Boron absorption imaging in rat lung colon adenocarcinoma metastases

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Altieri, S [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Bortolussi, S [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Bruschi, P [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Fossati, F [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Vittor, K [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Nano, R [Dipartimento di Biologia Animale Universita degli Studi di Pavia (Italy); Facoetti, A [Dipartimento di Biologia Animale Universita degli Studi di Pavia (Italy); Chiari, P [Dipartimento di Fisica Nucleare e Teorica Universita degli Studi di Pavia (Italy); Bakeine, J [Dipartimento di Scienze Biomediche e Biotecnologie Universita degli Studi di Brescia (Italy); Clerici, A [Dipartimento di Chirurgia Universita degli Studi di Pavia (Italy); Ferrari, C [Dipartimento di Chirurgia Universita degli Studi di Pavia (Italy); Salvucci, O [Dipartimento di Scienze Biomediche e Biotecnologie Universita degli Studi di Brescia (Italy)

2006-05-15

Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher {sup 10}B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of {sup 10}B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway

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Yuqing Wu

2013-01-01

and 20 μg/kg significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF-α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

Effect of irradiation on glycosaminoglycans connect in rat tissue

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Drozdz, M; Kucharz, E; Glowacki, A; Zylka, J

1981-01-01

Glycosaminoglycan (GAGs) fractions were determined in tissues (skin, liver, lungs, aortic wall) and blood serum of rats irradiated with a single dose of 500 R. An increase of total GAGs as well as changes in the fractions were found in the tissues and urine of exposed rats.

Peribronchial innervation of the rat lung.

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Artico, Marco; Bosco, Sandro; Bronzetti, Elena; Felici, Laura M; Pelusi, Giuseppe; Lo Vasco, Vincenza Rita; Vitale, Marco

2004-10-01

Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

International Nuclear Information System (INIS)

Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Influence of industrial dust of uranium ore on rats' lung tissue

International Nuclear Information System (INIS)

Jumasheva, R.T.

2010-01-01

Under the conditions of radiotoxic influence of uranium ore dust (UOD), the respiratory organs are the main system specifically responsible for adaptation to this factor. At the same time, there are not sufficient studies regarding the morphological aspects of structural lung distortions due to inhalational influence by UOD. To identify the nature of morphological changes in the animals' lung tissue at the cellular and subcellular levels under the influence of industrial dust of uranium ore in a dose of 50 MPC. Experimental studies were conducted on 80 white rats (tom) with a body mass of 120-180 g. The experimental animals were subjected to chronic inhalation of UOD in a dose of 50 MPC (107.75 mg/m 3 ). The animals that were kept in similar chambers but that were not exposed to UOD served as control animals. Material from the animals for research was withdrawn in 3, 7, 30 and 60 days after the beginning of the experiment. The animals were withdrawn from the experiment by decapitation after a brief ether anesthesia. The lung tissue was subjected to conventional histological processing. Sections were stained with haematoxylin and eosin according to van Gieson's method. For electronic microscopic examination the lung tissue slices were fixed and embedded by conventional methods. Obtained blocks were used to prepare ultrathin sections. An impact of UOD in a dose of 50 MPC was accompanied by the development of acute focal serous inflammation in the wall of the small bronchi and lung parenchyma in the early stages of the experiment (3-7 days), pneumonic foci of fibrosis, and the development of marked sclerotic changes in the peribronchial lymphoid tissue by the 30-th day. By the 60-th day, an increase of sclerotic changes in the bronchial wall accompanied by inhibition of the reaction on the part of interstitial macrophages and bronchus associated lymphoid tissue were reported. These indicate the intense course of the compensatory processes. Conducted electron

Protein synthesis in the growing rat lung

International Nuclear Information System (INIS)

Kelley, J.; Chrin, L.

1986-01-01

Developmental control of protein synthesis in the postnatal growth of the lung has not been systematically studied. In male Fischer 344 rats, lung growth continues linearly as a function of body weight (from 75 to 450 g body weight). To study total protein synthesis in lungs of growing rats, we used the technique of constant intravenous infusion of tritiated leucine, an essential amino acid. Lungs of sacrificed animals were used to determine the leucine incorporation rate into newly synthesized protein. The specific radioactivity of the leucine associated with tRNA extracted from the same lungs served as an absolute index of the precursor leucine pool used for lung protein synthesis. On the basis of these measurements, we were able to calculate the fractional synthesis rate (the proportion of total protein destroyed and replaced each day) of pulmonary proteins for each rat. Under the conditions of isotope infusion, leucyl-tRNA very rapidly equilibrates with free leucine of the plasma and of the extracellular space of the lung. Infusions lasting 30 minutes or less yielded linear rates of protein synthesis without evidence of contamination of lung proteins by newly labeled intravascular albumin. The fractional synthesis rate is considerably higher in juvenile animals (55% per day) than in adult rats (20% per day). After approximately 12 weeks of age, the fractional synthesis rate remains extremely constant in spite of continued slow growth of the lung. It is apparent from these data that in both young and adult rats the bulk of total protein synthesis is devoted to rapidly turning over proteins and that less than 4 percent of newly made protein is committed to tissue growth

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

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Ronaldo Lopes Torres

2014-06-01

Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue.

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Jin, Xiaoguang; Dai, Huaping; Ding, Ke; Xu, Xuefeng; Pang, Baosen; Wang, Chen

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic. There is no effective therapy except for lung transplantation. Rapamycin is an immunosuppressive drug with potent antifibrotic activity. The purpose of this study was to examine the effects of rapamycin on bleomycin-induced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model. Rapamycin was given at a dose of 0.5 mg/kg per gavage, beginning one day before bleomycin instillation and once daily until animal sacrifice. Ten rats in each group were sacrificed at 3, 7, 14, 28 and 56 days after bleomycin administration. Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System. Type I and III collagen fibers were identified by Picro-sirius-polarization. Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay, MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin. Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days. The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P pulmonary fibrosis, which is associated with decreased expression of MMP-9 and TIMP-1.

[Correlation between EGLN1 gene, protein express in lung tissue of rats and pulmonary artery pressure at different altitude].

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Li, S H; Li, S; Sun, L; Bai, Z Z; Yang, Q Y; Ga, Q; Jin, G E

2016-08-23

To investigate the correlation between pulmonary artery pressure (PAP) and the expression level of Egl nine homologue 1 (EGLN1) gene or its protein in lung tissue of rats at different altitudes. Totally 121 male Wistar rats were randomly divided into low altitude group (n=11), moderate altitude group and high altitude group, the rats in moderate altitude and high altitude group were further divided into 1(st) day, 3(rd) days, 7(th) days, 15(th) day and 30(th) day group according to the exposure time to hypoxic environment, each group 11 rats. The low altitude group, the PAP of rats were determined by physiological signal acquisition system, and tissue samples were collected in liquid nitrogen container for storage at an altitude of 498 m area. Moderate altitude group rats were placed in altitude of 2 260 meters of natural environment, 5 high altitude groups rats were placed in the hypobaric hypoxic chamber, simulating altitude of 4 500 meters. The PAP of rats in moderate altitude group and high altitude group were also determined by physiological signal acquisition system, and tissue samples were collected when rats were exposed to hypoxia at 1(st), 3(rd), 7(th), 15(th) and 30(th) day; Western blot was used to determine expression levels of EGLN1 protein, and person correlation analysis was used to analyze whether the protein was related to the formation of pulmonary arterial hypertension (PH) under hypoxia. Real-time quantitive PCR method determined expression levels of EGLN1 mRNA in lung tissues, and the relative expression method was used to analyze PCR data, and finally assess whether the EGLN1 gene was the initial cause of the formation of PH during hypoxia. The mean PAP of rats was (20.0±3.2) mmHg (1 mmHg=0.133 kPa) in low altitude group; in moderate altitude group, mean PAP began to increase slightly when rats were exposed to hypoxia on the 15(th) day and reached at (22.7±4.1) mmHg on hypoxic 30(th) day, but compared with the low altitude group, there was

Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

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Zhang, Ye; Feiveson, Alan H.; Lam, Chiu-Wing; Kidane, Yared H.; Ploutz-Snyder Robert; Yeshitla, Samrawit; Zalesak, Selina M.; Scully, Robert R.; Wu, Honglu; James, John T.

2014-01-01

The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust-induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust-induced toxicity to humans on earth.

[Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models].

Science.gov (United States)

Li, X Y; Zhang, X J; Zhao, J H; Xu, J Y

2016-12-12

Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months.Then the rats were sacrificed and the serum and lung tissue were prepared. The levels of 4-HNE, Trx and TrxR in peripheral blood were quantitatively analyzed by enzyme-linked immunosorbent assay(ELISA), and the activities of Trx and TrxR were measured by chemical methods. Results: Compared with the normal group, the lung tissue had more apparent emphysema in the emaciation and the fat groups under light microscope, and more inflammatory cell infiltration in alveolar septum was observed in the fat group.The levels of 4-HNE in the fat group[(24.7±8.7)mg/L]was significantly higher than that in the normal group[(15.4±4.7)mg/L, P 0.05)in the levels of 4-HNE between the emaciation and the normal groups. The levels of TrxR in the emaciation group[(7.7±1.4)μg/ml]was significantly higher than that in the normal and the fat groups[(6.2±1.1), (4.9±1.4)μg/ml, all P 0.05). The activity of Trx in the emaciation group[(32.4±8.5)×10 -3 A ·min -1 ·mg -1 ]was significantly higher than that in the normal group[(19.6±3.3)×10 -3 A ·min -1 ·mg -1 ]and the fat group[(11.3±7.5)×10 -3 A ·min -1 ·mg -1 , all P 0.05). Conclusion: Both high BMI and low BMI can affect the oxidative stress of the body, resulting in increased oxidants and decreased antioxidants, and can cause damage to the lung tissue in the rat models.

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.

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

International Nuclear Information System (INIS)

Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2014-01-01

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

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Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

2014-08-15

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

Asthmatic inflammatory reaction in the lung tissues of juvenile rats following exposure to cyolane pesticide

International Nuclear Information System (INIS)

Nour el din, A.M.; Hassanin, M.M.

2004-01-01

The present study was carried out to evaluate the effect of the organophosphorus pesticide cyolane on the tissues of the respiratory system and the pro-inflammatory markers in the serum.The study was carried out on thirty juvenile Sprague Dawley rats. Animals were divided into three groups, one used as control and the other two groups, (Gr.I and Gr.Il) received daily diet contained cyolane equivalent to 1.0 mg/kg b.wt. for 2 and 4 weeks, respectively.Nitric oxide (No), immunoglobulins E(IgE) and G (IgG) were measured in the serum of control and treated rats as an important pro-inflammatory markers.The results revealed that nitric oxide was highly significantly increased in Gr.II (P< 0.001) and significantly increased in Gr.I (P< 0.01).As regards to serum immunoglobulins, the data obtained revealed significant increase in serum total IgE in both treated groups. The IgG, as an anaphylactic antibody, showed significant increase in both groups.Histopathological examination of lung tissue revealed increased inflammatory cells infiltration and congested blood vessels in Gr.I while Gr.II showed massive inflammatory cells infiltration and congestion of blood vessels which became more pronounced. In addition, the hypertrophied muscle fibers were increased in the sub-bronchial epithelium.We concluded that young adolescents and children must advised to avoid exposure to organophosphorus pesticides, even for short time, to prevent asthmatic inflammatory reaction, which by time destroy their lung tissues. Also, the study recommended importance of measuring No, IgE and IgG serum levels as inflammatory markers for early diagnosis and management of asthma

Comparative microscopic study of human and rat lungs after overexposure to welding fume.

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Antonini, James M; Roberts, Jenny R; Schwegler-Berry, Diane; Mercer, Robert R

2013-11-01

Welding is a common industrial process used to join metals and generates complex aerosols of potentially hazardous metal fumes and gases. Most long-time welders experience some type of respiratory disorder during their time of employment. The use of animal models and the ability to control the welding fume exposure in toxicology studies have been helpful in developing a better understanding of how welding fumes affect health. There are no studies that have performed a side-by-side comparison of the pulmonary responses from an animal toxicology welding fume study with the lung responses associated with chronic exposure to welding fume by a career welder. In this study, post-mortem lung tissue was donated from a long-time welder with a well-characterized work background and a history of extensive welding fume exposure. To simulate a long-term welding exposure in an animal model, Sprague-Dawley rats were treated once a week for 28 weeks by intratracheal instillation with 2mg of a stainless steel, hard-surfacing welding fume. Lung tissues from the welder and the welding fume-treated rats were examined by light and electron microscopy. Pathological analysis of lung tissue collected from the welder demonstrated inflammatory cell influx and significant pulmonary injury. The poor and deteriorating lung condition observed in the welder examined in this study was likely due to exposure to very high levels of potentially toxic metal fumes and gases for a significant number of years due to work in confined spaces. The lung toxicity profile for the rats treated with welding fume was similar. For tissue samples from both the welder and treated rats, welding particle accumulations deposited and persisted in lung structures and were easily visualized using light microscopic techniques. Agglomerates of deposited welding particles mostly were observed within lung cells, particularly alveolar macrophages. Analysis of individual particles within the agglomerates showed that these

Depressed glucose utilization in lungs of BB wistar spontaneously diabetic rats

International Nuclear Information System (INIS)

Uhal, B.D.; Moxley, M.A.; Longmore, W.J.

