaravone against Carbon Monoxide Induced Apoptosis in Rat Primary Cultured Astrocytes

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    Xiaodan Xu

    2017-01-01

    Full Text Available Objective. To observe the protective effect of edaravone (Eda on astrocytes after prolonged exposure to carbon monoxide (CO and further to investigate the potential mechanisms of Eda against CO-induced apoptosis. Methods. The rat primary cultured astrocytes were cultured in vitro and exposed to 1% CO for 24 h after being cultured with different concentrations of Eda. MTT assay was used to detect the cytotoxicity of CO. Flow cytometry was used to detect the apoptosis rate, membrane potential of mitochondria, and ROS level. The mRNA and protein expressions of Bcl-2, Bax, and caspase-3 were assessed by real-time PCR and Western blotting analysis, respectively. Results. Eda can significantly suppress cytotoxicity of CO, and it can significantly increase membrane potential of mitochondria and Bcl-2 expressions and significantly suppress the apoptosis rate, ROS level, Bax, and caspase-3 expressions. Conclusion. Eda protects against CO-induced apoptosis in rat primary cultured astrocytes through decreasing ROS production and subsequently inhibiting mitochondrial apoptosis pathway.

  5. Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets.

    Science.gov (United States)

    Sá, M A; Andrade, V B; Mendes, R M; Caliari, M V; Ladeira, L O; Silva, E E; Silva, G A B; Corrêa-Júnior, J D; Ferreira, A J

    2013-07-01

    We evaluated the effects of sodium hyaluronate (HY) and carbon nanotubes functionalized with HY (HY-CNT) on bone repair in the tooth sockets of diabetic rats. Diabetes was induced by streptozotocin (50 mg kg(-1) i.v.), and the sockets were divided into normal control, diabetic control, diabetic treated with HY (1%), and diabetic treated with HY-CNT (100 μg ml(-1)) groups. The sockets were analyzed according to the percentage of bone formation and the number of cell nuclei. The percentage of bone trabeculae was lower in diabetic control animals (11.16 ± 5.10% vs 41.92 ± 6.34% in normal animals) after 14 days. Treating diabetic animals with HY or HY-CNT significantly increased the percentage of neoformed trabeculae (HY: 29.43 ± 3.29%; HY-CNT: 36.90 ± 3.07%). Moreover, the sockets of diabetic animals had an increased number of cell nuclei and HY or HY-CNT reduced this parameter. Our results indicate that HY and HY-CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

    Science.gov (United States)

    Young, Shun-Chieh; Wang, Chau-Jong; Lin, Jing-Jing; Peng, Pei-Ling; Hsu, Jui-Ling; Chou, Fen-Pi

    2007-01-01

    Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

  7. Histological and elemental changes in the rat brain after local irradiation with carbon ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Sentaro; Sun, Xue-Zhi; Kubota, Yoshihisa; Takai, Nobuhiko; Nojima, Kumie [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-06-01

    The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated at doses of 30, 50, or 100 Gy with charged carbon particles (290 MeV/nucleon; 5 mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. A histological examination showed that necrotic tissue damage, hemorrhage in the thalamus, and vasodilatations around the necrotic region were induced at 8 weeks after 100 Gy irradiation. The regions with tissue damage correlated well with those expected from the radiation-dose distribution, indicating an advantage of charged carbon particles for irradiating restricted brain regions. An X-ray fluorescent analysis demonstrated a decrease in the concentrations of K and P, and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8 weeks post-irradiation, though no significant changes were observed before 4 weeks of post-irradiation. This may indicate that even the very high radiation doses used here did not induce acute and immediate neuronal cell death, in contrast with ischemic brain injury where acute neuronal cell death occurred and the elemental concentrations changed within a day after the induction of ischemia. (author)

  8. Protective effects of Lactuca sativa ethanolic extract on carbon tetrachloride induced oxidative damage in rats

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    Hefnawy Taha M. Hefnawy

    2013-08-01

    Full Text Available Objective: To study the protective effects of the ethanolic extract of lettuce (Lactuca sativa L. var. longifolia leaves against the toxicity caused by carbon tetrachloride (CCl4 in reproductive system of rats. Methods: Lettuce leaves were dried and extracted with ethanol (plant: solvent, 1:10, w/v. The extract was filtered and evaporated to yield dried lettuce extract. Animals were divided into seven groups and treated with CCl4 and different concentrations of lettuce extract. At the end of the experimental period, the animals were sacrificed and blood was collected and centrifuged for serum separation. Body weights, testis size, histopathology of testis and liver, catalase (CAT activity, superoxide dismutase (SOD activity, peroxidase (POD activity, reduced glutathione (GSH, glutathione peroxidase activity (GSH-Px, thiobarbituric acid reactive substances (TBARS, nitrite level, and serum hormones were determined. Results: Oxidative stress induced by CCl4 (2 mL/kg body weight in rat decreases the increase in body weight and relative testis weight. It also markedly increases the level of TBARS and nitrites along with corresponding decrease in reduced glutathione and various antioxidant enzymes in testis (i.e., CAT, POD, SOD and GSH-Px. Serum level of testosterone, luteinizing hormone and follicle stimulating hormone was decreased while estradiol and prolactin were increased during CCl 4 treatment. Histopathology of CCl4-treated rats indicated the partial degeneration of germ and leydig cells along with deformities in spermatogenesis. Supplementation of lettuce extract (100, 150, 200 mg/kg body weight orally once a week for 10 weeks results in decrease of TBARS and nitrite, while increase in antioxidant enzymes; CAT, POD, SOD, GSH-Px and GSH contents. Serum level of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, histology, body weight and relative testis weight was also concomitantly restored to near normal

  9. Protective effects of Lactuca sativa ethanolic extract on carbon tetrachloride induced oxidative damage in rats

    Science.gov (United States)

    Hefnawy, Hefnawy Taha M.; Ramadan, Mohamed Fawzy

    2013-01-01

    Objective To study the protective effects of the ethanolic extract of lettuce (Lactuca sativa L. var. longifolia) leaves against the toxicity caused by carbon tetrachloride (CCl4) in reproductive system of rats. Methods Lettuce leaves were dried and extracted with ethanol (plant: solvent, 1:10, w/v). The extract was filtered and evaporated to yield dried lettuce extract. Animals were divided into seven groups and treated with CCl4 and different concentrations of lettuce extract. At the end of the experimental period, the animals were sacrificed and blood was collected and centrifuged for serum separation. Body weights, testis size, histopathology of testis and liver, catalase (CAT) activity, superoxide dismutase (SOD) activity, peroxidase (POD) activity, reduced glutathione (GSH), glutathione peroxidase activity (GSH-Px), thiobarbituric acid reactive substances (TBARS), nitrite level, and serum hormones were determined. Results Oxidative stress induced by CCl4 (2 mL/kg body weight) in rat decreases the increase in body weight and relative testis weight. It also markedly increases the level of TBARS and nitrites along with corresponding decrease in reduced glutathione and various antioxidant enzymes in testis (i.e., CAT, POD, SOD and GSH-Px). Serum level of testosterone, luteinizing hormone and follicle stimulating hormone was decreased while estradiol and prolactin were increased during CCl4 treatment. Histopathology of CCl4-treated rats indicated the partial degeneration of germ and leydig cells along with deformities in spermatogenesis. Supplementation of lettuce extract (100, 150, 200 mg/kg body weight orally) once a week for 10 weeks results in decrease of TBARS and nitrite, while increase in antioxidant enzymes; CAT, POD, SOD, GSH-Px and GSH contents. Serum level of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, histology, body weight and relative testis weight was also concomitantly restored to near normal level by

  10. Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

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    Tongtong Zhang

    2018-05-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency. Key words: Curcumin, Dry powder inhaler, Liposome, Primary lung cancer, Pulmonary delivery

  11. Effects of carbon dioxide therapy on the healing of acute skin wounds induced on the back of rats

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    Maria Vitória Carmo Penhavel

    2013-05-01

    Full Text Available PURPOSE: To evaluate the healing effect of carbon dioxide therapy on skin wounds induced on the back of rats. METHODS: Sixteen rats underwent excision of a round dermal-epidermal dorsal skin flap of 2.5 cm in diameter. The animals were divided into two groups, as follows: carbon dioxide group - subcutaneous injections of carbon dioxide on the day of operation and at three, six and nine days postoperatively; control group - no postoperative wound treatment. Wounds were photographed on the day of operation and at six and 14 days postoperatively for analysis of wound area and major diameter. All animals were euthanized on day 14 after surgery. The dorsal skin and the underlying muscle layer containing the wound were resected for histopathological analysis. RESULTS: There was no statistically significant difference between groups in the percentage of wound closure, in histopathological findings, or in the reduction of wound area and major diameter at 14 days postoperatively. CONCLUSION: Under the experimental conditions in which this study was conducted, carbon dioxide therapy had no effects on the healing of acute skin wounds in rats.