1986-01-01

Lungs of BB wistar spontaneously diabetic rats were perfused with [ 14 C(U)]glucose in modified Krebs Ringer bicarbonate medium for 1.5 hours. Lungs from non-diabetic BB Wistar rats were perfused simultaneously and served as controls. The perfusions were terminated by rapid freezing of the tissue in liquid N 2 followed by separation of surfactant and residual lung fractions. The rates of glucose incorporation into surfactant DSPC, PG, and PE were decreased 4.7, 2.4 and 2.5-fold, respectively, in lungs of spontaneously diabetic rats when expressed as final product specific activities. The rate of glucose incorporation into residual PC was also reduced by 2.3-fold. Expressed as moles incorporated per gram wet weight of lung, incorporations into surfactant DSPC, PG and residual PC were also reduced by 4.1, 6.3 and 3.8-fold respectively. These data; (1) agree with previous studies of the lungs of streptozotocin and alloxan-diabetic rats; (2) show that the depressed glucose utilization for lipid synthesis observed previously is not due to streptozotocin or alloxan toxicity; (3) suggest that the BB Wistar rat will provide a useful model for the study of the effects of insulin-dependent diabetes on lung metabolism

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.

Science.gov (United States)

Zhou, Jing; Jiang, Liyan; Long, Xuan; Fu, Cuiping; Wang, Xiangdong; Wu, Xiaodan; Liu, Zilong; Zhu, Fen; Shi, Jindong; Li, Shanqun

2016-09-01

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on combined acid plus small non-acidified particle (CASP)-induced aspiration lung injury. Enhanced green fluorescent protein (EGFP(+) ) or EGFP(-) BMSCs or 15d-PGJ2 were injected via the tail vein into rats immediately after CASP-induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone-marrow-derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP-induced lung injury. Bone-marrow-derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor-α and Cytokine-induced neutrophil chemoattractant (CINC)-1 and the expression of p-p65 and increased the levels of interleukin-10 and 15d-PGJ2 and the expression of peroxisome proliferator-activated receptor (PPAR)-γ in the lung tissue in CASP-induced rats. Tumour necrosis factor-α stimulated BMSCs to secrete 15d-PGJ2 . A tracking experiment showed that EGFP(+) BMSCs were able to migrate to local lung tissues. Treatment with 15d-PGJ2 also significantly inhibited CASP-induced lung inflammation and the production of pro-inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC-derived 15d-PGJ2 activation of the PPAR-γ receptor, reducing the production of

[Effect of dust aerosol exposure on lung function and lung histopathology in rats].

Science.gov (United States)

Lei, Fengfeng; Wang, Xuebin; Liu, Hua; Chen, Qizhang; Ma, Hui; Dong, Zhibao; Sang, Yingzhu

2015-08-25

To investigate the effect of dust aerosol exposure on lung function and lung histopathology in rats. According to random number table method, 120 Wistar male rats were divided into untreated control group, treated control group and experimental group, with 40 rats in each group. Experimental group were exposed to the wind tunnel simulation of sandstorm for 5 hours in every day; the untreated control group were put in the standard living environment next to the wind tunnel; the treated control group were exposed to the same wind tunnel simulation of sandstorm for 5 hours in every day, and the speed of wind was the same as the experimental group, but excluding dust. At different time points, the lung function and electron microscopy were performed in all rats. The level of Dynamic Compliance (Cdyn) ((0.227 ± 0.023), (0.198 ± 0.022) ml/cmH₂O, 1 cmH₂O=0.098 kPa) and forced vital capacity (FVC) ((6.24 ± 0.29), (5.59 ± 0.19) ml) were lower in the experimental group at 90 and 120 days, as compared to the untreated control group (Cdyn: (0.266 ± 0.014), (0.265 ± 0.018) ml/cmH2O; FVC: (7.15 ± 0.23), (7.17 ± 0.20) ml) and treated control group (Cdyn: (0.269 ± 0.015), (0.264 ± 0.019) ml/cmH2O; FVC: (7.14 ± 0.19), (7.15 ± 0.21) ml) (all Plung tissues had no obvious abnormalities at 30, 60, 90 and 120 days in untreated control group and treated control group. But in the experimental group, at 30 days, the endothelial cells of alveolar type I cells were swelled and the number of alveolar type II cells were increased; at 60 days, alveolar type II cells hyperplastic, basement membrane thinned and destructed; at 90 days, the number of alveolar type II cells decreased, Lamellar body evacuation; at 120 days, a lot of collagen fiber was formed in the alveolar septa. The strong sandstorm environmental exposure to a certain period of time can cause the decline of lung function and the damage of lung histopathology in rats. Exposure time was positively correlated with the

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

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Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

2015-01-01

Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

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Gülay Kip

2015-09-01

Full Text Available Objective: Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R. Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods: Diabetes was induced with streptozotocin (55 mg/kg in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC, diabetes plus ischaemia-reperfusion (DIR, and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg; the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA levels were evaluated in the lung tissues of all rats. Results: Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively. The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively. The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT

Identification of rat lung-specific microRNAs by microRNA microarray: valuable discoveries for the facilitation of lung research

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Chintagari Narendranath

2007-01-01

Full Text Available Abstract Background An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs. These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. Results In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM and Tukey Honestly Significant Difference (HSD revealed 2 miRNAs (miR-195 and miR-200c expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis. Conclusion The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.

Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research.

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Wang, Yang; Weng, Tingting; Gou, Deming; Chen, Zhongming; Chintagari, Narendranath Reddy; Liu, Lin

2007-01-24

An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis. The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.

Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung

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Faeze Daghigh

2017-12-01

Full Text Available Objective(s: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats. Materials and Methods: Wistar female rats were assigned to four experimental groups (n=10 in each group: sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD; OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day. After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung. Results: Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P

Induction of Lipocalin2 in a Rat Model of Lung Irradiation

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Sadaf Sultan

2016-04-01

Full Text Available Previously, we showed that lipocalin2 (LCN2 serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

Boron uptake measurements in metastatic tumours in rat lung

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Bortolussi, S.; Altieri, S.; Bruschi, P.

2006-01-01

Lung carcinoma is the leading cause of cancer mortality worldwide; despite the introduction over the last few years of new therapeutic agents, very little progress has been made in terms of survival, and the overall prognosis for these patients remains poor. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely and essential. To study the possibility to apply BNCT in the cure of diffuse pulmonary tumours, we created a BNCT Lung Project in Pavia, supported by Ministry of Education, University and Research (MIUR), in which Physicists, Medical Doctors and Biologists are involved. The first steps were; 1. development of an animal model for Boron uptake measurements in healthy and tumour lung tissues; 2. evaluation of the possibility to treat patients with epithermal neutron beams (See S. Altieri et al., this Conference); 3. in-vitro study of BNCT efficacy (see A. Zonta et al.). Spatial Boron distribution by neutron radiography in lung metastases from Colon Adenocarcinoma is reported; furthermore we present preliminary results of Boron concentration measures in rat lung tissues. The measures were performed using alpha spectrometry in thin tissue samples. (author)

The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

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Uğur Koca

2013-01-01

Full Text Available In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis.

Epidermal growth factor and lung development in the offspring of the diabetic rat

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Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

2000-01-01

Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

Using bosentan to treat paraquat poisoning-induced acute lung injury in rats.

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Zhongchen Zhang

Full Text Available BACKGROUND: Paraquat poisoning is well known for causing multiple organ function failure (MODS and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning. OBJECTIVE: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat. METHOD: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning; the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day; and a control group (rats were administered intragastric physiological saline. On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1, endothelin-1 (ET-1, and hydroxyproline (HYP in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes. RESULT: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered. CONCLUSION: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs

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Stevenson Christopher S

2010-02-01

Full Text Available Abstract Background Vascular endothelial growth factor (VEGF and VEGF receptor 2 (VEGFR2-mediated survival signaling is critical to endothelial cell survival, maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously, we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However, the VEGFR2-mediated survival signaling in response to oxidants/cigarette smoke (CS is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs. Methods Adult male Sprague-Dawley rats were exposed CS for 3 days, 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt/PI3-kinase/eNOS downstream signaling in rat lungs. Results and Discussion We show that CS disrupts VEGFR2/PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad/Bcl-xl association. However, this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs, but it was not sufficient to cause lung cell death. Conclusion The rat lungs exposed to CS in acute, sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas emphysema is known to be associated with lung cell apoptosis.

Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture.

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Kuklin, Vladimir; Sovershaev, Mikhail; Andreasen, Thomas; Skogen, Vegard; Ytrehus, Kirsti; Bjertnaes, Lars

2005-01-01

We recently demonstrated that the non-selective endothelin-1 (ET-1) receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular pressure, although we could not exclude the possibility of a simultaneous decline in microvascular permeability. In the present study, our aim was to find out if tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat lungs that have been isolated and perfused 12 h after cecum ligation and puncture (CLP) or infusion of ET-1. Wistar rats (n = 42) were subjected to CLP. Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP + tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham-operated group (n = 5) underwent laparotomy without CLP. Twelve hours postoperatively, the lungs were isolated and perfused with blood from similarly treated rats that also were used to assess plasma concentration of ET-1 and protein kinase Calpha (PKCalpha) in lung tissue. Additionally, isolated blood perfused lungs from healthy rats were randomized to a control group (n = 8), an ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung preparations received papaverine 0.1 microg/kg added to the perfusate for vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were assessed. After CLP, the plasma concentration of ET-1 increased. Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary vascular pressures remained close to baseline throughout the experiments. Both CLP and injection of ET-1 caused significant changes in Kfc and CL that were prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP increased the content of PKCalpha by 50% and 70% in the cytosolic and the membrane fractions of lung tissue homogenates, respectively. Tezosentan prevented the

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy.

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Tabish, Tanveer A; Lin, Liangxu; Ali, Muhammad; Jabeen, Farhat; Ali, Muhammad; Iqbal, Rehana; Horsell, David W; Winyard, Paul G; Zhang, Shaowei

2018-06-06

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg -1 ) and high (15 mg kg -1 ) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin-eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

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

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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

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

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Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

2013-10-01

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality. Copyright © 2013 Elsevier GmbH. All rights reserved.

The influence of high iron diet on rat lung manganese absorption

International Nuclear Information System (INIS)

Thompson, Khristy; Molina, Ramon; Donaghey, Thomas; Brain, Joseph D.; Wessling-Resnick, Marianne

2006-01-01

Individuals chronically exposed to manganese are at high risk for neurotoxic effects of this metal. A primary route of exposure is through respiration, although little is known about pulmonary uptake of metals or factors that modify this process. High dietary iron levels inversely affect intestinal uptake of manganese, and a major goal of this study was to determine if dietary iron loading could increase lung non-heme iron levels and alter manganese absorption. Rats were fed a high iron (1% carbonyl iron) or control diet for 4 weeks. Lung non-heme iron levels increased ∼2-fold in rats fed the high iron diet. To determine if iron-loading affected manganese uptake, 54 Mn was administered by intratracheal (it) instillation or intravenous (iv) injection for pharmacokinetic studies. 54 Mn absorption from the lungs to the blood was lower in it-instilled rats fed the 1% carbonyl iron diet. Pharmacokinetics of iv-injected 54 Mn revealed that the isotope was cleared more rapidly from the blood of iron-loaded rats. In situ analysis of divalent metal transporter-1 (DMT1) expression in lung detected mRNA in airway epithelium and bronchus-associated lymphatic tissue (BALT). Staining of the latter was significantly reduced in rats fed the high iron diet. In situ analysis of transferrin receptor (TfR) mRNA showed staining in BALT alone. These data demonstrate that manganese absorption from the lungs to the blood can be modified by iron status and the route of administration

Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study

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Gholam Hassan Haddadi

2017-01-01

Full Text Available Reactive oxygen species (ROS are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham. G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05. Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05. Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05. HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05. Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats.

Extremely decreased release of prostaglandin E-like activity from chopped lung of ethyl linolenate-supplemented rats

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.; Fjalland, B.

1983-01-01

Three groups of weanling male rats were reared on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n-6] rats), or 2 energy% ethyl linolenate ([n-3] rats). The chop......). The chopped lung preparation was used to illustrate an in vitro prostaglandin formation. PGE-like activity was quantified on rat stomach strip. The release of PGE-like activity expressed as ng PGE-equivalent per g lung tissue (mean±SD) was 23±7,...

Glucose utilisation in the lungs of septic rats

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Hansson, L.; Jeppsson, B.; Ohlsson, T.; Sandell, A.; Valind, S.; Luts, A.; Wollmer, P.

1999-01-01

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ( 18 FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of 18 FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. 18 FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions. (orig.)

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats

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Kim, K.S.; Suh, G.J.; Kwon, W.Y.; Kwak, Y.H.; Lee, Kenneth; Lee, H.J.; Jeong, K.Y.; Lee, M.W.

2012-01-01

CONTEXT: Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. OBJECTIVE: To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. MATERIALS AND METHODS: Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. RESULTS: GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p CONCLUSION: Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

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

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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.

Microscopic dose distribution around PuO2 particles in lungs of hamsters, rats and dogs

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Diel, J.H.; Mewhinney, J.A.; Guilmette, R.A.

1982-01-01

Syrian hamsters, Fischer-344 rats and Beagle dogs inhaled monodisperse aerosols of PuO 2 and were sacrificed 1 to 16 days after exposure. The microscopic distribution of dose and tissue-at-risk around individual particles in lung was studied using autoradiographs of the lungs. The dose pattern in dogs and rats was more diffuse than in hamsters, resulting in a calculation of about twice the tumor incidence in rats and dogs as in hamsters on the basis of dose pattern using the same dose-effect model for all three species. The tumorigenic effect of inhaled insoluble PuO 2 particles depends on the species inhaling the material; Syrian hamsters are much less susceptible than are rats or dogs. It has been suggested that a difference in dose distribution resulting from differences in particle distributions in the two species may contribute to the differences in susceptibility in Syrian hamsters and rats. The role of dose distribution in lung cancer production is explored in this study by measuring microscopic dose patterns in regions surrounding single PuO 2 particles in lung. The alveolar structures of the dog and rat are different than those of the hamster. Based on these measurements, particles of PuO 2 in lung are more likely to cause lung cancer in dogs and rats than in hamsters

Detection of radiation induced lung injury in rats using dynamic hyperpolarized 129Xe magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Fox, Matthew S.; Ouriadov, Alexei; Hegarty, Elaine; Thind, Kundan; Wong, Eugene; Hope, Andrew; Santyr, Giles E.

2014-01-01

Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized 129 Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic 129 Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T Tr-tissue and T Tr-RBC ) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a 60 Co source. A separate group of six healthy age-matched rats served as a control group. Results: T Tr-tissue values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). T Tr-RBC did not show any significant changes between groups. T Tr-tissue was strongly correlated with T Tr-RBC in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post-irradiation, T Tr-tissue returned to values (35

Exercise training attenuated chronic cigarette smoking-induced up-regulation of FIZZ1/RELMα in lung of rats.

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Ma, Wan-li; Cai, Peng-cheng; Xiong, Xian-zhi; Ye, Hong

2013-02-01

FIZZ/RELM is a new gene family named "found in inflammatory zone" (FIZZ) or "resistin-like molecule" (RELM). FIZZ1/RELMα is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ1/RELMα expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsiveness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyperresponsiveness and up-regulation of FIZZ1/RELMα, rat chronic cigarette smoking model was established. The rats were treated with regular exercise training and their airway responsiveness was measured. Hematoxylin and eosin (HE) staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMα. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMα, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMα induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

Effect of remote ischemic postconditioning in inflammatory changes of the lung parenchyma of rats submitted to ischemia and reperfusion

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Rafael Cantero Dorsa

2015-09-01

Full Text Available AbstractObjective:To assess the effects of postconditioning remote in ischemia-reperfusion injury in rat lungs.Methods:Wistar rats (n=24 divided into 3 groups: GA (I/R n=8, GB (R-Po n=8, CG (control n=8, underwent ischemia for 30 minutes artery occlusion abdominal aorta, followed by reperfusion for 60 minutes. Resected lungs and performed histological analysis and classification of morphological findings in accordance with the degree of tissue injury. Statistical analysis of the mean rating of the degree of tissue injury.Results:GA (3.6, GB (1.3 and CG (1.0. (GA GB X P<0.05.Conclusion:The remote postconditioning was able to minimize the inflammatory lesion of the lung parenchyma of rats undergoing ischemia and reperfusion process.

Methanolic extract of Moringa oleifera leaf and low doses of gamma radiation alleviated amiodarone-induced lung toxicity in albino rats

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Hasan Hesham F.

2016-01-01

Full Text Available This study aimed to evaluate the effects of methanolic extract of Moringa oleifera (MO and/or low doses of gamma radiation (LDR on amiodarone (AMD-induced lung toxicity in rats. AMD administered to female albino rats (100 mg/kg body weight for 10 consecutive days. Rats received methanolic extract of MO (250 mg/kg bwt for 15 successive days and/or were exposed to whole body LDR (0.25Gy on the 1st and 10th days, up to a total dose of 0.5Gy. MO administration induced a significant decrease in serum tumor necrosis factor-alpha (TNF-α and transforming growth factor-beta (TGF-β levels as well as lactate dehydrogenase (LDH activity. Also, the content of malondialdehyde (MDA and hydroxyproline (HYP was significantly decreased in lung tissue. Furthermore, MO significantly increased reduced glutathione (GSH content in lung tissue as compared with AMD. The histopathological investigation of lung tissue revealed the appearance of interstitial pneumonia in rats treated with AMD. The oral administration of MO and/or exposure to LDR reversed the biochemical and histopathological alterations induced by AMD. It can be posited that MO and LDR might have a considerable role in the prevention of lung toxicity induced by AMD.

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

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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

Effects of emissions from sugar cane burning on the trachea and lungs of Wistar rats

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Verena Sampaio Barbosa Matos

Full Text Available ABSTRACT Objective: To evaluate the effects of exposure to emissions from sugar cane burning on inflammatory mechanisms in tissues of the trachea and lung parenchyma in Wistar rats after different periods of exposure. Methods: This was an experimental open randomized study. The animals were divided into four groups: a control group (CG underwent standard laboratory conditions, and three experimental groups were exposed to emissions from sugar cane burning over different periods of time, in days-1 (EG1, 7 (EG7, and 21 (EG21. After euthanasia with 200 mg/kg of ketamine/xylazine, fragments of trachea and lung were collected and fixed in 10% formalin. Histological analyses were performed with H&E and picrosirius red staining. Results: No inflammatory infiltrates were found in the tissues of CG rats. The histological examination of tissues of the trachea and lung parenchyma revealed that the inflammatory process was significantly more intense in EG7 than in the CG (p < 0.05 and p < 0.01, respectively. In comparison with the CG and EG1, angiogenesis in the lung parenchyma and collagen deposition in tracheal tissues were significantly greater only in EG21 (p < 0.001 and p < 0.01, respectively. Conclusions: In this sample, emissions from sugar cane burning induced acute focal and diffuse inflammation in the lamina propria of tracheal tissues, with no loss of ciliated epithelial tissue. In the lung parenchyma of the animals in the experimental groups, there was interstitial and alveolar edema, together with polymorphonuclear cell infiltrates.

Clearance of Free Silica in Rat Lungs by Spraying with Chinese Herbal Kombucha

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Nai-fang Fu

2013-01-01

Full Text Available The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals’ lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Clearance of free silica in rat lungs by spraying with chinese herbal kombucha.

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Fu, Nai-Fang; Luo, Chang-Hui; Wu, Jun-Cai; Zheng, Yan-Yan; Gan, Yong-Jin; Ling, Jian-An; Liang, Heng-Qiu; Liang, Dan-Yu; Xie, Jing; Chen, Xiao-Qin; Li, Xian-Jun; Pan, Rui-Hui; Chen, Zuo-Xing; Jiang, Sheng-Jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Ultrastructural changes in lung tissue after acute lead intoxication in the rat.

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Kaczynska, Katarzyna; Walski, Michał; Szereda-Przestaszewska, Małgorzata

2011-01-01

Pulmonary toxicity of lead was studied in rats after an intraperitoneal administration of lead acetate at a dose of 25 mg/kg. Three consecutive days of treatment increased lead content in the whole blood to 2.1 µg/dl and in lung homogenate it attained 9.62 µg/g w.w. versus control values of 0.17 µg/dl and 0.78 µg/g w.w., respectively. At the ultrastructural level, the effects of lead toxicity were observed in lung capillaries, interstitium, epithelial cells and alveolar lining layer. Accumulation of aggregated platelets, leucocytic elements and monocytes was found within capillaries. Interstitium comprised a substantial number of collagen, elastin filaments and lipofibroblasts. Lamellar bodies of type II pneumocytes contained phospolipid lamellae, which stratified into an irregular arrangement. Pulmonary alveoli were filled with macrophages. The extracellular lining layer of lung alveoli was partially destroyed. This study provided evidence that acute lead intoxication affects the whole lung parenchyma and by impairing production of the surfactant might disturb the regular respiratory function.

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

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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.)

Effects of FTY720 on Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats

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Liangrong Wang

2017-01-01

Full Text Available Background. Sphingosine-1-phosphate (S1P is a biologically active lysophospholipid mediator involved in modulating inflammatory process. We investigated the effects of FTY720, a structural analogue of S1P after phosphorylation, on lung injury induced by hindlimb ischemia reperfusion (IR in rats. Methods. Fifty Sprague-Dawley rats were divided into groups SM, IR, F3, F5, and F10. Group SM received sham operation, and bilateral hindlimb IR was established in group IR. The rats in groups F3, F5, and F10 were pretreated with 3, 5, and 10 mg/kg/d FTY720 for 7 days before IR. S1P lyase (S1PL, sphingosine kinase (SphK 1, and SphK2 mRNA expressions, wet/dry weight (W/D, and polymorphonuclear/alveolus (P/A in lung tissues were detected, and the lung injury score was evaluated. Results. W/D, P/A, and mRNA expressions of S1PL, SphK1, and SphK2 were higher in group IR than in group SM, while these were decreased in both groups F5 and F10 as compared to IR (p<0.05. The lung tissue presented severe lesions in group IR, which were attenuated in groups F5 and F10 with lower lung injury scores than in group IR (p<0.05. Conclusions. FTY720 pretreatment could attenuate lung injury induced by hindlimb IR by modulating S1P metabolism and decreasing pulmonary neutrophil infiltration.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

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Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P reversal of lung function decline (all P reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

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Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

2014-01-01

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

Effect of connective tissue growth factor (CTGF) expression on radiation pulmonary fibrosis in rats

International Nuclear Information System (INIS)

Huang Shanying; Song Liangwen; Zhang Yong; Sun Li; Li Yang

2005-01-01

Objective: To explore the effect of connective tissue growth factor (CTGF) on initiation of radiation pulmonary fibrosis (RPF) and the relation to α-smooth muscle actin (α-SMA). Methods: The promotive effect of CTGF on proliferation of human lung fibroblasts (HLF) by 5 Gy of 60 Co γ-rays was determined by MTT colorimetry. The expressions of CTGF and α-SMA in HLF were observed by Western blot. Changes of collagen I and III in rat lungs were determined by Sirius red staining and polarization microscopy. Expressions of CTGF and α-SMA in RPF were observed with immunohisto-chemistry and analysis. Results: Expressions of CTGF and α-SMA were increased. CTGF reached its peak at 24 h after irradiation, whereas α-SMA still kept at a high level 72 h after irradiation. A small amount of collagen was produced in rat lung one month after irradiation, in which type III collagen was the primary component. However, a large amount of collagen was produced in rat lung 3-6 months after irradiation, in which type I was dominant. CTGF began to expression 1 week after irradiation in proliferative fibroblasts of rat lung, and it was most evident 3 months after irradiation. α-SMA began to express in proliferative myofibroblasts 1 week after irradiation, and the high peek was reached at 3 months after irradiation. Conclusion: Irradiation can induce expression of CTGF in pulmonary tissue and the later can promote the transformation of fibroblasts to myofibroblasts, strengthen the ability of synthesis and secretion of type I and III collagen. (authors)

Identification of rat lung-specific microRNAs by microRNA microarray: valuable discoveries for the facilitation of lung research

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Chintagari Narendranath; Chen Zhongming; Gou Deming; Weng Tingting; Wang Yang; Liu Lin

2007-01-01

Abstract Background An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. Results In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to d...

Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

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Li Jianjun

2012-09-01

Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

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Hasan Kahraman

2013-03-01

Full Text Available Objective: Methotrexate (MTX is known to have deleterious side effects on lung tissue. We aimed to investigate the effects of erythropoietin (EPO and N-acetyl-cysteine (NAC on MTX-induced lung injury in rats. Study Design: Animal experiment. Material and Methods: Twenty-six female Sprague-Dawley rats were divided into 4 groups. Sham group, 0.3 mL saline; MTX group, 5 mg/kg MTX; EPO group, 5mg/kg MTX and 2000 IU/kg EPO; NAC group, 5 mg/kg MTX and 200 mg/kg NAC were administered once daily for 4 consecutive days. Malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT and inflammation and congestion scores in lung tissues were evaluated. Results: In MTX group MDA were significantly higher, CAT and SOD were significantly lower than in sham, EPO and NAC groups (p0.005. In group MTX both scores were significantly higher than in sham (p<0.005. The congestion score of group MTX was significantly higher than those of group EPO and NAC (p<0.005. Conclusion: EPO and NAC have significant preventive effects on MTX-induced lung injury in rats. Decreased antioxidant capacity and increased MDA level may cause the oxidative damage in MTX group. Also, higher antioxidant capacity and lower MDA level may be a response to oxidative stress in EPO and NAC groups.

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats.

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Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao; Zeng, Zhenling

2015-01-01

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC00∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

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Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

2016-01-01

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

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Xue-Yuan Chen

Full Text Available OBJECTIVE: Acute lung injury (ALI, is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM-loaded immunoliposome (NLP functionalized with pulmonary surfactant protein A (SP-A antibody (SPA-DXM-NLP in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

Formation of cigarette smoke-induced DNA adducts in the rat lung and nasal mucosa

International Nuclear Information System (INIS)

Gupta, R.C.; Sopori, M.L.; Gairola, C.G.

1989-01-01

The formation of DNA adducts in the nasal, lung, and liver tissues of rats exposed daily to fresh smoke from a University of Kentucky reference cigarette (2R1) for up to 40 weeks was examined. The amount of smoke total particulate matter (TPM) inhaled and the blood carboxyhemoglobin (COHb) values averaged 5-5.5 mg smoke TPM/day/rat and 5.5%, respectively. The pulmonary AHH activity measured at the termination of each experiment showed an average increase of about two- to threefold in smoke-exposed groups. These observations suggested that animals effectively inhaled both gaseous and particulate phase constituents of cigarette smoke. DNAs from nasal, lung, and liver tissue were extracted and analyzed by an improved 32 P-postlabeling procedure. The data demonstrate the DNA-damaging potential of long term fresh cigarette smoke exposure and suggest the ability of the tissue to partially recover from such damage following cessation of the exposure

Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Fox, Matthew S. [Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Ouriadov, Alexei; Hegarty, Elaine [Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Thind, Kundan [Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Wong, Eugene [Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and London Regional Cancer Program, London, Ontario, N6C 2R6 (Canada); Hope, Andrew [Department of Radiation Oncology, University of Toronto, Toronto, Ontario, M5S 3E2, Canada and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, M5T 2M9 (Canada); Santyr, Giles E., E-mail: gsantyr@robarts.ca [Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada); Department of Medical Imaging, Western University, London, Ontario, N6A 5B7 (Canada)

2014-07-15

Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized{sup 129}Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-tissue} values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-RBC} in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

Science.gov (United States)

Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

Characterization of rat lung ICAM-1

DEFF Research Database (Denmark)

Beck-Schimmer, B; Schimmer, R C; Schmal, H

1998-01-01

studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...... peaked at 4 h, while lung ICAM- I protein peaked at 6 h. CONCLUSIONS: Quantitation of ICAM-1 expression in vitro and in vivo suggests that ICAM-1 plays a central role in two lung inflammatory models. Furthermore, lung ICAM-1 upregulation involves at least two cell types: vascular endothelial cells...