  12. Food hypersensitivity by inhalation

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    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  13. Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

    Science.gov (United States)

    Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

    2003-02-01

    Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the

  14. Inhaled transuranics in rodents

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1983-01-01

    This project examines the interactions of external and internal radiation from mixtures of radionuclides present within the nuclear fuel inventory. The objective of the project is to evaluate the effects of mixed radiation insults, using key radiation sources as indicative of overall processes that may occur following release of nuclear fuel into the air. Previously initiated studies of immunological effects of plutonium inhalation are also being completed as part of this project

  15. Experimental study of the combined effects of inhalation of radon daughter products and tobacco smoke

    International Nuclear Information System (INIS)

    Chameaud, J.; Perraud, R.; Chretien, J.; Masse, R.; Lafuma, J.

    1979-01-01

    For 10 years, over 500 lung cancers have been induced in rats by inhalations of radon daughter products at various concentrations and cumulated doses. Considering several points and the dose-effect relationship especially, such cancers can be compared with human cancers. This type of experiments, fully mastered, has made it possible to undertake under good conditions the study of the co-carcinogenic effect of various inhaled pollutants such as tobacco smoke. In a first experiment, 100 rats were exposed to a 4000WLM cumulated dose of radon daughter products, knowing that this level induces some 30% of lung cancers. 50 animals were then administered tobacco smoke by inhalation in a fume box during 5 months (350 h.) In the group inhaling radon only, 17 cancers appeared; in the radon -tobacco group 32 cancers bigger and more invasive were observed. Under the same conditions, tobacco smoke was inhaled by rats previously exposed to lower doses of radon daughter products (2 groups of 30 rats, 500 and 100 WLM respectively). Again, the number of cancers observed was higher that the number of cancers expected if the rats had inhaled radon only. This co-carcinogenic and potentiating action of tobacco was clearly demonstrated. Further experiments are considered in order to determine the processes involved

  16. Characteristic pathological changes of main organs of rates after inhalation of depleted uranium aerosol

    International Nuclear Information System (INIS)

    Cao Zhenshan; Zhu Maoxiang; Yang Zhihua; Pan Xiujie; Li Yuanmin

    2005-01-01

    Objective: To explore the pathological and morphometric alteration of main organs of rat after inhalation of depleted uranium (DU) aerosole in order to provide information for medical protection against DU weapons. Methods: Routine pathological technique and morphometric measurements were used to observe histopathological and morphological changes in lung, kidney, spleen, liver, brain of rats 1-14 months after inhalation of DU aerosol. Results: After inhalation of DU aerosol, lymphocytic infiltration in the pulmonary parenchyma, serious bronchitis, pulmonary hemorrhage and abscess formation were seen in some of the rats; distinct dilatation of tubules in renal cortex and papillae, casts in some tubules of the cortex, medulla and papillae, and interstitial hemorrhage were found in some other rats; diminution of the area of splenic white pulp, reduction of megakaryocytic mitosis were also observed, the incidence and severity of above changes in the lung and kidney, but not in the liver and brain, showed dependance on the length of time after inhalation or the dose of DU inhaled. Conclusion There are evident injurious effects on rat lung, kidney and spleen by inhalation of DU aerosol. (authors)

  17. High Antifouling Property of Ion-Selective Membrane: toward In Vivo Monitoring of pH Change in Live Brain of Rats with Membrane-Coated Carbon Fiber Electrodes.

    Science.gov (United States)

    Hao, Jie; Xiao, Tongfang; Wu, Fei; Yu, Ping; Mao, Lanqun

    2016-11-15

    In vivo monitoring of pH in live brain remains very essential to understanding acid-base chemistry in various physiological processes. This study demonstrates a potentiometric method for in vivo monitoring of pH in the central nervous system with carbon fiber-based proton-selective electrodes (CF-H + ISEs) with high antifouling property. The CF-H + ISEs are prepared by formation of a H + -selective membrane (H + ISM) with polyvinyl chloride polymeric matrixes containing plasticizer bis(2-ethylhexyl)sebacate, H + ionophore tridodecylamine, and ion exchanger potassium tetrakis(4-chlorophenyl)borate onto carbon fiber electrodes (CFEs). Both in vitro and in vivo studies demonstrate that the H + ISM exhibits strong antifouling property against proteins, which enables the CF-H + ISEs to well maintain the sensitivity and reversibility for pH sensing after in vivo measurements. Moreover, the CF-H + ISEs exhibit a good response to pH changes within a narrow physiological pH range from 6.0 to 8.0 in quick response time with high reversibility and selectivity against species endogenously existing in the central nervous system. The applicability of the CF-H + ISEs is illustrated by real-time monitoring of pH changes during acid-base disturbances, in which the brain acidosis is induced by CO 2 inhalation and brain alkalosis is induced by bicarbonate injections. The results demonstrate that brain pH value rapidly decreases in the amygdaloid nucleus by ca. 0.14 ± 0.01 (n = 5) when the rats breath in pure CO 2 gas, while increases in the cortex by about 0.77 ± 0.12 (n = 3) following intraperitoneal injection of 5 mmol/kg NaHCO 3 . This study demonstrates a new potentiometric method for in vivo measurement of pH change in the live brain of rats with high reliability.

  18. Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?

    Science.gov (United States)

    Van der Meeren, Anne; Moureau, Agnes; Griffiths, Nina M

    2014-11-01

    Abstract Purpose: To investigate the consequences of alveolar macrophage (AM) depletion on Mixed OXide fuel (MOX: U, Pu oxide) distribution and clearance, as well as lung damage following MOX inhalation. Rats were exposed to MOX by nose only inhalation. AM were depleted with intratracheal administration of liposomal clodronate at 6 weeks. Lung changes, macrophage activation, as well as local and systemic actinide distribution were studied up to 3 months post-inhalation. Clodronate administration modified excretion/retention patterns of α activity. At 3 months post-inhalation lung retention was higher in clodronate-treated rats compared to Phosphate Buffered Saline (PBS)-treated rats, and AM-associated α activity was also increased. Retention in liver was higher in clodronate-treated rats and fecal and urinary excretions were lower. Three months after inhalation, rats exhibited lung fibrotic lesions and alveolitis, with no marked differences between the two groups. Foamy macrophages of M2 subtype [inducible Nitric Oxide Synthase (iNOS) negative but galectin-3 positive] were frequently observed, in correlation with the accumulation of MOX particles. AM from all MOX-exposed rats showed increased chemokine levels as compared to sham controls. Despite the transient reduced AM numbers in clodronate-treated animals no major differences on lung damage were observed as compared to non-treated rats after MOX inhalation. The higher lung activity retention in rats receiving clodronate seems to be part of a general inflammatory response and needs further investigation.

  19. Effect of fasting and different diets on 14C incorporation from U-14C glucose into glycogen and carbon dioxide by cerebral cortical slices of rats

    International Nuclear Information System (INIS)

    Visweswaran, P.; Binod Kumar; Sinha, A.P.; Suraiya, A.; Brahamchari, A.K.; Singh, S.P.

    1994-01-01

    There are some reports regarding change in the glycogen level due to fasting. Here an attempt is made by keeping the albino rats under fasting or feeding different diets on the rate of 14 C incorporation into glycogen and carbon dioxide from U- 14 C glucose. Our study reveals that the above conditions do not alter any significant change in the glycogen and carbon dioxide in the cerebral cortical slices of albino rats. (author). 8 refs., 1 tab

  20. DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    Science.gov (United States)

    Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

  1. DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    Science.gov (United States)

    Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

  2. Metabolism and disposition of ethylene carbonate in male Fischer 344 rats

    International Nuclear Information System (INIS)

    Hanley, T.R. Jr.; Schumann, A.M.; Langvardt, P.W.; Rusek, T.F.; Watanabe, P.G.

    1989-01-01

    Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [ 14 C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as 14CO2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of 13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [ 14 C]EG (141 mg/kg), approximately 37% of the dose was expired as 14 CO 2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified

  3. Incorporation of 14C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

    International Nuclear Information System (INIS)

    Sikorska, M.; Gorzkowski, B.; Szumanska, G.; Smialek, M.

    1975-01-01

    Incorporation of 14 C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value. (Z.M.)

  4. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

    Science.gov (United States)

    El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

    2016-04-01

    In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

  5. The influence of cigarette smoke inhalation on bone density: a radiographic study in rats Influência da fumaça de cigarro na densidade óssea: estudo radiográfico em ratos

    Directory of Open Access Journals (Sweden)

    João Batista César-Neto

    2005-03-01

    Full Text Available The aim of this study was to evaluate the influence of cigarette smoke inhalation (CSI and its cessation on tibiae bone quality. Forty-one male Wistar rats were randomly assigned to one of the following groups: Group 1 - control (n = 14, Group 2 - 3 months of CSI and 2 months without exposure to CSI (n = 12, and Group 3 - 5 months of CSI (n = 15. At the end of the experimental period, the animals were sacrificed, the tibiae removed and immediately radiographed for photodensitometric analysis. The results showed that continuous exposure to cigarette smoke promoted a significantly reduced bone density (p 0.05. Thus, within the limits of the present study, it can be concluded that CSI may affect tibiae bone quality, and CSI cessation results in a return towards the level of the control group.O objetivo deste estudo foi avaliar a influência da inalação da fumaça de cigarro (IFC e o efeito de sua interrupção na qualidade óssea da tíbia. Quarenta e um ratos Wistar machos foram aleatoriamente designados a um dos seguintes grupos: Grupo 1 - controle (n = 14, Grupo 2 - 3 meses de IFC e 2 meses sem exposição à fumaça (n = 12 e Grupo 3 - 5 meses de IFC (n = 15. Ao final do período experimental, os animais foram sacrificados, as tíbias removidas e imediatamente radiografadas para a análise fotodensitométrica. Os resultados mostraram que a exposição contínua à fumaça de cigarro promoveu uma significante redução na densidade óssea (p 0,05. Portanto, dentro dos limites do presente estudo, pode-se concluir que a IFC pode influenciar a qualidade óssea da tíbia e que a interrupção da inalação parece reverter esse efeito negativo resultando numa densidade óssea semelhante à do grupo controle.

  6. Emergency department management of smoke inhalation injury in adults [digest].

    Science.gov (United States)

    Otterness, Karalynn; Ahn, Christine; Nusbaum, Jeffrey; Gupta, Nachi

    2018-03-01

    Smoke inhalation injury portends increased morbidity and mortality in fire-exposed patients. Upper airway thermal burns, inflammation from lower airway irritants, and systemic effects of carbon monoxide and cyanide can contribute to injury. A standardized diagnostic protocol for inhalation injury is lacking, and management remains mostly supportive. Clinicians should maintain a high index of suspicion for concomitant traumatic injuries. Diagnosis is mostly clinical, aided by bronchoscopy and other supplementary tests. Treatment includes airway and respiratory support, lung protective ventilation, 100% oxygen or hyperbaric oxygen therapy for carbon monoxide poisoning, and hydroxocobalamin for cyanide toxicity. Due to its progressive nature, many patients with smoke inhalation injury warrant close monitoring for development of airway compromise. [Points & Pearls is a digest of Emergency Medicine Practice.].

  7. Hepatoprotective Effect of Trigona spp. Bee Propolis against Carbon Tetrachloride-Induced Liver Injury in Rat

    Directory of Open Access Journals (Sweden)

    Rachel Amelia

    2016-06-01

    Full Text Available Background: Oxidative stress reaction can cause liver injury. This process can be prevented by antioxidant activities which can break the destructive chain caused by free radical substances in the liver. Propolis produced by Trigona spp. bee is known to have a high level of antioxidant. The aim of this study was to examine the effect of Trigona spp. bee propolis on liver histological toxicity caused by carbon tetrachloride-induced oxidative stress. Methods:This experimental study was conducted in September 2013 at the Animal Laboratory of Departement of Pharmacology and Therapy, Faculty of Medicine Universitas Padjadjaran. Twenty-four healthy male Wistar rats as objects were adapted for one week and randomly divided into 3 groups. Group I was the control negative, group II was given carbon tetrachloride on day 14, group III was given Trigona spp. bee propolis on day 1-14. On day 14, group III was injected CCl4 intraperitoneally. The quantitative data were statistically analyzed using the one way ANOVA and Tukey test with p value < 0.05. Results: Group I showed the liver contained normal cells, without significant injury of the membrane, round and complete nucleus. The average number of liver cell was 464 ± 9.59281 cells/field; group II underwent necrosis and the average of the cells was 146 ± 7.56885 cells/field; group III showed some normal liver cells, and some necrotic area with the normal liver cells average was 263 ± 14.10860 cells/field. The p-value=0.00. Conclusions: Trigona spp. bee propolis has a hepatoprotective effect against CCl4-induced liver injury histologically.

  8. Similarity between the effects of carbon-ion irradiation and X-irradiation on the development of rat brain

    International Nuclear Information System (INIS)

    Inouye, Minoru; Hayasaka, Shizu; Murata, Yoshiharu; Takahashi, Sentaro; Kubota, Yoshihisa

    2000-01-01

    The effects of carbon-ion irradiation and X-irradiation on the development of rat brain were compared. Twenty pregnant rats were injected with bromodeoxyuridine (BrdU) at 9 pm on day 18 pregnancy and divided into five groups. Three hours after injection (day 19.0) one group was exposed to 290 MeV/u carbon-ion radiation by a single dose of 1.5 Gy. Other groups were exposed to X-radiation by 1.5, 2.0 or 2.5 Gy, or sham-treated, respectively. Fetuses were removed from one dam in each group 8 h after exposure and examined histologically. Extensive cell death was observed in the brain mantle from the irradiated groups. The cell death after 1.5 Gy carbon-ion irradiation was remarkably more extensive than that after 1.5 Gy X-irradiation, but comparable to that after 2.0 Gy or 2.5 Gy X-irradiation. The remaining rats were allowed to give birth and the offspring were sacrificed at 6 weeks of age. All of the irradiated offspring manifested microcephaly. The size of the brain mantle exposed to 1.5 Gy carbon-ion radiation was significantly smaller than that exposed to 1.5 Gy X-radiation and larger than that exposed to 2.5 Gy X-radiation. A histological examination of the cerebral cortex revealed that cortical layers II-IV were malformed. The defect by 1.5 Gy carbon-ion irradiation was more severe than that by the same dose of X-irradiation. Although the BrdU-incorporated neurons were greatly reduced in number in all irradiated groups, these cells reached the superficial area of the cortex. These findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ion irradiation compares to that of 2.0-2.5 Gy X-irradiation. (author)

  9. Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers

    International Nuclear Information System (INIS)

    Cornell, R.P.

    1982-01-01

    In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125 I-albumin microaggregates, and 125 I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125 I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans

  10. Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers.

    Science.gov (United States)

    Cornell, R P

    1982-02-01

    In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125I-albumin microaggregates, and 125I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans.

  11. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

  12. Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment.

    Science.gov (United States)

    Fukushima, Shoji; Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Sasaki, Toshiaki; Matsumoto, Michiharu

    2018-01-25

    This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m 3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

  13. Incorporation of glucose carbons into rat lung lipids after exposure to 0.6 ppm ozone

    International Nuclear Information System (INIS)

    Bassett, D.J.; Rabinowitz, J.L.

    1985-01-01

    Continuous exposure to low concentrations of ozone has previously been associated with proliferation of lung alveolar type II epithelial cells. In this study, 14 C incorporation into tissue lipids was determined in isolated rat lungs by perfusion with [U- 14 C]glucose, at a time of maximal hyperplasia brought about by 3 days continuous exposure to 0.6 ppm ozone. Ozone exposed lungs exhibited increased rates of glycolytic energy production, indicated by an 89% increase in 3 H 2 O generation on perfusion with [5-3H]glucose. Ozone exposure resulted in enhanced 14 C incorporations into glyceride-glycerol and fatty acid moieties of lung lipids of 95 and 180%, respectively, with a greater proportion of label being recovered in shorter chain fatty acids. Although increased labeling was observed in both neutral and phospholipids, the pattern of 14 C recovery suggested a relative increased glucose carbon incorporation into lung free fatty acids, phosphatidic acid, and such membrane associated lipids as phosphatidylinositol and those containing sphingosine. These results are consistent with the needs of a dividing cell population for enhanced energy production and synthesis of new lipids

  14. Long Term Influence of Carbon Nanoparticles on Health and Liver Status in Rats.

    Directory of Open Access Journals (Sweden)

    Barbara Strojny

    Full Text Available Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects.