Evaluation of oxidative response and tissular damage in rat lungs exposed to silica-coated gold nanoparticles under static magnetic fields

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Ferchichi S

2016-06-01

Full Text Available Soumaya Ferchichi,1 Hamdi Trabelsi,1 Inès Azzouz,1 Amel Hanini,2 Ahmed Rejeb,3 Olfa Tebourbi,1 Mohsen Sakly,1 Hafedh Abdelmelek1 1Laboratory of Integrative Physiology, Faculty Of Sciences of Bizerte, 2Laboratory of Vascular Pathology, Carthage University, Carthage 3Laboratory of Pathological Anatomy, National School of Veterinary Medicine of Sidi Thabet, Manouba Univeristy, Manouba, Tunisia Abstract: The purpose of our study was the evaluation of toxicological effects of silica-coated gold nanoparticles (GNPs and static magnetic fields (SMFs; 128 mT exposure in rat lungs. Animals received a single injection of GNPs (1,100 µg/kg, 100 nm, intraperitoneally and were exposed to SMFs, over 14 days (1 h/day. Results showed that GNPs treatment induced a hyperplasia of bronchus-associated lymphoid tissue. Fluorescence microscopy images showed that red fluorescence signal was detected in rat lungs after 2 weeks from the single injection of GNPs. Oxidative response study showed that GNPs exposure increased malondialdehyde level and decreased CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in rat lungs. Furthermore, the histopathological study showed that combined effects of GNPs and SMFs led to more tissular damages in rat lungs in comparison with GNPs-treated rats. Interestingly, intensity of red fluorescence signal was enhanced after exposure to SMFs indicating a higher accumulation of GNPs in rat lungs under magnetic environment. Moreover, rats coexposed to GNPs and SMFs showed an increased malondialdehyde level, a fall of CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in comparison with GNPs-treated group. Hence, SMFs exposure increased the accumulation of GNPs in rat lungs and led to more toxic effects of these nanocomplexes. Keywords: malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, bronchus-associated lymphoid tissue, nanotoxicity, histopathological study

Lung tissue mechanics as an emergent phenomenon.

Science.gov (United States)

Suki, Béla; Bates, Jason H T

2011-04-01

The mechanical properties of lung parenchymal tissue are both elastic and dissipative, as well as being highly nonlinear. These properties cannot be fully understood, however, in terms of the individual constituents of the tissue. Rather, the mechanical behavior of lung tissue emerges as a macroscopic phenomenon from the interactions of its microscopic components in a way that is neither intuitive nor easily understood. In this review, we first consider the quasi-static mechanical behavior of lung tissue and discuss computational models that show how smooth nonlinear stress-strain behavior can arise through a percolation-like process in which the sequential recruitment of collagen fibers with increasing strain causes them to progressively take over the load-bearing role from elastin. We also show how the concept of percolation can be used to link the pathologic progression of parenchymal disease at the micro scale to physiological symptoms at the macro scale. We then examine the dynamic mechanical behavior of lung tissue, which invokes the notion of tissue resistance. Although usually modeled phenomenologically in terms of collections of springs and dashpots, lung tissue viscoelasticity again can be seen to reflect various types of complex dynamic interactions at the molecular level. Finally, we discuss the inevitability of why lung tissue mechanics need to be complex.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

Science.gov (United States)

Wan, Mei-Hua; Li, Juan; Tang, Wen-Fu; Gong, Han-Lin; Chen, Guang-Yuan; Xue, Ping; Zhao, Xian-Lin; Xia, Qing

2011-09-01

To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P 0.05). Only two rats in the ANP group died. DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

Volume-Dependent Expression of In-Field and Out-of-Field Effects in the Proton-Irradiated Rat Lung

NARCIS (Netherlands)

Coppes, Robert P.; Muijs, Christina T.; Faber, Hette; Gross, Sascha; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; van Luijk, Peter

2011-01-01

Purpose: To investigate whether occurance of early radiation effects in lung tissue depends on local close only. Methods and Materials: Twenty-five percent. 50%, 66%, 88%, or 100% of the rat lung was irradiated using single fractions of 150-MeV protons. For all volumes, in-field and out-of-field

LYCOPENE EFFICIENCY IN THE MODULATION OF OXIDATIVE DAMAGE IN DIFFERENT TISSUES OF GAMMA IRRADIATED RATS

International Nuclear Information System (INIS)

EL-TAHAWY, N.A.; NADA, A.S.; REZK, R.G.

2008-01-01

Exposure to ionizing radiation induces oxidative stress that has been recognized as an important etiological factor in the causation of several chronic diseases. Lycopene, a carotenoid almost exclusively present in tomatoes and tomatoes products, is a lipid soluble antioxidant claimed to possess cardio protective and anticancer properties. The present study was designed to determine the possible modulator effects of lycopene on radiation-induced oxidative damage to liver, spleen and lung tissues. Animals were supplemented with lycopene (5 mg/kg body weight/ day) by gavages for two weeks before whole body exposure to gamma rays and within the period of irradiation (3 successive doses, each of 3 Gy at 72 hours intervals). Animals were sacrificed on the 3 r d day post the last irradiation session.The results obtained in the present study showed that whole body gamma irradiation produced oxidative stress manifested by significant elevation in lipid peroxides levels measured as thiobarbituric acid reactive substances (TBARS) associated with significant decrease of nitric oxide (NO) content. Non-significant change in total cupper (Cu) in the three tissues was recorded while significant increase of total iron (Fe) was observed in liver and spleen tissues only. Liver tissue of irradiated rats showed significant decrease in the activities of the antioxidant enzymes as superoxide dismutase (SOD) and catalase (CAT). In spleen tissues, there was a significant increase of SOD and significant decrease of CAT activities while in lung tissues, both SOD and CAT activities showed significant increase.Histological observations of photomicrograph of liver sections showed that radiation-induced sever damage obvious by dilated portal vein, ruptured hepatocytes, necrotic, pyknotic, karyolitic nuclei and vacuolated cytoplasm. In spleen tissue, radiation was induced degeneration of lymphatic nodules, dilation follicular artery and marked hemorrhage. In lung tissue, radiation- induces ill

An experimental two-stage rat model of lung carcinoma initiated by radon exposure

International Nuclear Information System (INIS)

Poncy, J.L.; Laroque, P.; Fritsch, P.; Monchaux, G.; Masse, R.; Chameaud, J.

1992-01-01

We present the results of a two-stage biological model of lung carcinogenesis in rats. The histogenesis of these tumors was examined, and DNA content of lung cells was measured by flow cytometry during the evolving neoplastic stage. Tumors were induced in rat lungs after radon inhalation (1600 WLM) followed by a promoter treatment; six intramuscular injections of 5,6-benzoflavone (25 mg/kg of body weight/injection) every 2 wk. Less than 3 mo after the first injection of benzoflavone, squamous cell carcinoma was observed in the lungs of all rats exposed to radon. The preneoplastic lesions gradually developed as follows: hyperplastic bronchiolar-type cells migrated to the alveoli from cells that proliferated in bronchioles and alveolar ducts; initial lesions were observed in almost all respiratory bronchioles. From some hyperplasias, epidermoid metaplasias arose distally, forming nodular epidermoid lesions in alveoli, which progressed to form squamous papilloma and, finally, epidermoid carcinomas. The histogenesis of these experimentally induced epidermoid carcinomas showed the bronchioloalveolar origin of the tumor. This factor must be considered when comparing these with human lesions; in humans, lung epidermoid carcinomas are thought to arise mainly in the first bronchial generations. The labeling index of pulmonary tissue after incorporation of 3 H-thymidine by the cells was 0.2% in control rats. This index reached a value of 1 to 2% in the hyperplastic area of the bronchioles and 10 to 15% in epidermoid nodules and epidermoid tumors, respectively. DNA cytometric analysis was performed on cell suspensions obtained after enzymatic treatment of paraffin sections of lungs from rats sacrificed during different stags of neoplastic transformations. Data showed the early appearance of a triploid cell population that grew during the evolution of nodular epidermoid lesions to epidermoid carcinomas

Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

International Nuclear Information System (INIS)

Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo; Suda, Syuichi; Fukuzaki, Minoru.

1994-01-01

We investigated the nuclear magnetic resonance (NMR) relaxation times, T 1 and T 2 , for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T 1 and T 2 for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T 1 and T 2 between adenocarcinoma and lung tissue. The values of T 1 and T 2 for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T 1 and T 2 are not specific to malignant tissues. (author)

Effects of quorum sensing system lasR/rhlR gene on the expression of Foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection

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Qing-qing XIANG

2016-03-01

Full Text Available Objective 　To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer wild strain (PAO1 and quorum sensing (QS deficient strain (ΔlasRΔrhlR. Methods 　Twenty-one SD rats were randomly assigned into 3 groups (7 each: ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF, TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results 　The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10 400.00±6313.70/g lung tissue than that in ΔlasRΔrhlR group (975.00±559.97/g lung tissue, P<0.05. There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65±0.32, and it was significantly higher in PAO1 group (4.62±1.07 than in ΔlasRΔrhlR group (2.15±1.43, P<0.05. The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66±1412.95, and significantly higher in PAO1 group (65 090.56±33

Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.

Science.gov (United States)

Dollery, C T; Junod, A F

1976-01-01

1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation. PMID:1276542

The First Korean Case of Cutaneous Lung Tissue Heterotopia

Science.gov (United States)

Jeon, Ga Won; Han, Seong Woo; Jung, Ji Mi; Kang, Mi Seon

2010-01-01

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea. PMID:20808688

Histomorphologic change of radiation pneumonitis in rat lungs: captopril reduces rat lung injury induced by irradiation

International Nuclear Information System (INIS)

Kim, Jin Hee

1999-01-01

To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-α and TGF β and rat lung damage by radiation and captopril. Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group expression of TNF-α and TGF-β] increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF- P increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation alone group. It

Melatonin attenuates lung injury in a hind limb ischemia–reperfusion rat model

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Hamed Takhtfooladi

2015-01-01

Full Text Available Objective: This study evaluated the protective antioxidant effect of melatonin on lung injury as a remote organ after skeletal muscle ischemia–reperfusion in rats. Methods: Thirty male Wistar rats were allocated randomly into three experimental groups: operated with no ischemia (Sham group, ischemia–reperfusion group and ischemia–reperfusion + melatonin group. Hind limb ischemia was induced by clamping the femoral artery. After 2 h ischemia, the clamp was removed and the animal underwent 24 h reperfusion. Rats in the ischemia–reperfusion + melatonin group received melatonin (10 mg/kg i.v., immediately before the clamp was removed. At the end of the trial, animals were euthanized and the lungs were removed for water content determination, histopathological and biochemical studies. Results: In the ischemia–reperfusion + melatonin group, tissues showed less intense histological abnormalities such as neutrophilic infiltration, intra-alveolar hemorrhage and edema compared with the ischemia–reperfusion group. Histopathologically, there was a significant difference (P < 0.05 between the two groups. The lung water content in the ischemia–reperfusion + melatonin group was significantly lower than the ischemia–reperfusion group (P < 0.05. Lung tissue myeloperoxidase (MPO activity and nitric oxide (NO level were significantly (P < 0.05 increased by ischemia–reperfusion. The increase in these parameters was reduced by melatonin.Comparing the ischemia–reperfusion + melatonin group with the sham group, no significant increase in all analyzed aspects of the research was observed. Conclusions: These findings suggest that melatonin has preventive effects in lung tissue injury after transient femoral artery occlusion. Keywords: Melatonin, Ischemia–reperfusion, Lung remote injury, Histopathology, Myeloperoxidase, Nitric oxide

Riboflavin attenuates lipopolysaccharide-induced lung injury in rats.

Science.gov (United States)

Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Korashy, Hesham M; Sayed-Ahmed, Mohammed M; Hafez, Mohamed M; Al-Shabanah, Othman A; Nagi, Mahmoud N; Bahashwan, Saleh

2015-01-01

Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p riboflavin significantly (p riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.

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)

Pistacia chinensis: A Potent Ameliorator of CCl4 Induced Lung and Thyroid Toxicity in Rat Model

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Kiran Naz

2014-01-01

Full Text Available In the current study protective effect of ethanol extract of Pistacia chinensis bark (PCEB was investigated in rats against CCl4 induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, γ-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4 treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3 and T4 content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4 were restored to normal level with PCEB treatment. Histological study of CCl4 treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4 treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion, P. chinensis exhibited antioxidant activity by the presence of free radical quenching constituents.

Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats

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Sikdar Sourav

2014-06-01

Full Text Available Objectives:Condurango is widely used in various systems of complementary and alternative medicines (CAM against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods:Fifteen male and 15 female Sprague-Dawley (SD rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate reactive oxygen species (ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion:The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional

Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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Chung-Kan Peng

Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

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Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin

2014-01-01

Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict

Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

International Nuclear Information System (INIS)

Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

2003-01-01

Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation

Protective effects of ghrelin in ventilator-induced lung injury in rats.