  15. Studying the effectiveness of activated carbon R95 respirators in reducing the inhalation of combustion by-products in Hanoi, Vietnam: a demonstration study

    Directory of Open Access Journals (Sweden)

    Wertheim Heiman FL

    2012-09-01

    Full Text Available Abstract Background Urban air pollution is an increasing health problem, particularly in Asia, where the combustion of fossil fuels has increased rapidly as a result of industrialization and socio-economic development. The adverse health impacts of urban air pollution are well established, but less is known about effective intervention strategies. In this demonstration study we set out to establish methods to assess whether wearing an R95 activated carbon respirator could reduce intake of polycyclic aromatic hydrocarbons (PAH in street workers in Hanoi, Vietnam. Methods In this demonstration study we performed a cross-over study in which non-smoking participants that worked at least 4 hours per day on the street in Hanoi were randomly allocated to specific respirator wearing sequences for a duration of 2 weeks. Urines were collected after each period, i.e. twice per week, at the end of the working day to measure hydroxy PAHs (OH-PAH using gas chromatography/high resolution mass spectrometry. The primary endpoint was the urinary concentration of 1-hydroxypyrene (1-OHP. Results Forty-four participants (54.5% male, median age 40 years were enrolled with the majority being motorbike taxi drivers (38.6% or street vendors (34.1%. The baseline creatinine corrected urinary level for 1-OHP was much higher than other international comparisons: 1020 ng/g creatinine (IQR: 604–1551. Wearing a R95 mask had no significant effect on 1-OHP levels: estimated multiplicative effect 1.0 (95% CI: 0.92-1.09 or other OH-PAHs, except 1-hydroxynaphthalene (1-OHN: 0.86 (95% CI: 0.11-0.96. Conclusions High levels of urine OH-PAHs were found in Hanoi street workers. No effect was seen on urine OH-PAH levels by wearing R95 particulate respirators in an area of high urban air pollution, except for 1-OHN. A lack of effect may be de to gaseous phase PAHs that were not filtered efficiently by the respirator. The high levels of urinary OH-PAHs found, urges for effective

  16. Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

    Science.gov (United States)

    Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

    2017-02-01

    We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

  17. Study on serum metabonomics of rats exposed to low-dose ionizing radiation, carbon monoxide, benzene and noise

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    Qing-rong WANG

    2015-07-01

    Full Text Available Objective To investigate the combined effects of low-dose ionizing radiation, carbon monoxide, benzene and noise on serum metabolites and the mechanism of injury induced by these complex environmental factors in rats. Methods  Sixteen adult SD rats were randomly divided into control group and exposed group (8 each. The exposed group received the combined effect every day for 7 days. At the end of experiment, sera were collected from the abdominal aorta of rats. The metabolic fingerprint of serum was obtained by 1H nuclear magnetic resonance (1H NMR spectroscopy and determined with pattern recognition techniques of principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS. The similarities and differences in metabolic profiles between two groups were visualized by SIMCA-P software. Results The rat serum 1H NMR spectra revealed different metabolic spectra between the control group and exposed group. The OSC-PLS plots of the serum samples presented respectively marked clustering between the two groups. Compared with the control group, the contents of lipid, high density lipoprotein, glycine/glucose, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, phosphatidyl choline and unsaturated fatty acid increased, while those of lactic acid, threonine/lipid, alanine, creatine, glycerylphosphorylcholine/ trimethylamine oxide, low density lipoprotein/high density lipoprotein, low density lipoprotein, very low density lipoprotein/ low density lipoprotein, very low density lipoprotein and saturated fatty acid decreased. Conclusions Combination of low-dose ionizing radiation, carbon monoxide, benzene and noise could induce changes of serum metabolites in rats, involving in immune function, renal function and energy metabolism. The NMR-based-metabonomics method has potential of application in research on combined biological effects of the complex environmental factors. DOI: 10.11855/j.issn.0577-7402.2015.07.09

  18. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  19. The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.

    Science.gov (United States)

    Madro, Agnieszka; Słomka, Maria; Celiński, Krzysztof; Chibowski, Daniel; Czechowska, Grazyna; Kleinrok, Zdzisław; Karpińska, Agnieszka

    2002-01-01

    Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the

  20. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  1. Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method.

    Science.gov (United States)

    Shim, Ha Eun; Lee, Jae Young; Lee, Chang Heon; Mushtaq, Sajid; Song, Ha Yeon; Song, Lee; Choi, Seong-Jin; Lee, Kyuhong; Jeon, Jongho

    2018-05-25

    To assess the risk posed by a toxic chemical to human health, it is essential to quantify its uptake in a living subject. This study aims to investigate the biological distribution of inhaled polyhexamethylene guanidine (PHMG) aerosol particle, which is known to cause severe pulmonary damage. By labeling with indium-111 ( 111 In), we quantified the uptake of PHMG for up to 7 days after inhalation exposure in rats. The data demonstrate that PHMG is only slowly cleared, with approximately 74% of inhaled particles persisting in the lungs after 168 h. Approximately 5.3% of inhaled particles were also translocated to the liver after 168 h, although the level of redistribution to other tissues, including the kidneys and spleen, was minimal. These observations suggest that large uptake and slow clearance may underlie the fatal inhalation toxicity of PHMG in humans. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment.

    Science.gov (United States)

    Marković, Dejan; Jokanović, Vukoman; Petrović, Bojan; Perić, Tamara; Vukomanović, Biserka

    2014-05-01

    Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA) obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 μm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material's particles took place after 25 weeks. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects.

  3. Combined effects of inhalation of Radon daughter products and tobacco smoke

    International Nuclear Information System (INIS)

    Chameaud, J.; Perraud, R.; Chretien, J.; Masse, R.; Lafuma, J.

    1980-01-01

    Over the last 10 years, more than 500 lung cancers have been induced in rats by inhalations of radon daughter products at various concentrations and cumulated doses. These cancers were compared with human cancers. Another study examines the cocarcinogenic effect of tobacco smoke. In the first experiment, 100 rats were exposed to a 4000-WLM (working level month) cumulated dose of radon daughter products. Fifty animals were then administered tobacco smoke by inhalation in a fume box during 5 months (i.e., for a total of 352 hr). In the group inhaling radon only, 17 cancers appeared; in the radon-tobacco group, 32 cancers were observed, many of them larger and more invasive than those seen in animals exposed to radon only. Under the same conditions tobacco smoke was inhaled by rats previously exposed to lower doses of radon daughter products (two groups of 30 rats each, at 500 and 100 WLM, respectively). Again, the number of cancers observed was greater than the number of cancers expected if the rats had inhaled radon only. The carcinogenic and potentiating action of tobacco smoke was clearly demonstrated

  4. Polymer degradation and ultrafine particles - Potential inhalation hazards for astronauts

    Science.gov (United States)

    Ferin, J.; Oberdoerster, G.

    1992-01-01

    To test the hypothesis that exposure to ultrafine particles results in an increased interstiatilization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO2 particles access the pulmonary interstitium to a larger extent than fine particles and that they elicit an inflammatory response as indicated by PMN increase in lavaged cells. The release of ultrafine particles into the air of an enclosed environment from a thermodegradation event or from other sources is a potential hazard for astronauts. Knowing the mechanisms of action is a prerequisite for technical or medical countermeasures.

  5. Prophylactic effect of four prescriptions of traditional Chinese medicine on alpha-naphthylisothiocyanate and carbon tetrachloride induced toxicity in rats.

    Science.gov (United States)

    Lin, K J; Chen, J C; Tsauer, W; Lin, C C; Lin, J G; Tsai, C C

    2001-12-01

    To study the prophylactic effects of four Chinese traditional prescriptions against experimental liver injury. Liver toxins, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4) were used to induce acute liver injury. Simo Yin(SMY), Guizhi Fuling Wan (GFW), Xieqing Wan (XQW), and Sini San (SNS) were fed (500 mg/kg, in saline, po) to the rats before toxin administration. All the animals were killed 48 h after toxin insulted. Serum index of liver function and hepatic lipid peroxidation (LPO) were estimated. Histopathological observation was conducted simultaneously. The rats treated with ANIT exhibited elevations of serum total bilirubin (TBI), alkaline phosphatase (ALP), glutamate-oxalate- transaminase (GOT), glutamate-pyruvate-transaminase (GPT), as well as cholestasis and parenchyma necrosis. In rats, challenged with ANIT, receiving the pre-treatment of prescriptions of SMY, XQW, and SNS, the biochemical and morphological parameters of liver injury were significantly reduced. The increased LPO level in liver tissue, associated with the provoked serum GOT and GPT levels were the salient features observed in CCl4-insulting rats. Pre-treatment of four prescriptions showed a remarkable protective effect, and also was effective in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative level. These recipes ameliorate liver damage induced by both ANIT and CCl4 despite the differences in their mechanisms of injury. Therefore they may be able to exert hepatoprotective effects through more than one mechanism of action because they contained a mixture of anti-hepatotoxic ingredients with mutual reinforcement and assistance.

  6. Protection of the Extracts of Lentinus edodes Mycelia against Carbon-Tetrachloride-Induced Hepatic Injury in Rats

    Directory of Open Access Journals (Sweden)

    Mei-Fen Chen

    2012-01-01

    Full Text Available Lentinus edodes is the medicinal macrofungus showing potential for therapeutic applications in infectious disorders including hepatitis. In an attempt to develop the agent for handling hepatic injury, we used the extracts of Lentinus edodes mycelia (LEM to screen the effect on hepatic injury in rats induced by carbon tetrachloride (CCl4. Intraperitoneal administration of CCl4 not only increased plasma glutamic oxaloacetic transaminase (GOT and glutamic pyruvic transaminase (GPT but also decreased hepatic superoxide dismutase (SOD and glutathione peroxidase (GPx levels in rats. Similar to the positive control silymarin, oral administration (three times daily of this product (LEM for 8 weeks significantly reduced plasma GOT and GPT. Also, the activities of antioxidant enzymes of SOD and GPx were elevated by LEM. in liver from CCl4-treated rats, indicating that mycelium can increase antioxidant-like activity. Moreover, the hepatic mRNA and protein levels of SOD and GPx were both markedly raised by LEM. The obtained results suggest that oral administration of the extracts of Lentinus edodes mycelia (LEM has the protective effect against CCl4-induced hepatic injury in rats, mainly due to an increase in antioxidant-like action.

  7. Utilization of [1-14C]carbon of glycine of high glycine diet fed young and old rats

    International Nuclear Information System (INIS)

    Petzke, K.J.; Albrecht, V.; Medovar, B.Ya.; Pisarczuk, K.L.; Grigorov, Yu.G.

    1987-01-01

    The incorporation of radioactivity from [1- 14 C]glycine was studied in various organ (serum, liver, muscle) fractions (acid soluble, proteins, lipids, liver glycogen) and carbon dioxide in rats fed with isonitrogenous isocaloric purfied diets. The diets contained 30% casein (control), gelatin (exchange of half of the 30% casein) or glycine (corresponding level of glycine in relation to the gelatin diet). The incorporation of radioactivity into proteins was reduced by feeding high glycine diets in young (20-weeks-old) and old (18-month-old) rats in relation to the control diet. The modifications of the results for old animals may be partially explained on the base of a reduced protein turnover rate and adaptation to a high gelatin (glycine) diet. (author)

  8. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

    1978-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

  9. Toxicity of inhaled Ca-DTPA in the beagle dog

    International Nuclear Information System (INIS)

    Smith, V.H.; Ragan, H.A.; Lund, J.E.; Hackett, P.L.

    1975-01-01

    There are several advantages to the administration of Ca- DTPA by inhalation rather than intravenous drip for the decorporation of certain radionuclides. Among these are the possibility of treating very promptly following an accidental incorporation to achieve maximum treatment effectiveness and convenince for medical management, even to the extent that treatment can be self-administered. The present investigational New Drug permit allows treatment of humans only by the intravenous route and animal studies are required to justify the new route. Earlier work in rats and hamsters showed five successive daily inhalations of Ca-DTPA aerosols (dose 1 to 4 times human i.v. dose) produced a transitory emphysema in 17/40 rats serially sacrificed up to 3 weeks following the last exposure and in 10/20 hamsters up to 1 week after exposure. No emphysema was seen in rats sacrificed after 3 weeks and in hamsters after 1 week following the exposures. Results of tests in dogs administered DTPA by inhalation showed hyperplasia of the gastric submucosal lymphoid follicles observed 1 week following the last exposure may be treatment-related, but other observed changes were considered unrelated. (U.S.)

  10. Model for deposition and long-term disposition of 134Cs-labeled fused aluminosilicate particles inhaled by guinea pigs

    International Nuclear Information System (INIS)

    Snipes, M.B.; McClellan, R.O.

    1986-01-01

    When considering which laboratory animal species to use in inhalation studies, it is important to evaluate the similarities and differences in deposition and fate of the inhaled materials in various laboratory animals compared with humans. Beagle dogs have deposition and clearance patterns of inhaled particles similar to humans. However, some studies require smaller laboratory animals to be cost effective or to allow an adequate number of animals to address the scientific questions. This study evaluated the deposition and clearance of a relatively insoluble aerosol inhaled by guinea pigs. The test aerosol was monodisperse 134 Cs-labeled fused aluminosilicate particles inhaled during 75 minute inhalation exposure. The guinea pigs had deposition similar to rats but respiratory tract retention and clearance patterns were similar to dogs and humans. 5 references, 2 figures, 1 table

  11. Species difference in metabolism of inhaled butadiene

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Dahl, A.R.; Bechtold, W.E.; Henderson, R.F.; Burka, L.T.

    1991-01-01

    Chronic exposure of B6C3F 1 mice and Sprague-Dawley rats to butadiene (BD) produced a very high incidence of cancer in mice while the incidence in rats was much lower with different tissues affected. Studies at this institute indicate that for equivalent exposures, the blood BD epoxide concentrations in mice are 5-fold higher than in rats and > 10-fold higher than in Cynomolgus monkeys. In this study, the profiles of urinary metabolites of butadiene were determined in Cynomolgus monkeys, F344/N rats, Sprague Dawley rats, B6C3F 1 mice and Syrian hamsters, species containing widely divergent hepatic epoxide hydrolase (EH) activities. Animals were exposed for 2 hr to 8,000 ppm [ 14 C]BD and 24-hr urine samples were analyzed for metabolites. Two major urinary metabolites were identified, N-acetyl-S-(-1(or 2)-3-butene-2(or 1)-ol)cysteine (1) and N-acetyl-S-(-4-butane-1,2-diol)cysteine (2). Monkeys exposed by inhalation produced primarily metabolite 2, while rodent species produced 1-4 times as much of 1 compared to 2. The ratio of 2/1 formation was related to the hepatic epoxide hydrolase activity in different species. The high 2/1 ratio in monkeys was consistent with the lower blood epoxide levels in this species. If BD metabolism by humans is similar to that in the monkey, exposure of humans to BD may result in lower tissue concentrations of reactive metabolites than an equivalent exposure of rodents. This has important implications for assessing the risk to humans of BD exposure based on rodent studies

  12. Inhaled Corticosteroids (ICSs) and Pregnancy

    Science.gov (United States)

    ... of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. ... of medicine that would be in the breast milk following inhalation is likely too small to cause ...

  13. Particle exposure and inhaled dose during commuting in Singapore

    Science.gov (United States)

    Tan, Sok Huang; Roth, Matthias; Velasco, Erik

    2017-12-01

    Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

  14. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

  15. Respirable versus inhalable dust sampling

    International Nuclear Information System (INIS)

    Hondros, J.