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Li, Guang; Liu, Jiao; Xia, Wen-Fang; Zhou, Chen-Liang; Lv, Li-Qiong

2017-11-01

Ghrelin has exhibited potent anti-inflammatory effects on various inflammatory diseases. The aim of this study was to investigate the potential effects of ghrelin on a model of ventilator-induced lung injury (VILI) established in rats. Male Sprague-Dawley rats were randomly divided into three groups: low volume ventilation (LV, Vt=8ml/kg) group, a VILI group (Vt=30ml/kg), and a VILI group pretreated with ghrelin (GH+VILI). For the LV group, for the VILI and GH+VILI groups, the same parameters were applied except the tidal volume was increased to 40ml/kg. After 4h of MV, blood gas, lung elastance, and levels of inflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and (MIP)-2 and total protein in bronchoalveolar lavage fluid (BALF) were analyzed. Myeloperoxidase (MPO), (TLR)-4, and NF-κB, were detected in lung tissues. Water content (wet-to-dry ratio) and lung morphology were also evaluated. The VILI group had a higher acute lung injury (ALI) score, wet weight to dry ratio, MPO activity, and concentrations of inflammatory mediators (TNF-α, IL-6, IL-1β, and MIP-2) in BALF, as well as higher levels of TLR4 and NF-κB expression than the LV group (Pghrelin pretreatment (PGhrelin pretreatment also decreased TLR4 expression and NF-κB activity compared with the VILI group (PGhrelin pretreatment attenuated VILI in rats by reducing MV-induced pulmonary inflammation and might represent a novel therapeutic candidate for protection against VILI. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of gamma radiation on tissue elastin content and serum elastolytic activity in rats

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Drozdz, M.; Olczyk, K.; Piwowarczyk, B.; Stawiarska, B.

1981-01-01

The elastin content of aorta, heart, skin and lungs as well as the serum elastolytic activity were determined in rats exposed to radiation. It was found that a single irradiation of rats with gamma rays (500 r) caused a decrease of the elastin content in all examined tissues. The serum elastolytic activity in the irradiated rats was increased. It is suggested that elastin degradation following radiation may be caused by changes in its molecular structure and possibly, due to increased serum elastolytic activity. (author)

Lung, aorta, and platelet metabolism of 14C-arachidonic acid in vitamin E deficient rats

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Valentovic, M.A.; Gairola, C.; Lubawy, W.C.

1982-01-01

14 C-arachidonic acid metabolism was determined in aortas, platelets, and perfused lungs from rats pair fed a basal diet supplemented with 0 or 100 ppm vitamin E for 11 weeks. Spontaneous erythrocyte hemolysis tests showed 92% and 8% hemolysis for the 0 and 100 ppm vitamin E groups, respectively. Elevated lung homogenate levels of malonaldehyde in the 0 ppm group confirmed its deficient vitamin E status. Aortas from the vitamin E deficient group synthesized 54% less prostacyclin than aortas from the supplemented group (p less than 0.05). Although thromboxane generation by platelets from the vitamin E deficient group exhibited a 37% increase, this difference was not statistically significant compared to the supplemented animals. Greater amounts of PGE2, PGF2 alpha, TXB2, and 6-keto-PGF1 alpha were obtained in albumin buffer perfusates from lungs of vitamin E deficient rats than in those from supplemented rats. Significant differences (p less than 0.05) were noticed, however, only for PGE2 and PGF2 alpha. These studies indicate that vitamin E quantitatively alters arachidonic acid metabolism in aortic and lung tissue but its effect on thromboxane synthesis by platelets is less marked

Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

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Ailan Zhang

Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

Tissue distribution of 14C-diazepam and its metabolites in rats

International Nuclear Information System (INIS)

Igari, Y.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.

1982-01-01

We have kinetically investigated the tissue distribution of 14 C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of 14 C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence

Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

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Zeliha Selamoglu-Talas

2015-10-01

Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

The influence of dietary Cu and diabetes on tissue 67Cu retention kinetics in rats

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Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L.

1991-01-01

Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 μCi 67 Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on 67 Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained 67 Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained 67 Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained 67 Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of 67 Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of 67 Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted

Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model.

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Zemmouri, Hanene; Sekiou, Omar; Ammar, Sonda; El Feki, Abdelfattah; Bouaziz, Mohamed; Messarah, Mahfoud; Boumendjel, Amel

2017-12-01

To find bioactive medicinal herbs exerting anti-asthmatic activity, we investigated the effect of an aqueous extract of Urtica dioica L. (Urticaceae) leaves (UD), the closest extract to the Algerian traditional use. In this study, we investigated the in vivo anti-asthmatic and antioxidant activities of nettle extract. Adult male Wistar rats were divided into four groups: Group I: negative control; group II: Ovalbumin sensitized/challenged rats (positive control); group III: received UD extract (1.5 g/kg/day) orally along the experimental protocol; group IV: received UD extract (1.5 g/kg/day) orally along the experimental protocol and sensitized/challenged with ovalbumin. After 25 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. The oxidative stress parameters were evaluated in the lungs, liver and erythrocytes. Then, correlations between markers of airway inflammation and markers of oxidative stress were explored. UD extract significantly (p nettle extract was also investigated for the total phenolic content (30.79 ± 0.96 mg gallic acid/g dry extract) and shows DPPH radical scavenging activity with 152.34 ± 0.37 μg/mL IC 50 value. The results confirmed that UD administration might be responsible for the protective effects of this extract against airway inflammation.

Angiotensin-(1?7) inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

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Lu, W.; Kang, J.; Hu, K.; Tang, S.; Zhou, X.; Yu, S.; Li, Y.; Xu, L.

2016-01-01

Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7)] on lung injury in rats induced by chronic intermittent hypoxia (CIH). We randomly assigned 32 male Sprague-Dawley rats (180–200 g) to normoxia control (NC), CIH-untreated (uCIH), Ang-(1–7)-treated normoxia control (N-A), and Ang-(1–7)-treated CIH (CIH-A) groups. Oxidative stress biomarkers were measured ...

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

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Cyril Francioli

Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

Ex vivo effects of lysine clonixinate on cyclooxygenases in rat lung and stomach preparations.

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Franchi, A M; Di Girolamo, G; De los Santos, A R; Marti, M L; Gimeno, M A

1999-01-01

Lysine clonixinate (LC) is an anti-inflammatory, anti-pyretic and analgesic drug with minor digestive side effects, which might suggest a weak COX-1 inhibitor. The aim of this study focused on ex vivo effects of LC 40 mg/kg ip and indomethacin (INDO) 10 mg/kg ip in lung and stomach preparations of control rats and LPS-treated rats (5 mg/kg ip). The non-steroidal antiinflammatory drugs were administered concomitantly, following three hours and before one, two or three hours of LPS treatment. Tissues were weighed and incubated in 2 ml of Kress Ringer Bicarbonate buffer containing glucose (11 mM) under an atmosphere of 95% oxygen and 5% CO(2). Approximately 200 mg of tissue were used for each determination; 0.25 microCi of (14)C-arachidonic acid was added to each tube and the tissues were incubated for 60 min. Prostanoids were extracted from the incubation medium and separated by TLC. Results were expressed as a percentage of the total radioactivity of the plates (% of cpm on plate/100 mg ww). It was found that LC animals that were not given LPS did not modify the synthesis of PGE(2); in lung and stomach tissues showing that did not inhibit COX-1 activity. However, LC inhibited clearly the synthesis of PGE(2) in both preparations obtained from LPS-treated animals. The inhibition was shown when the rats were treated concomitantly, 3 h after or 1 or 2 h before the injection of LPS.

Morphologic and biochemical changes in male rat lung after surgical and pharmacological castration

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M.S. Ojeda

2000-03-01

Full Text Available The morphology of the rat lung was studied by light microscopy in different situations: after surgical and pharmacological castration and after administration of testosterone to the castrated rat to determine if the androgen is required to maintain the normal morphology of the lung. We also determined the effect of flutamide on the phospholipid composition of both the surfactant and microsomes of the lung. Rats were separated into five groups: I - control non-castrated rats, II - castrated rats sacrificed 21 days after castration, III - castrated rats that received testosterone daily from day 2 to day 21 after castration, IV - castrated rats that received testosterone from day 15 to day 21 after castration, and V - control rats injected with flutamide for 7 days. The amount of different phospholipids in the surfactant and microsomes of the lung was measured in group I and V rats. At the light microscopy level, the surgical and pharmacological castration provoked alterations in the morphology of the lung, similar to that observed in human lung emphysema. The compositions of surfactant and microsomes of the lung were similar to those previously reported by us for the surgically castrated rats. These results indicate that androgens are necessary for the normal morphology as well as for some metabolic aspects of the lung.

Late biochemical changes in the rat lung after whole body irradiation

International Nuclear Information System (INIS)

Dancewicz, A.M.; Kubicka, T.

1976-01-01

Young Wistar rats were exposed to 650 R of whole body X-rays then sacrificed at different times after exposure up to one year, and various biochemical parameters in lung tissue were determined. Decrease in protein and elastin content and elevation in fibrinolytic and catheptic activity lasted during the whole observation period. In other parameters a fluctuation, mostly decrease followed by an increase, was seen only during the acute phase of radiation disease. (author)

Glutathione turnover in 14 rat tissues

International Nuclear Information System (INIS)

Potter, D.W.; Tran, T.

1990-01-01

GSH is a tripeptide found in all tissues and is important in maintaining cellular redox status. First-order rate constants for GSH turnover were determined for various tissues of Fischer male rats. Animals were administered [ 35 S]Cys by tail vein injection and GSH turnover was estimated by the decrease in GSH specific activity following incorporation of Cys, 1-102 hr after administration. Tissue nonprotein sulfhydryls (NPSH) were detected by Ellman's assay and compared with GSH and Cys concentrations determined by HPLC with electrochemical detection. [ 35 S]GSH was analyzed by HPLC equipped with a flow-through radioactivity detector. Although total GSH and Cys were usually slightly lower than NPSH concentrations for the tissues examined, both assay systems gave comparable results. An exception was the glandular stomach which had approximately 2-fold higher NPSH. Liver and kidney had rapid turnover rates with GSH half-lives between 2-5 hr, while heart and skeletal muscle tissue had half-lives of 80-90 hr. Turnover in the blood was slowest, with a half-life of 170 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach > duodenum = small intestine = caecum = large intestine = colon > forestomach. GSH half-life in lung and skin was approximately 45 hr. These studies indicate that tissues utilize GSH at markedly different rates

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.

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Schelegle, E S; Walby, W F; Mansoor, J K; Chen, A T

2001-05-01

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

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Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

2014-01-01

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

An exposure system for measuring nasal and lung uptake of vapors in rats

Energy Technology Data Exchange (ETDEWEB)

Dahl, A.R.; Brookins, L.K.; Gerde, P. [National Inst. for Working Life, Solna (Sweden)

1995-12-01

Inhaled gases and vapors often produce biological damage in the nasal cavity and lower respiratory tract. The specific site within the respirator tract at which a gas or vapor is absorbed strongly influences the tissues at risk to potential toxic effects; to predict or to explain tissue or cell specific toxicity of inhaled gases or vapors, the sites at which they are absorbed must be known. The purpose of the work reported here was to develop a system for determining nose and lung absorption of vapors in rats, an animal commonly used in inhalation toxicity studies. In summary, the exposure system described allows us to measure in the rate: (1) nasal absorption and desorption of vapors; (2) net lung uptake of vapors; and (3) the effects of changed breathing parameters on vapor uptake.

Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

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Guzel, Ahmet; Kanter, Mehmet; Guzel, Aygul; Pergel, Ahmet; Erboga, Mustafa

2012-06-01

The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications

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Gupta, Sweta K. [Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee (India); Dinda, Amit K. [Department of Pathology, All India Institute of Medical Sciences, New Delhi (India); Potdar, Pravin D. [Department of Molecular Medicine, Jaslok Hospital and Research Centre, Mumbai (India); Mishra, Narayan C., E-mail: mishrawise@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee (India)

2013-10-15

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H and E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. - Highlights: • We successfully fabricated decellularized scaffold from cadaver goat-lung tissue. • Decellularized goat-lung scaffolds were found to be highly porous. • Skin derived MSC shows high cell viability and proliferation over the scaffold. • Phenotype of MSCs was well maintained over the scaffold. • The scaffold shows potential for applications in skin tissue engineering.

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications

International Nuclear Information System (INIS)

Gupta, Sweta K.; Dinda, Amit K.; Potdar, Pravin D.; Mishra, Narayan C.

2013-01-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H and E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. - Highlights: • We successfully fabricated decellularized scaffold from cadaver goat-lung tissue. • Decellularized goat-lung scaffolds were found to be highly porous. • Skin derived MSC shows high cell viability and proliferation over the scaffold. • Phenotype of MSCs was well maintained over the scaffold. • The scaffold shows potential for applications in skin tissue engineering

Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

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Saddiq, Amna Ali; Mohamed, Azza Mostafa

2016-07-01

The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

Lung transplantation in the rat. III. Functional studies in iso- and allografts

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Marck, K.W.; Prop, J.; Wildevuur, C.R.

1983-01-01

Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research

Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

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He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

2013-01-01

A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung.