    1987-01-01

    The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

  16. Carbon monoxide-Releasing Molecule-2 (CORM-2 attenuates acute hepatic ischemia reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Zhang Weihui

    2010-05-01

    Full Text Available Abstract Background Hepatic ischemia-reperfusion injury (I/Ri is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO by application of so-called CO-releasing molecules (CORMs. Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model. Methods Forty male Wistar rats were randomly assigned into four groups (n = 10. Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg, which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration. Results A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in

  17. Carbon monoxide contributes to the constipating effects of granisetron in rat colon.

    Science.gov (United States)

    Nacci, Carmela; Fanelli, Margherita; Potenza, Maria Assunta; Leo, Valentina; Montagnani, Monica; De Salvia, Maria Antonietta

    2016-11-14

    To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron. For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) or CO-releasing molecule-3 (CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment with or without atropine (3 μmol/L, a muscarinic receptor antagonist) or N G -nitro-L-Arginine (L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor). Administration of granisetron (50, 75 μg/kg) in vivo significantly increased the time to first defecation ( P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of ZnPPIX or hemin alone had no effect on this gastrointestinal motility parameter, ZnPPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro , granisetron alone (3 μmol/L) did not significantly modify the colon's contractile response to either EFS or ACh. Incubation with ZnPPIX alone (10 μmol/L) significantly reduced the colon's contractile response to EFS ( P = 0.016) but had no effect on contractile response to ACh. Co-administration of ZnPPIX and atropine (3 μmol/L) abolished the ZnPPIX-mediated decrease

  18. Sodium Carbonate is Saltier Than Sodium Chloride to Sodium-Depleted Rats.

    Science.gov (United States)

    St John, Steven J; McBrayer, Anya M; Krauskopf, Erin E

    2017-10-01

    In a series of behavioral experiments in the 1960s, G.R. Morrison identified several unique features of the taste of Na2CO3 to rats; namely, it is 1) considerably more intense than NaCl at isomolar concentrations, 2) avoided at 10 times lower concentrations than NaCl to thirsty rats, 3) preferred at 10 times lower concentrations than NaCl in sodium-depleted rats. He also demonstrated its qualitatively similarity to NaCl. In Experiment 1, we confirmed and extended many of Morrison's observations. Rats were injected with furosemide on 3 occasions to stimulate a sodium appetite. After each depletion, rats were given a brief-access taste test in a lickometer presenting, in random order, water and 7 concentrations of salt. One test used NaCl (0.028-0.89 M, quarter log steps), another used Na2CO3, and the third used Na2CO3, but at a tenfold lower concentration range (0.0028-0.089 M). Rats licked NaCl in an inverted-U shaped concentration-response function peaking at 0.158-0.281 M. As Morrison's results predicted, rats licked Na2CO3 in nearly identical fashion, but at a tenfold lower concentration range (peak at 0.0158-0.028 M). In a second experiment, furosemide-treated rats were repeatedly tested with the lower Na2CO3 range but mixed in the epithelial sodium channel blocker amiloride at various concentrations (3-300 μM, half log steps). Amiloride reduced licking for Na2CO3 and shifted the peak response rightward up to about half a log unit. Thus, this "super-saltiness" of Na2CO3 to rats is at least partly amiloride-dependent. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. The concentration of "1"3"7Cs and organic carbon on sediment at Rat island in Indian ocean

    International Nuclear Information System (INIS)

    Muslim; Reza Agung Arjana; Wahyu Retno Prihatiningsih

    2016-01-01

    Rat Island is one of the islands in Indonesia, located in the Indian Ocean, about 10 kilometers west of Bengkulu, which has a beautiful scenery both on its land and on the seabed, making it a favorite tourist in Bengkulu. The purpose of this study was to determine the condition of "1"3"7Cs in sediments and its relation to the total carbon and sediment texture. Sediment sampling carried out on 17 September 2014 at six stations where three stations are still relatively close to The Rat island with water depth of ≤ 1 m and 3 others are far from Rat Island waters with a depth of 14-18 meters. Sediment texture and TOC content at waters depth of ≤ 1 m is sand and its TOC contents were <5.5%. On other hand at water depth of 14-18 meters sediment texture are silt sand mixture and the TOC content were ≥6%. The concentration of "1"3"7Cs in sediment were influenced by texture characteristic and TOC content. (author)

  20. Effect of Apitherapy Formulations against Carbon Tetrachloride-Induced Toxicity in Wistar Rats after Three Weeks of Treatment

    Directory of Open Access Journals (Sweden)

    Calin Vasile Andritoiu

    2014-08-01

    Full Text Available The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution. Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.

  1. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

  2. The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment

    Directory of Open Access Journals (Sweden)

    Marković Dejan

    2014-01-01

    Full Text Available Background/Aim. Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. Methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 μm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. Results. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material’s particles took place after 25 weeks. Conclusion. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects. [Projekat Ministarstva nauke Republike Srbije, br. 172026

  3. Protective effect of a coffee preparation (Nescafe pure) against carbon tetrachloride-induced liver fibrosis in rats.

    Science.gov (United States)

    Shi, Hongyang; Dong, Lei; Zhang, Yong; Bai, Yanhua; Zhao, Juhui; Zhang, Li

    2010-06-01

    We examined the effects of a coffee preparation on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms. Rats were divided randomly into four groups: control, CCl(4), and two coffee preparation groups. Except for the control group, liver fibrosis was induced in male Sprague-Dawley (SD) rats by subcutaneous injection with 40% CCl(4) twice a week for 8 weeks. At the same time, a coffee preparation (300 mg/kg and 150 mg/kg) was administered to the two coffee preparation groups intragastrically once daily. Upon pathological examination, a coffee preparation treatment significantly reduced liver damage and symptoms of liver fibrosis. The mRNA expression of collagen I, collagen III, bcl-2, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) were markedly increased by CCl(4) treatment but suppressed by a coffee preparation treatment. Whereas compared with the CCl(4) group, the mRNA expression of Bax was increased in the coffee preparation group. The protein expression of Bax and bcl-2 were confirmed by western blot. Intragastric administration of a coffee preparation reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl(4). Our data indicate that a coffee preparation can efficiently inhibit CCl(4)-induced liver fibrosis in rats. The coffee preparation may therefore be a potential functional food for preventing liver fibrosis. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-12-01

    Full Text Available Abstract Background Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs following inhalation of UfCPs (24 h, 172 μg·m-3, to assess whether compromised animals (SHR exhibit a different response pattern compared to the previously studied healthy rats (WKY. Methods Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1, blood coagulation (tissue factor, plasminogen activator inhibitor-1, and endothelial function (endothelin-1, and endothelin receptors A and B were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF. Results Increased BP and heart rate (HR by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary and blood (systemic were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p Conclusion Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction

  5. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides.

    Directory of Open Access Journals (Sweden)

    Dongmei Wang

    Full Text Available Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD. Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT. Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612 phosphorylation and decreased S6K phosphorylation (240/244 but only MCT10 increased Akt phosphorylation (473. MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1 were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels.

  6. Assessment of the hepatoprotective activity of the seeds of Hunteria umbellata (Hallier F.) on carbon tetrachloride (CCl4) induced liver damage in Wistar albino rats

    Science.gov (United States)

    Ogunlana, Olubanke Olujoke; Ogunlana, Oluseyi Ebenezer; Adelani, Isaacson Bababode; Adebayo, Angie Osariem Igbinoba; David, Opetoritse Laju; Adeleye, Oluwaseye Joseph; Udeogu, Stephanie Adaora; Adeyemi, Alaba Oladipupo; Akinyele, Julie Oluranti

    2018-04-01

    This study was designed to evaluate the hepatoprotective activity of the seeds of Hunteria umbellata (HU) on carbon tetrachloride (CCl4) induced rats. Rats of groups 1 (normal control), 3 and 5 were not treated with CCl4 while rats of groups 2 (negative control), 4 and 6 rats were treated with single dose of CCl4 (2 ml/kg) by intraperitoneal administration. Normal control group 1 rats were given distilled water, groups 3 and 4 rats were given 50 mg/kg of silymarin while groups 5 and 6 rats were given 500 mg/kg of HU. Treatment was administered orally for 28 days and sacrificed on the 29th day after an overnight fast. The weights of the rats were taken before and after the treatment. Blood samples were collected in heparinized tubes and biochemical analysis of liver functions and lipid profile tests were carried out on plasma. There was a significant change (pgroup treated with HU compared to the CCl4 untreated group 2 animals. The results obtained showed that the ethanolic extract of HU has hepatoprotective property.