Puerarin Attenuates Ovalbumin-Induced Lung Inflammation and Hemostatic Unbalance in Rat Asthma Model

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Feng Dong

2014-01-01

Full Text Available Aim. We aimed to investigate and evaluate the preventive activity of puerarin on the ovalbumin-induced asthma rat model. Materials and Methods. Male Wistar rats were sensitized intraperitoneally on days 0, 7, and 14 and challenged to ovalbumin intratracheally on day 21. Groups of sensitized rats were treated randomly either with placebo, puerarin, dexamethasone, or puerarin combined with dexamethasone, from days 15 to 20. Inflammatory markers, including cell counts in bronchoalveolar lavage fluid (BALF, inflammatory cytokines, histopathology, and coagulation parameters, such as coagulation tests and the activity of coagulation factors, were analyzed. Results. Puerarin significantly inhibited the recruitment of inflammatory cells in BALF and lung tissue. At the same time, the release of IL-4, IL-10, and IFN-γ in serum and the expression of mRNAs in lung tissue homogenate were changed by puerarin. Administration of puerarin also effectively rectified the coagulation disorder in asthmatic rats, such as prothrombin time (PT (P<0.01, thrombin time (TT (P<0.05, fibrinogen (FIB (P<0.01,the activity of factor II (FII (P<0.01, the activity of factor V (FV (P<0.05, the activity of factor VII (FVII (P<0.05, the activity of factor X (FX (P<0.05, the activity of factor VIII (FVIII (P<0.01, the activity of factor IX (FIX (P<0.05, and the activity of factor XII (FXII (P<0.05. Conclusions. Our results provide a clue that puerarin was useful for the preventive of allergic airway disease in rodents.

[Altered expressions of alkane monooxygenase and hypoxia inducible factor-1α expression in lung tissue of rat hypoxic pulmonary hypertension].

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Deng, Hua-jun; Yuan, Ya-dong

2013-10-29

To explore the altered expressions of alkane monooxygenase (AlkB) and hypoxia-inducible factor-1α (HIF-1α) in a rat model of hypoxic pulmonary arterial hypertension. Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding. Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas. And the oxygen concentration of (10.0 ± 0.5)% was controlled by oxygen monitoring control system. The control group was maintained in room air. Both groups stayed in the same room with the same diet. After 8 weeks, the level of mean pulmonary pressure (mPAP) was measured by right-heart catheterization, right ventricular hypertrophy index (RVHI) calculated by the ratio of right ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling (HPSR) observed under microscope. And the levels of AlkB and HIF-1α mRNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. At 8 weeks post-hypoxia, compared with the control group [11.0 ± 0.7 mm Hg (1 mm Hg = 0.133 kPa), 0.210 ± 0.035], the levels of mPAP and RVHI in hypoxia group (33.3 ± 1.3 mm Hg, 0.448 ± 0.013) increased significantly (both P < 0.05), the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly (0.338 ± 0.085 vs 0.688 ± 0.020, P < 0.01) (0.483 ± 0.052 vs 0.204 ± 0.010, P < 0.01), and the expressions of HIF-1α mRNA and protein increased significantly (0.790 ± 0.161 vs 0.422 ± 0.096, P < 0.01) (0.893 ± 0.080 vs 0.346 ± 0.008, P < 0.01). The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonary hypertension.

Effect of administration of lead nitrate to pregnant rats on the lungs in their offspring.

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Lebed'ko, O A; Ryzhavskii, B Ya

2005-06-01

Lead nitrate in a dose of 200 mg/kg was administered to female rats via a gartric tube on days 5 and 12 of pregnancy. The lungs of their offspring were examined on day 40 of life. We found a decrease in the ratio between the specific volumes of alveolar lumens and interalveolar septa and hypertrophy of lymphoid tissue in the bronchial wall (compared to the offspring of intact females). Chemiluminescent analysis revealed activation of lipid peroxidation and decrease in antioxidant antiradical activity of the lungs.

Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats.

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Chen, Shuchen; Chen, Liangwan; Wu, Xiaonan; Lin, Jiangbo; Fang, Jun; Chen, Xiangqi; Wei, Shijin; Xu, Jianxin; Gao, Qin; Kang, Mingqiang

2012-11-01

It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.

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Qanadli, S D; Orvoen-Frija, E; Lacombe, P; Di Paola, R; Bittoun, J; Frija, G

1999-01-01

The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications.

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Gupta, Sweta K; Dinda, Amit K; Potdar, Pravin D; Mishra, Narayan C

2013-10-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H&E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

International Nuclear Information System (INIS)

Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

1985-01-01

To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

Protein signature of lung cancer tissues.

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Michael R Mehan

Full Text Available Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan to compare protein expression signatures of non small-cell lung cancer (NSCLC tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment.

Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

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Velat Şen

2014-01-01

Full Text Available The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI was found to be associated with increased malondialdehyde (MDA, total oxidant activity (TOA, oxidative stress index (OSI, and decreased total antioxidant capacity (TAC. Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P<0.05. The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

Lung-derived growth factors: possible paracrine effectors of fetal lung development

International Nuclear Information System (INIS)

Montes, A.M.

1985-01-01

A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

Binding sites for endothelin-1 in rat tissues: An autoradiographic study

International Nuclear Information System (INIS)

Koseki, C.; Imai, M.; Hirata, Y.; Yanagisawa, M.; Masaki, T.

1989-01-01

By tissue autoradiography in the rat, we demonstrated that receptors for endothelin-1 (ET-1) were distributed not only in the cardiovascular system but also in the noncardiovascular organs including the brain, lung, intestine, etc. In the brain, the receptors were mainly found in the basal ganglia and brainstem, in which nuclei are known to be cardiovascular regulatory sites. In addition to its direct vasoconstricting action, ET-1 may exert neural cardiovascular control as a neuropeptide

Analysis of lung tissue particles among silicosis cases

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B Case

2005-10-01

Full Text Available Background and Aims:Lung tissue samples of several miners, millers, sandblaster, welders andconstruction workers with historical exposure to mineral particles were analyzed. These subjectshad significant respiratory exposure to silica particles and demanded compensation foroccupational lung diseases.Method: Lung tissue samples were observed under an Electron microscope with 10000Xmagnification. Mineral particles were sized and analyzed by EDS detector based on X-rayspectrophotometry.Results: The results have indicated that the lung particle burden of the subjects was closelyrelated to their occupational history. The highest level of mineral silica particles were found in thelungs of miners and sandblasters. The highest concentration of metallic particles was found in thelungs of welders and miners in ferric mining industry. Severity of lung fibrosis was directlyrelated to the lung free silica concentration. However, no association was found between particlediameter and severity of fibrosis. In addition, lung particle burden of silicotic cases with lungcancer contained a much higher concentration of metallic particles and asbestos fibres that thelung of those subject with silicosis only.Conclusion: Although workers in mining and construction may be predominantly exposed tosilica particles including quartz, the role of other mineral particles including asbestos fibres,metallic fibres and other minerals should be taken into account in the genesis of occupational lungdisease in particular lung cancer. Lung tissue sample analysis can provide valuable informationto assess the legal and compensation cases.

Molecular characterization of radon-induced rat lung tumors

International Nuclear Information System (INIS)

Guillet Bastide, K.

2008-11-01

The radon gas is a well known lung carcinogenic factor in human at high doses but the cancer risk at low doses is not established. Indeed, epidemiological studies at low doses are difficult to conduct because of the human exposure to other lung carcinogenic factors. These data underlined the necessity to conduct experiments on lung tumors developed on animal model. The aim of this work was to characterize rat lung tumors by working on a series of radon-induced tumors that included adenocarcinomas (A.C.), squamous cell carcinomas (S.C.C.) and adeno-squamous carcinomas (A.S.C.), that are mixed tumors with both A.C. and S.C.C. cellular components. A C.G.H. analysis of the three types of tumors allowed us to define chromosomal recurrent unbalances and to target candidate genes potentially implicated in lung carcinogenesis, as p16Ink4a, p19Arf, Rb1, K-Ras or c-Myc. A more precise analysis of the p16Ink4a/Cdk4/Rb1 and p19Arf/Mdm2/Tp53 pathways was performed and indicated that the Rb1 pathway was frequently inactivated through an absence of p16 Ink4a protein expression, indicating that it has a major role in rat lung carcinogenesis. Finally, a comparative transcriptomic analysis of the three types of tumors allowed us to show for the first time that the complex tumors A.S.C. have a transcriptomic profile in accordance with their mixed nature but that they also display their own expression profiles specificities. This work allowed us to find molecular characteristics common to murine and human lung tumors, indicating that the model of lung tumors in rat is pertinent to search for radiation-induced lung tumors specificities and to help for a better molecular identification of this type of tumors in human. (author)

Protective Effects of Alpha-Lipoic Acid on Oleic Acid-Induced Acute Lung Injury in Rats

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Funda Gülcü Bulmuş

2013-09-01

Full Text Available Background: Oxidative stress is believed to be an important factor in the pathogenesis of acute lung injury (ALI. Aims: The aim of this study was to investigate the possible protective role of alpha-lipoic acid (α-LA on oleic acid (OA-induced ALI in rats. Study Design: Animal experiment. Methods: A total of thirty-five rats were divided into five groups in the study. Group 1 served as a control group. Rats in Group 2 (α-LA were administered α-LA intraperitoneally at a dose of 100 mg/kg body weight (BW. Rats in Group 3 (OA were administered OA intravenously at a dose of 100 mg/kg BW. In Group 4 (pre-OA-α-LA, α-LA was given 15 minutes prior to OA infusion, and in Group 5 (post-OA-α-LA, α-LA was given two hours after OA infusion. Four hours after the OA infusion, rats were decapitated. Blood samples were collected to measure serum levels of malondialdehyde (MDA and glutathione (GSH, and the levels of activity for superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GSH-Px. Lung tissue samples were taken for histopathological examination. Results: Exposure to OA resulted in increases in serum MDA levels (p<0.001, as well as histopathological lesions in lung tissue, and decreases in CAT (p<0.05, GSH-Px (p<0.05 activities and GSH (p<0.05 levels. On the other hand, MDA levels were decreased significantly (p<0.001, while CAT (p<0.05, GSH-Px (p<0.01 activities and GSH (p<0.05 levels were increased significantly in the pre-OA-α-LA group compared with the OA group. Conclusion: α-LA was found to lessen oxidative stress and to have positive effects on antioxidants in cases of OA-induced ALI. In conclusion, α-LA appears to have protective effects against ALI and potential for the prevention of ALI.

Use of archived tissues for studies of plutonium-induced lung tumors

International Nuclear Information System (INIS)

Sanders, C.L.; McDonald, K.E.; Lauhala, K.E.; Frazier, M.E.

1988-10-01

Previous lifespan studies in rats exposed to plutonium-239 aerosols indicated that lung tumor incidence might be increased at radiation doses to the lung comparable to doses received by humans from a maximum permissible occupational lung deposition of 0.6 kBq 239 Pu. A total of 3,192 young adults, female, SPF, Wistar rats were used in the initial lifespan study: 2,134 were exposed to 239 PuO 2 at initial lung burdens (ILB) ranging from 0.009 to 6.7 kBq, and 1,058 were sham-exposed controls. Histopathological analyses have been completed on 1707 of the 3,192 rats, including 54 sham-exposed control sand 1153 exposed animals. Cell kinetics, autoradiographic and morphometric techniques are being used to evaluate the spatial-temporal dose-distribution patterns and the cellular events leadings up to lung tumor formation in 140 serially sacrificed female, Wistar rats given a single exposure to 239 PuO 2 (ILB, 3.9 kBq). Protooncogene activation, growth factors and growth factor receptors, DNA cell content (by cell flow cytometry and microspectrophotometry) and cell proliferation (by 3 H-TdR nuclear labeling) are being examined in archival paraffin-block sections. 27 refs., 2 figs

Relation between radiation-induced whole lung functional loss and regional structural changes in partial irradiated rat lung

International Nuclear Information System (INIS)

Luijk, Peter van; Novakova-Jiresova, Alena; Faber, Hette; Steneker, Marloes N.J.; Kampinga, Harm H.; Meertens, Haarm; Coppes, Robert P.

2006-01-01

Purpose: Radiation-induced pulmonary toxicity is characterized by dose, region, and time-dependent severe changes in lung morphology and function. This study sought to determine the relation between the structural and functional changes in the irradiated rat lung at three different phases after irradiation. Materials and Methods: Six groups of animals were irradiated to 16-22 Gy to six different lung regions, each containing 50% of the total lung volume. Before and every 2 weeks after irradiation, the breathing rate (BR) was measured, and at Weeks 8, 26, and 38 CT was performed. From the computed tomography scans, the irradiated lung tissue was delineated using a computerized algorithm. A single quantitative measure for structural change was derived from changes of the mean and standard deviation of the density within the delineated lung. Subsequently, this was correlated with the BR in the corresponding phase. Results: In the mediastinal and apex region, the BR and computed tomography density changes did not correlate in any phase. After lateral irradiation, the density changes always correlated with the BR; however, in all other regions, the density changes only correlated significantly (r 2 = 0.46-0.85, p < 0.05) with the BR in Week 26. Conclusion: Changes in pulmonary function correlated with the structural changes in the absence of confounding heart irradiation

Ischemia and reperfusion of the lung tissues induced increase of lung permeability and lung edema is attenuated by dimethylthiourea (PP69).

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Chen, K H; Chao, D; Liu, C F; Chen, C F; Wang, D

2010-04-01

This study sought to determine whether oxygen radical scavengers of dimethylthiourea (DMTU), superoxide dismutase (SOD), or catalase (CAT) pretreatment attenuated ischemia-reperfusion (I/R)-induced lung injury. After isolation from a Sprague-Dawley rat, the lungs were perfused through the pulmonary artery cannula with rat whole blood diluted 1:1 with a physiological salt solution. An acute lung injury was induced by 10 minutes of hypoxia with 5% CO2-95% N2 followed by 65 minutes of ischemia and then 65 minutes of reperfusion. I/R significantly increased microvascular permeability as measured by the capillary filtration coefficient (Kfc), lung weight-to-body weight ratio (LW/BW), and protein concentration in bronchoalveolar lavage fluid (PCBAL). DMTU pretreatment significantly attenuated the acute lung injury. The capillary filtration coefficient (P<.01), LW/BW (P<.01) and PCBAL (P<.05) were significantly lower among the DMTU-treated rats than hosts pretreated with SOD or CAT. The possible mechanisms of the protective effect of DMTU in I/R-induced lung injury may relate to the permeability of the agent allowing it to scavenge intracellular hydroxyl radicals. However, whether superoxide dismutase or catalase antioxidants showed protective effects possibly due to their impermeability of the cell membrane not allowing scavenging of intracellular oxygen radicals. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

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Melissa L. Bates

2017-04-01

Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVA allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

Trace element load in cancer and normal lung tissue

International Nuclear Information System (INIS)

Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

1999-01-01

Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

International Nuclear Information System (INIS)

Yu, Lunyin; Hales, Charles A

2011-01-01

Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

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

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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.

Fractional energy absorption from beta-emitting particles in the rat lung

International Nuclear Information System (INIS)

Snipes, M.B.

1977-01-01

Forty-four male, Fischer-344 rats were exposed nose-only to an aerosol of 144 Ce in fused aluminosilicate particles to obtain a relatively insoluble lung burden of this material. Twenty-eight rats, ages 12 to 25 weeks with body weights of 183 to 337 grams were analyzed seven to nine days after exposure; lung burdens were 13 to 82 nCi. An additional group of 16 rats was exposed when 12 weeks old and maintained for six months prior to analysis; body weights and lung burdens at six months after exposure ranged from 276 to 368 grams and 16 to 46 nCi, respectively. Lungs were analyzed, inflated and deflated in a 4π beta spectrometer to determine fractional energy absorption for 144 Ce. Over the relatively narrow range of sizes, 0.88 to 1.66 grams, for lungs in this study the average fractional energy absorption and its standard deviation was 0.23 +- 0.078 for the inflated lung and 0.40 +- 0.087 for the deflated lung

Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide.

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Ghorbel, Imen; Chaâbane, Mariem; Boudawara, Ons; Kamoun, Naziha Grati; Boudawara, Tahia; Zeghal, Najiba

2016-10-01

Aluminum chloride (AlCl3) and acrylamide (ACR) are well known as environmental pollutants inducing oxidative stress. Our study investigated the effects of these contaminants and if the hydrophilic fraction of extra virgin olive oil was able to prevent lung oxidative stress and DNA damage. Animals were divided into four groups of six each: group 1, serving as controls, received distilled water; group 2 received in drinking water aluminum chloride (50 mg/ kg body weight) and by gavage acrylamide (20 mg/kg body weight); group 3 received both aluminum and acrylamide in the same way and the same dose as group 2 and hydrophilic fraction from olive oil (OOHF) (1 ml) by gavage; group 4 received only OOHF by gavage. Exposure of rats to both aluminum and acrylamide provoked oxidative stress in lung tissue based on biochemical parameters and histopathological alterations. In fact, we have observed an increase in malondialdehyde (MDA), H2O2, and advanced oxidation protein product (AOPP) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH), and vitamin C levels. Activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were also decreased. Histopathological changes in lung tissue were noted like emphysema, vascular congestion, and infiltration of inflammatory cells. A random DNA degradation was observed on agarose gel in the lung of AlCl3 and acrylamide (ACR)-treated rats. Co-administration of OOHF to treated rats improved biochemical parameters to near control values and lung histoarchitecture. The smear formation of genomic DNA was reduced. The hydrophilic fraction of extra virgin olive oil might provide a basis for developing a new dietary supplementation strategy in order to prevent lung tissue damage.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

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Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Calculations of dose distributions in the lungs of a rat model irradiated in the thermal column of the TRIGA reactor in Pavia

Energy Technology Data Exchange (ETDEWEB)

Protti, N. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy)], E-mail: nicoletta.protti@pv.infn.it; Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); De Bari, A.; Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); Ferrari, C.; Clerici, A.M.; Zonta, C. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); Dionigi, P.; Zonta, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy)

2009-07-15

To test the possibility to apply boron neutron capture therapy (BNCT) to lung tumors, some rats are planned to be irradiated in the thermal column of the TRIGA reactor of University of Pavia. Before the irradiation, lung metastases will be induced in BDIX rats, which will be subsequently infused with boronophenylalanine (BPA). During the irradiation, the rats will be positioned in a box designed to shield the whole animal except the thorax area. In order to optimize the irradiation set-up and to design a suitable shielding box, a set of calculations were performed with the MCNP Monte Carlo transport code. A rat model was constructed using the MCNP geometry capabilities and was positioned in a box with walls filled with lithium carbonate. A window was opened in front of the lung region. Different shapes of the holder and of the window were tested and analyzed in terms of the dose distribution obtained in the lungs and of the dose absorbed by the radiosensitive organs in the rat. The best configuration of the holder ensures an almost uniform thermal neutron flux inside the lungs ({phi}{sub max}/{phi}{sub min}=1.5), an irradiation time about 10 min long, to deliver at least 40 Gy{sub w} to the tumor, a mean lung dose of 5.9{+-}0.4 Gy{sub w}, and doses absorbed by all the other healthy tissues below the tolerance limits.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

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Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

Histopathology of lung disease in the connective tissue diseases.

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Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of ghrelin on inflammatory response in lung contusion

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Berrak Guven

2013-02-01

Full Text Available The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300–400 g were randomly assigned into three groups: control group (n = 6, lung contusion plus saline (saline-treated, n = 12, and lung contusion plus ghrelin (ghrelin-treated, n = 12. Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA. Tissue transforming growth factor-beta 1 (TGF-β1 and matrix metalloproteinase-2 (MMP-2 levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

International Nuclear Information System (INIS)

Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

1990-01-01

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

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Das K

2003-01-01

Full Text Available BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001 higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001 attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

Pathomorphologic observation on treatment of radiation-induced lung damage in rats with

International Nuclear Information System (INIS)

Ye Jiangfeng; Qi Haowen; Zhao Feng; Fan Fengyun; Shi Mei; Zhao Yiling; Meng Yulin

2004-01-01

Objective: To inquire into the means of preventing lung damage induced by thoracic irradiation. Methods: SD rats were divided randomly into 3 groups: normal control, irradiated control (Group IC) and irradiated and fluvastatin (Flu)-treated group (Group F). The later two groups of rats were irradiated with X-rays at a dose of 20 Gy thoracically. Beginning from the seventh day before irradiation the rats in the Group F were treated with Flu at a dose of 20 mg per day by garaging until the end of the experiment. Animals from each group were sacrificed on days 5, 15, 30, 60 respectively after irradiation. Sections of lung were examined with light microscopy, electron microscopy and morphometry. Results: The rats in the Group IC suffered from typical radiation pneumonitis (P<0.01). Electron microscopy indicated type II pneumonocytes and capillary endothelial cells were injured in rats of Group IC on days 30, 60. There were increase of collagen and a great quantity of mast cells in irradiated control rats. In rats of the Group F there was slight reaction in the lung. Conclusion: Fluvastatin could reduce radiation pneumonitis and inhibit increase of collagen. The treatment and prevention of radiation-induced lung injury in rats with fluvastatin is effective

Kinetics of reversible-sequestration of leukocytes by the isolated perfused rat lung

Energy Technology Data Exchange (ETDEWEB)

Goliaei, B.

1980-08-01

The kinetics and morphology of sequestration and margination of rat leukocytes were studied using an isolated perfused and ventilated rat lung preparation. Whole rat blood, bone marrow suspension, or leukocyte suspensions, were used to perfuse the isolated rat lung. The lung was also perfused with latex particle suspensions and the passage of particles through the lung capillaries was studied. When a leukocyte suspension was perfused through the lung in the single-pass mode, the rate of sequestration decreased as more cells were perfused. In contrast, latex particles of a size comparable to that of leukocytes were totally stopped by the lung. When the leukocyte suspension was recirculated through the lung, cells were rapidly removed from circulation until a steady state was reached, after which no net removal of cells by the lung occurred. These results indicate that leukocytes are reversibly sequestered from circulation. The sequestered cells marginated and attached to the luminal surface of the endothelium of post-capillary venules and veins. A mathematical model was developed based on the assumption that the attachment and detachment of leukocytes to blood vessel walls follows first-order kinetics. The model correctly predicts the following characteristics of the system: (a) the kinetics of the sequestration of leukocytes by the lung; (b) the existence of a steady state when a suspension of leukocytes is recirculated through the lung; and (c) the independence of the fraction of cells remaining in circulation from the starting concentration for all values of starting concentration. (ERB)

Involvement of growth factors and their receptors in radon-induced rat lung tumors

International Nuclear Information System (INIS)

Leung, F.C.; Dagle, G.E.; Cross, F.T.

1992-01-01

In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-α), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-α, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway

Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

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Uhlig, S; Nüsing, R; von Bethmann, A; Featherstone, R L; Klein, T; Brasch, F; Müller, K M; Ullrich, V; Wendel, A

1996-05-01

Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1.

Ischemia-reperfusion injury in the isolated rat lung. Role of flow and endogenous leukocytes.

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Seibert, A F; Haynes, J; Taylor, A

1993-02-01

Microvascular lung injury caused by ischemia-reperfusion (IR) may occur via leukocyte-dependent and leukocyte-independent pathways. Leukocyte-endothelial adhesion may be a rate-limiting step in IR lung injury. Leukocyte adhesion to microvascular endothelium occurs when the attractant forces between leukocyte and endothelium are greater than the kinetic energy of the leukocyte and the vascular wall shear rate. We hypothesized (1) that isolated, buffer-perfused rat lungs are not free of endogenous leukocytes, (2) that endogenous leukocytes contribute to IR-induced microvascular injury as measured by the capillary filtration coefficient (Kfc), and (3) that a reduction of perfusate flow rate would potentiate leukocyte-dependent IR injury. Sixty lungs were divided into four groups: (1) low-flow controls, (2) high-flow controls, (3) low-flow IR, and (4) high-flow IR. Microvascular injury was linearly related to baseline perfusate leukocyte concentrations at both low (r = 0.78) and high (r = 0.82) flow rates. Kfc in the high-flow IR group (0.58 +/- 0.03 ml/min/cm H2O/100 g) was less (p Kfc in the low-flow IR group (0.82 +/- 0.07), and in both groups Kfc values were significantly greater than low-flow (0.34 +/- 0.03) and high-flow (0.31 +/- 0.01) control Kfc values after 75 min. Retention of leukocytes in the lung, evaluated by a tissue myeloperoxidase assay, was greatest in the low-flow IR group. We conclude (1) that isolated, buffer-perfused rat lungs contain significant quantities of leukocytes and that these leukocytes contribute to IR lung injury, and (2) that IR-induced microvascular injury is potentiated by low flow.

Adverse effect of nano-silicon dioxide on lung function of rats with or without ovalbumin immunization.

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Bing Han

Full Text Available BACKGROUND: The great advances of nanomaterials have brought out broad important applications, but their possible nanotoxicity and risks have not been fully understood. It is confirmed that exposure of environmental particulate matter (PM, especially ultrafine PM, are responsible for many lung function impairment and exacerbation of pre-existing lung diseases. However, the adverse effect of nanoparticles on allergic asthma is seldom investigated and the mechanism remains undefined. For the first time, this work investigates the relationship between allergic asthma and nanosized silicon dioxide (nano-SiO₂. METHODOLOGY/PRINCIPAL FINDINGS: Ovalbumin (OVA-treated and saline-treated control rats were daily intratracheally administered 0.1 ml of 0, 40 and 80 µg/ml nano-SiO₂ solutions, respectively for 30 days. Increased nano-SiO₂ exposure results in adverse changes on inspiratory and expiratory resistance (Ri and Re, but shows insignificant effect on rat lung dynamic compliance (Cldyn. Lung histological observation reveals obvious airway remodeling in 80 µg/ml nano-SiO₂-introduced saline and OVA groups, but the latter is worse. Additionally, increased nano-SiO₂ exposure also leads to more severe inflammation. With increasing nano-SiO₂ exposure, IL-4 in lung homogenate increases and IFN-γ shows a reverse but insignificant change. Moreover, at a same nano-SiO₂ exposure concentration, OVA-treated rats exhibit higher (significant IL-4 and lower (not significant IFN-γ compared with the saline-treated rats. The percentages of eosinophil display an unexpected result, in which higher exposure results lower eosinophil percentages. CONCLUSIONS/SIGNIFICANCE: This was a preliminary study which for the first time involved the effect of nano-SiO₂ to OVA induced rat asthma model. The results suggested that intratracheal administration of nano-SiO₂ could lead to the airway hyperresponsiveness (AHR and the airway remolding with or without OVA

Connective tissue diseases, multimorbidity and the ageing lung.

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Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs.

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Lin, Chia-Chih; Hsieh, Nan-Kuang; Liou, Huey Ling; Chen, Hsing I

2012-03-01

Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial

Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs

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Lin Chia-Chih

2012-03-01

Full Text Available Abstract Background Phorbol myristate acetate (PMA is a strong neutrophil activator and has been used to induce acute lung injury (ALI. Niacinamide (NAC is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC on the PMA-induced ALI and associated changes. Methods The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g, PMA 4 μg/g (lung weight, cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight. There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc were determined in isolated lungs. ATP (adenotriphosphate and PARP [poly(adenosine diphophate-ribose polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS. The neutrophil-derived mediators in lung perfusate were determined. Results PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Conclusions Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental

Angiotensin-(1–7 inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

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W. Lu

2016-01-01

Full Text Available Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7] on lung injury in rats induced by chronic intermittent hypoxia (CIH. We randomly assigned 32 male Sprague-Dawley rats (180–200 g to normoxia control (NC, CIH-untreated (uCIH, Ang-(1–7-treated normoxia control (N-A, and Ang-(1–7-treated CIH (CIH-A groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4 and Nox subunits (p22phox, and p47phox was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01. Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1–7 treatment. In summary, treatment with Ang-(1-7 reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.