  7. Toxicity studies of inhaled beta-emitting radionuclides - Status report

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F F; Boeker, B B; Gillett, N A; Griffith, W C; Lundgren, D L; McClellan, R O; Muggenburg, B A; Snipes, M B

    1988-12-01

    The effects of beta-emitting radionuclides inhaled in either a relatively soluble form ({sup 90}SrCl{sub 2}, {sup 144}CeCl{sub 3}, {sup 91}yl{sub 3}, or {sup 137}CsCl) or in a relatively insoluble form ({sup 90}Y, {sup 91}Y, {sup 144}Ce or {sup 90}Sr in fused aluminosilicate particles [FAP]) have been studied in laboratory animals. The results showed that the total beta dose and the dose-rate pattern can modify both the neoplastic and non-neoplastic effects of inhaled beta-emitting radionuclides. In addition, the solubility and chemical characteristics of the radionuclides influence which organs are affected. Effects are seen primarily in organs where the radionuclide is ultimately accumulated, e.g., lung, bone, liver, or tracheobronchial lymph nodes. In addition, effects may be seen in organs where there is little accumulation, but where the radiation dose may still be high, e.g., nasal epithelium and heart. Studies of inhaled {sup 144}Ce-FAP in four different species showed that, compared to mice and dogs, lung tumor risk factors are very low for Syrian hamsters and high for rats. Studies of mice, Syrian hamsters, rats, and dogs repeatedly exposed to aerosols of {sup 144}Ce-FAP showed that lung tumor incidence correlates better with cumulative dose to the lung than with dose rate. Most of the studies in this program are nearing completion and full analyses are in progress. (author)

  8. A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats.

    Science.gov (United States)

    Eluwa, M A; Inyangmme, I I; Akpantah, A O; Ekanem, T B; Ekong, M B; Asuquo, O R; Nwakanma, A A

    2013-09-01

    Carbonated drinks are widely consumed because of their taste and their ability to refresh and quench thirst. These carbonated drinks also exist in the form of diet drinks, for example Diet Coke®, Pepsi®, extra. A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of female albino Wistar rats was investigated. Fifteen adult female Wistar rats weighing between 180-200 g were divided into 3 groups; designated as groups A, B and C, and each group consisted of five rats. Group A was the Control group and received distilled water, while groups B and C were the experimental groups. Group B was administered 50 ml of regular soda (RS), and group C was administered 50 ml of diet soda (DS) each per day for 21 days, and the rats were sacrificed on Day 22, and their cerebellums excised and preserved. Histological result of the sections of the cerebellum showed shrunken and degenerated Purkinje cells with hypertrophied dendrites, especially in the DS group, which was less in the RS group compared to the control group. These results suggest that diet soda has adverse effect on the cerebellum of adult female albino Wistar rats.

  9. Carbonated soft drinks alter hepatic cytochrome P450 isoform expression in Wistar rats.

    Science.gov (United States)

    Alkhedaide, Adel; Soliman, Mohamed Mohamed; Ibrahim, Zein Shaban

    2016-11-01

    The aim of the current study was to examine the effects of chronic consumption of soft drinks (SDs) on hepatic oxidative stress and cytochrome P450 enzymes (CYPs) expression in the livers of Wistar rats. For 3 consecutive months, the rats had free access to three different soft drinks, Coca-Cola, Pepsi-Cola and 7-UP. The rats were subsequently compared with control group rats that had consumed water. Blood and hepatic tissue samples were assayed for the changes in antioxidants, liver function biomarkers and hepatic gene expression for different isoforms of hepatic CYP. The results indicated that SD consumption (SDC) decreased serum antioxidant levels and increased malondialdehyde secretion, and increased liver biomarkers (glutamate pyruvate transaminase and glutamate oxaloacetate). SD induced alterations in mRNA expression of hepatic antioxidants and cytochrome isoforms. The expression of peroxidase, catalase, CYP1A2, CYP3A2 and CYP2C11 in the liver were upregulated following SDC. By contrast, CYP2B1 was downregulated after 3 months of SDC in liver tissue samples. Thus, the present findings indicate that SDs induced oxidative stress in the liver of Wistar rats and for the first time, to the best of our knowledge, indicate that SDC disrupts hepatic CYP enzymes that may affect drug metabolism. Therefore, drug-dosing programs should be carefully designed to take these novel findings into consideration for the treatment of diseases.

  10. Vasomotor function in rat arteries after ex vivo and intragastric exposure to food-grade titanium dioxide and vegetable carbon particles

    DEFF Research Database (Denmark)

    Jensen, Ditte Marie; Christophersen, Daniel Vest; Sheykhzade, Majid

    2018-01-01

    -grade particle exposure on vasomotor function and systemic oxidative stress in an ex vivo study and intragastrically exposed rats.Methods: In an ex vivo study, aorta rings from naive Sprague-Dawley rats were exposed for 30 min to food-grade TiO2 (E171), benchmark TiO2 (Aeroxide P25), food-grade vegetable carbon...... (E153) or benchmark carbon black (Printex 90). Subsequently, the vasomotor function was assessed in wire myographs. In an in vivo study, lean Zucker rats were exposed intragastrically once a week for 10 weeks to vehicle, E171 or E153. Doses were comparable to human daily intake. Vasomotor function...... no differences between groups.Conclusion: Gastrointestinal tract exposure to E171 and E153 was associated with modest albeit statistically significant alterations in the vasocontraction and vasorelaxation responses. Direct particle exposure to aorta rings elicited a similar type of response. The vasomotor...

  11. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1987-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

  12. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1986-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

  13. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1982-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  15. Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Carratu, M.R. (Inst. of Pharmacology, Bari Univ. (Italy)); Renna, G. (Inst. of Pharmacology, Bari Univ. (Italy)); Giustino, A. (Inst. of Pharmacology, Bari Univ. (Italy)); De Salvia, M.A. (Inst. of Pharmacology, Bari Univ. (Italy)); Cuomo, V. (Inst. of Pharmacology, Bari Univ. (Italy))

    1993-06-01

    The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h[sub [infinity

  16. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  17. Electrostatic Properties of Particles for Inhalation

    OpenAIRE

    Rowland, Martin

    2015-01-01

    Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

  18. Inhalation Injury: State of the Science 2016.

    Science.gov (United States)

    Foster, Kevin N; Holmes, James H

    This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

  19. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  20. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

  2. Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP Synthesized from Porous Foraminifera Carbonate Macrospheres

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    2013-12-01

    Full Text Available Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.

  3. Effect of carbon tetrachloride and Liv-52 on the clearance rate of 131I-Rose bengal in rat liver

    International Nuclear Information System (INIS)

    Dhawan, D.; Goel, A.; Karkara, K.

    1991-01-01

    131 I-Rose bengal clearance test has been immensely used for the clinical assessment of functional hepatic abnormalities. It has been observed that external collimated scintillation probe employing 131 I-Rose bengal is a rapid and less erroneous way of assessing polygonal cell function in liver. The present study demonstrates the protection of liver by Liv-52 from the deleterious effects of carbon tetrachloride (CCl 4 ) by determining the biological half-life of 131 I-Rose bengal in male albino rats. An increase in the biological half-life of the radio-iodinated dye was observed following CCl 4 intoxication which was reversed by Liv-52 treatment. (author). 15 refs., 2 tabs

  4. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes

    DEFF Research Database (Denmark)

    Folkmann, Janne K; Risom, Lotte; Jacobsen, Nicklas R

    2009-01-01

    BACKGROUND: C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might...... be the initiating event in the development of cancer. OBJECTIVE: In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. METHODS: We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa...... of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. CONCLUSIONS: Oral exposure to low doses of C60...

  5. Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes

    Directory of Open Access Journals (Sweden)

    Paulo Francisco Guerreiro Cardoso

    2011-10-01

    Full Text Available OBJETIVO: Apresentar um modelo experimental de administração de prostaglandina I2 (PGI2 por via inalatória vs. parenteral e avaliar o desempenho funcional dos pulmões em um sistema de perfusão pulmonar ex vivo. MÉTODOS: Quarenta ratos Wistar foram anestesiados, ventilados, submetidos a laparotomia com ressecção do esterno e anticoagulados. O tronco da artéria pulmonar foi canulado. Todos os animais foram submetidos a ventilação mecânica. Os animais foram randomizados em quatro grupos (10 ratos/grupo: salina nebulizada (SN; salina parenteral (SP; PGI2 nebulizada (PGI2N; e PGI2 parenteral (PGI2P. A dose de PGI2 nos grupos PGI2N e PGI2P foi de 20 e 10 µg/kg, respectivamente. Os blocos cardiopulmonares foram submetidos in situ a perfusão anterógrada com solução de baixo potássio e dextrana a 4ºC via artéria pulmonar, extraídos em bloco e armazenados a 4ºC por 6 h. Os blocos foram ventilados e perfundidos em um sistema ex vivo por 50 min, sendo obtidas medidas de mecânica ventilatória, hemodinâmica e trocas gasosas. RESULTADOS: Houve redução da pressão arterial pulmonar média após a nebulização em todos os grupos (p OBJECTIVE:To present a model of prostaglandin I2 (PGI2 administration (inhaled vs. parenteral and to assess the functional performance of the lungs in an ex vivo lung perfusion system. METHODS: Forty Wistar rats were anesthetized and placed on mechanical ventilation followed by median sterno-laparotomy and anticoagulation. The main pulmonary artery was cannulated. All animals were maintained on mechanical ventilation and were randomized into four groups (10 rats/group: inhaled saline (IS; parenteral saline (PS; inhaled PGI2 (IPGI2; and parenteral PGI2 (PPGI2. The dose of PGI2 used in the IPGI2 and PPGI2 groups was 20 and 10 µg/kg, respectively. The heart-lung blocks were submitted to antegrade perfusion with a low potassium and dextran solution via the pulmonary artery, followed by en bloc extraction and

  6. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    International Nuclear Information System (INIS)

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-01-01

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  7. Gene expression and enzyme activities of carbonic anhydrase and glutaminase in rat kidneys induced by chronic systemic hypoxia

    Directory of Open Access Journals (Sweden)

    Andi N.K. Syarifin

    2015-11-01

    Full Text Available Background: Hypoxia can cause acidosis. Kidney plays an essential role in maintaining acid-base balance, which involves the activities of carbonic anhydrase (CA and glutaminase (GLS. This study is aimed to determine the expression and activities of the CA9 and GLS1 enzymes in relation to hypoxia inducible factor-1α (HIF-1α, a transcription factor protein which is a marker of hypoxia.Methods: This study was an in vivo experimental study with coupled paralel design. used 25 male Sprague-Dawley rats weighing 150-200 g. Rats were divided into 5 groups: the control group (normoxic condition and 4 treatment groups. The latter were kept in a hypoxic chamber (10% O2: 90% N2 for 1, 3, 5 and 7 days. All rats were euthanized after treatment, kidneys excised, tissues homogenized and investigated for gene expression of CA9, GLS1 and HIF-1α. On protein level, total enzymatic activities of CA and GLS and protein of HIF-1α were also investigated. Data were analyzed statistically using ANOVA for significance, and as its alternative, used Mann-Whitney and Kruskal-Wallis test.Results: Results showed that HIF-1α mRNA increased during hypoxia, but not HIF-1α protein. It seemed that acidosis occurs in kidney tissue, indicated by increased CA9 and GLS1 mRNA expression and specific activity of total CA and GLS1. Expression of CA9 and GLS1 mRNA both showed strong positive correlation with HIF-1α mRNA, but not with HIF-1α protein.Conclusion: It is suggested that during chronic systemic hypoxia, gene expression of CA9 and GLS1 and their enzyme activities were increased as a response to acidosis and related with the expression of HIF-1α mRNA.

  8. Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

    Science.gov (United States)

    Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

    2018-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

  9. Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

    Science.gov (United States)

    Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

    2013-01-01

    In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  10. Nigella sativa improves the carbon tetrachloride-induced lung damage in rats through repression of erk/akt pathway

    Directory of Open Access Journals (Sweden)

    Abdullah Aslan

    2015-08-01

    Full Text Available The objective of this study was to examine whether Nigella sativa plays a protective role against the damage in the lung by administering carbon tetra-chloride (CCl4 to rats. Male Wistar albino (n=28, 8 weeks old rats were divided into 4 groups: a negative control: Normal water consuming group to which no CCl4 and N. sativa was administered; b Positive control: Normal water consuming group to which no CCl4 was administered but N. sativa was administered; c CCl4 Group: Normal water consuming and group to which CCl4 was administered (1.5 mL/kg, ip; d N. sativa plus CCl4 group: CCl4 and N. sativa administered group (1.5 mL/kg, ip. Caspase-3, caspase -9, erk, akt protein syntheses were examined via Western blotting. Malondialdehyde determination in lung tissue was made using spectrophotometer. As a results, malondialdehyde amount was decreased in the CCl4 plus N. sativa group in comparison to CCl4 group whereas caspase-3, caspase-9 was increased and erk, akt had decreased. These results show that N. sativa protects the lung against oxidative damage.

  11. A proteomic method for analysis of CYP450s protein expression changes in carbon tetrachloride induced male rat liver microsomes

    International Nuclear Information System (INIS)

    Jia Nuan; Liu Xin; Wen Jun; Qian Linyi; Qian Xiaohong; Wu Yutian; Fan Guorong

    2007-01-01

    Carbon tetrachloride (CCl 4 ) is a well-known model compound for producing chemical hepatic injury. Cytochrome P450 is an important monooxygenase in biology. We investigated the CYP450 protein expression in the in vivo hepatotoxicity of rats induced by CCl 4 . In this experiment, CCl 4 were administered to male rats, and their livers at 24 h post-dosing were applied to the proteomic analysis. Blood biochemistry and histopathology were examined to identify specific changes. At the same time, a novel acetylation stable isotopic labeling method coupled with LTQ-FTICR mass spectrometry was applied to disclose the changes of cytochrome P450 expression amounts. The quantitative proteomics method demonstrated its correlation coefficient was 0.9998 in a 100-fold dynamic range and the average ratio of the labeled peptides was 1.04, which was very close to the theoretical ratio of 1.00 and the standard deviation (S.D.) of 0.21. With this approach, 17 cytochrome P450 proteins were identified and quantified with high confidence. Among them, the expression amount of 2C11, 3A2, and 2 E1 were down-regulated, while that of 2C6, 2B2, and 2B1 were up-regulated

  12. RNA–Stable-Isotope Probing Shows Utilization of Carbon from Inulin by Specific Bacterial Populations in the Rat Large Bowel

    Science.gov (United States)

    Lawley, Blair; Munro, Karen; Sims, Ian M.; Lee, Julian; Butts, Christine A.; Roy, Nicole

    2014-01-01

    Knowledge of the trophisms that underpin bowel microbiota composition is required in order to understand its complex phylogeny and function. Stable-isotope (13C)-labeled inulin was added to the diet of rats on a single occasion in order to detect utilization of inulin-derived substrates by particular members of the cecal microbiota. Cecal digesta from Fibruline-inulin-fed rats was collected prior to (0 h) and at 6, 12, 18 and 24 h following provision of the [13C]inulin diet. RNA was extracted from these cecal specimens and fractionated in isopycnic buoyant density gradients in order to detect 13C-labeled nucleic acid originating in bacterial cells that had metabolized the labeled dietary constituent. RNA extracted from specimens collected after provision of the labeled diet was more dense than 0-h RNA. Sequencing of 16S rRNA genes amplified from cDNA obtained from these fractions showed that Bacteroides uniformis, Blautia glucerasea, Clostridium indolis, and Bifidobacterium animalis were the main users of the 13C-labeled substrate. Culture-based studies of strains of these bacterial species enabled trophisms associated with inulin and its hydrolysis products to be identified. B. uniformis utilized Fibruline-inulin for growth, whereas the other species used fructo-oligosaccharide and monosaccharides. Thus, RNA–stable-isotope probing (RNA-SIP) provided new information about the use of carbon from inulin in microbiota metabolism. PMID:24487527

  13. Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system

    International Nuclear Information System (INIS)

    Yoshida, Yukari; Katoh, Hiroyuki; Nakano, Takashi; Suzuki, Yoshiyuki; Al-Jahdari, Wael S.; Shirai, Katsuyuki; Hamada, Nobuyuki; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2012-01-01

    The purpose of this study was to clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-μm-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer=108 keV/μm). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena. (author)

  14. Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

    Full Text Available Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1, interferon gamma (IFN-γ, programmed cell death-receptor (Fas and Tumor necrosis factor-alpha (TNF-α mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA, cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

  15. Effect Of Inhalation Exposure To Kerosene And Petrol-Fumes On ...

    African Journals Online (AJOL)

    Changes in total body weight, some anaemia-diagnostic indices (haematocrit or packed cell volume (PCV), haemoglob