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.

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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

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

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Lee JA

2014-12-01

Full Text Available Jeong-A Lee,1 Mi-Kyung Kim,1 Hee-Jeong Paek,1 Yu-Ri Kim,2 Meyoung-Kon Kim,2 Jong-Kwon Lee,3 Jayoung Jeong,3 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Republic of Korea; 3Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk–do, Republic of Korea Purpose: The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods: Silica nanoparticles of two different sizes (20 nm and 100 nm were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results: The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion: The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ

Production of decellularized porcine lung scaffolds for use in tissue engineering.

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Balestrini, Jenna L; Gard, Ashley L; Liu, Angela; Leiby, Katherine L; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpell, Stuart G; Niklason, Laura E

2015-12-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual DNA, biochemical composition, mechanical characteristics, tissue architecture, and recellularization capacity.

Effect of flavones on rat brain and lung matrix metalloproteinase activity measured by film in-situ zymography.

Science.gov (United States)

Sasaki, K; Tateoka, N; Ando, H; Yoshizaki, F

2005-04-01

We have evaluated the inhibitory activity of flavone, nobiletin, and heptamethoxyflavone on matrix metalloproteinase (MMP) activity in the rat. MMP in 9000-g supernatant fraction of lung homogenate was activated by p-aminophenyl mercuric acetate (APMA), and gelatinolytic activity was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Coomassie staining. This activity should be related to MMP-2 and/or MMP-9 and was confirmed by gelatin zymography. Fluorescent-conjugated collagen used as a substrate for collagenolytic activity wasinvestigated by SDS-PAGE also. The film in-situ zymography method was applied to rat brain and lung tissue in the same manner. Flavone and nobiletin inhibited the APMA-stimulated gelatinolytic activity and also the collagenolytic activity by more than 75%. The film in-situ zymography method indicated that these compounds might be potent inhibitors of MMP, suggesting the specific inhibition of localized MMP in brain hippocampus and/or lung terminal bronchioles, which may contribute to the prevention of some types of brain disease or cancer invasion and metastasis.

Cyclin D expression in plutonium-induced lung tumors in F344 rats

Energy Technology Data Exchange (ETDEWEB)

Hahn, F.F.; Kelly, G. [SouthWest Scientific Resources, Inc., Albuquerque, NM (United States)

1995-12-01

The genetic mechanisms responsible for {alpha}-radiation-induced lung cancer in rats following inhalation of {sup 239}Pu is an ongoing area of research in our laboratory. Previous studies have examined the status of the p53 gene by immunohistochemistry. Only two tumors (2/26 squamous cell carcinomas) exhibited detectable levels of p53 products. Both were the result of mutations in codons 280 and 283. More recent studies of X-ray-induced lung tumors in rats showed a similar lack of involvement of p53. In conclusion, we found that {alpha}-radiation-induced rat lung tumors have a high incidence (31 of 39) of cyclin D{sub 1} overexpression.

Measurement of asbestos bodies in lung tissue of autopsy cases diagnosed with primary lung cancer

International Nuclear Information System (INIS)

Idei, Yuka; Kamada, Satoe; Matsumoto, Shoji; Ohnishi, Kazuo; Kitazawa, Riko; Kitazawa, Sohei

2007-01-01

To investigate the relation between asbestos-related lung cancer and the concentration of asbestos bodies in lung tissue, we analyzed the concentration in 24 autopsy cases diagnosed with primary lung cancer, with regard to the gender, age, histological type of lung cancer and occupation of each case. The asbestos bodies were measured according to Kohyama's method. Positive cases (more than 5,000 bodies per 1 g of dry lung tissue) were further analyzed for asbestosis and pleural plaques by chest X-ray and chest CT. Two cases exhibited more than 5,000 bodies, five cases between 1,000 and 5,000, and seventeen cases less than 1,000. The occupation of the two positive cases was not informative: one demonstrated neither asbestosis nor pleural plaques, and the other showed only pleural plaques. Although the number of cases of asbestos-related lung cancer is minimal among all lung cancer cases, the number of the former may exceed that of mesothelioma patients. Not only physicians but also radiologists, surgeons and pathologists need to collaborate in the diagnosis of asbestos-related lung cancer. (author)

Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

Directory of Open Access Journals (Sweden)

Kummer Wolfgang

2006-07-01

Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

32P-postlabeling DNA adduct assay: cigarette smoke-induced dna adducts in the respiratory and nonrespiratory rat tissues. Book chapter

International Nuclear Information System (INIS)

Gupta, R.C.; Gairola, C.G.

1990-01-01

An analysis of the tissue DNA adducts in rats by the sensitive (32)p-postlabeling assay showed one to eight detectable DNA adducts in lung, trachea, larynx, heart and bladder of the sham controls. Chronic exposure of animals to mainstream cigarette smoke showed a remarkable enhancement of most adducts in the lung and heart DNA. Since cigarette smoke contains several thousand chemicals and a few dozen of them are known or potential carcinogens, the difference between the DNA adducts of nasal and the other tissues may reflect the diversity of reactive constituents and their differential absorption in different tissues. In comparison to the lung DNA adducts, the adducts in nasal DNA were less hydrophobic. Identity of the predominant adducts was further investigated by comparison with several reference DNA adducts from 10 PAH and aromatic amines. Since some of these chemicals are present in cigarette smoke, the results suggest that these constituents of cigarette smoke may not be directly responsible for formation of DNA adducts in the lung and heart of the smoke-exposed animals

Influence of long-term drinking alcohol on the cytokines in the rats with endogenous and exogenous lung injury.

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Liu, Y D; Liu, W; Liu, Z

2013-02-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are syndromes of acute respiratory failure. Exploration of the impacts of long-term drinking alcohol on the cytokines of rats with endogenous and exogenous lung injuries. Through giving the model rats long-term drinking alcohol or water, we acquired the changes of the cytokines in the serum and bronchoalveolar lavage fluid (BALF) of these rats with lung injuries due to different incentives. The partial pressure of oxygen in rats with lung damage after long-term drinking alcohol were significantly lower than those drinking water group (p exogenous lung injury were higher than those of rats with endogenous lung injury (p endogenous lung injury were higher than those with exogenous lung injury (p exogenous lung injury. The expression of TNF-α, IL-6 and IL-10 are different according to the different ways that lead to the acute lung injury.

[Protective effect of tanshinol on the hepatopulmonary syndrome in rat].

Science.gov (United States)

Jia, Jian-Tao; Zhang, Hui-Ying; Lai, Li-Na; Li, Xu-Jiong; Tian, Xiao-Xia; Zhang, Li-Li; Lv, Min-Li; Zhao, Zhong-Fu; Han, De-Wu; Cheng, Ji

2014-05-01

To explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS). SD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively. Thickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group. Tanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.

Protective effects of lipoic acid against oxidative stress induced by lead acetate and gamma-irradiation in the kidney and lung in albino rats

International Nuclear Information System (INIS)

Rezk, R.G.; Abdel-Rahman, N.A.

2013-01-01

Lipoic acid is widely used as antioxidant that protects tissues against a range of oxidative stress. The present study was designed to determine the protective effect of lipoic acid against oxidative organ damage induced by lead intoxication and/or gamma-irradiation. Rats were treated daily intrapritonealy (i. p.) with lipoic acid( 200 mg/kg/b.w.) for 15 consecutive days before lead acetate injection(30 mg/kg/b.w) i.p. for 5 days and/ or whole body. gamma-irradiation (3 Gy). Animals were sacrificed on the 3rd day post the last treatment. Histological examination of kidney and lung tissues through light microscope showed that lead acetate injection and/or exposure to gamma radiation has provoked severe architectural damage in both tissues as necrotic lesions, atrophoid glomerulei and degenerated proximal and distal convoluted tubules, severe bronchiole fibrosis, decreased ciliated bronchioles and dilated and widened pulmonary artery. Histological damage was associated with significant biochemical. changes as increase in lead, copper, iron, zinc and calcium levels in both kidney and lung tissues. Kidney and lung of rats treated with lipoic acid before lead intoxication and/or gamma-irradiation showed significant regenerated glomerulei structure, well-defined structure of proximal and distal convoluted tubules, regenerated ciliated bronchiole structure and improved pulmonary artery. Tissue regeneration was associated with significant decrease in Pb, Cu, Fe, Zn, and Ca levels in kidney and lung and prevented the accumulation of metals in these organs. It could be concluded that lipoic acid administration before lead and/or whole body gamma-irradiation might be capable to attenuate lead and/or gamma radiation induced organ injury and organ metals disruption

Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway.

Science.gov (United States)

Qing, Rui; Huang, Zezhi; Tang, Yufei; Xiang, Qingke; Yang, Fan

2018-04-24

The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism. Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay. Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues. The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression. Copyright © 2018. Published by Elsevier B.V.

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

Energy Technology Data Exchange (ETDEWEB)

Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden)

2016-10-15

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment

Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue.

Science.gov (United States)

Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, Ugur; Simsek, Tuncer

2017-12-30

The aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy  group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.

Production of decellularized porcine lung scaffolds for use in tissue engineering†

Science.gov (United States)

Balestrini, Jenna L.; Gard, Ashley L.; Liu, Angela; Leiby, Katherine L.; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A.; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpella, Stuart G.; Niklason, Laura E.

2015-01-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual PMID:26426090

[The morphofunctional changes in the rat lung tissue during simulation of acute fatal poisoning with household gas].

Science.gov (United States)

Kalinina, E Iu; Iagmurov, O D

2014-01-01

The methods of light microscopy, immunohistochemistry, and electron microscopy were employed to study the morphofunctional changes in epithelium of bronchial and respiratory segments of the rat lungs used as models of acute fatal poisoning with household gas. It was shown that this toxic effect induces the pathological process involving all the elements of the epithelial layer in the bronchial and respiratory segments of the lungs of experimental animals. At the ultrastructural level, mitochondria and endoplasmic reticulum structures are affected, with the death of epithelial cells leading to the damage of the aerohematic barrier. The toxic effect of the gaseous mixture on the membranes causes the destruction of various elements of the epithelial layer. The results of this study help to understand the mechanisms of death in the case of acute fatal poisoning with household gas.

Seawater immersion aggravates burn-associated lung injury and inflammatory and oxidative-stress responses.

Science.gov (United States)

Ma, Jun; Wang, Ying; Wu, Qi; Chen, Xiaowei; Wang, Jiahan; Yang, Lei

2017-08-01

With the increasing frequency of marine development activities and local wars at sea, the incidence of scald burns in marine accidents or wars has been increasing yearly. Various studies have indicated that immersion in seawater has a systemic impact on some organs of animals or humans with burn. Thus, for burn/scald injuries after immersion in seawater, it is desirable to study the effects and mechanisms of action on important organs. In the present study, we aimed to investigate the effect of immersion in seawater on lung injury, inflammatory and oxidative-stress responses in scalded rats. The structural damage to lungs was detected by hematoxylin and eosin staining and the results showed that seawater immersion aggravated structural lung injury in scalded rats. The expression of HMGB1 in lung tissues was detected by immunohistochemical analysis and the results showed that seawater immersion increased HMGB1 expression in lung tissues of scalded rats. Apoptosis in lung tissues was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and the results showed that seawater immersion increased apoptosis rate in lung tissues of scalded rats. In addition, the expression levels of TNF-α, IL-6, IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays (ELISAs) and the results showed that seawater immersion induced secretion of proinflammatory factors (TNF-α, IL-6, and IL-8), increased MDA protein level, and suppressed SOD activity in the serum of scalded rats. Furthermore, measurement of plasma volume and pH showed that seawater immersion decreased plasma volume and pH value. Overall, the results indicated that all effects induced by immersion in seawater in scalded rats are more pronounced than those induced by freshwater. In conclusion, seawater immersion may aggravate lung injury and enhance inflammatory and oxidative-stress responses after burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights

Integrating microRNA and mRNA expression profiles in response to radiation-induced injury in rat lung

International Nuclear Information System (INIS)

Xie, Ling; Zhou, Jundong; Zhang, Shuyu; Chen, Qing; Lai, Rensheng; Ding, Weiqun; Song, ChuanJun; Meng, XingJun; Wu, Jinchang

2014-01-01

Exposure to radiation provokes cellular responses, which are likely regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which regulate gene expression by promoting mRNA degradation or inhibiting protein translation. The expression patterns of both mRNA and miRNA during the radiation-induced lung injury (RILI) remain less characterized and the role of miRNAs in the regulation of this process has not been studied. The present study sought to evaluate miRNA and mRNA expression profiles in the rat lung after irradiation. Male Wistar rats were subjected to single dose irradiation with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and morphological changes in the lung were examined by haematoxylin and eosin. The miRNA and mRNA expression profiles were evaluated by microarrays and followed by quantitative RT-PCR analysis. A cDNA microarray analysis found 2183 transcripts being up-regulated and 2917 transcripts down-regulated (P ≤ 0.05, ≥2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs microarray analysis indicated 15 miRNA species being up-regulated and 8 down-regulated (P ≤ 0.05). Subsequent bioinformatics anal -yses of the differentially expressed mRNA and miRNAs revealed that alterations in mRNA expression following irradiation were negatively correlated with miRNAs expression. Our results provide evidence indicating that irradiation induces alterations of mRNA and miRNA expression in rat lung and that there is a negative correlation of mRNA and miRNA expression levels after irradiation. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of radiation-induced lung injury. In summary, RILI does not develop gradually in a linear process. In fact, different cell types interact via cytokines in a very complex network. Furthermore, this study suggests that

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

Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

Science.gov (United States)

Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

2015-11-01

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy.

Science.gov (United States)

Veith, Lothar; Vennemann, Antje; Breitenstein, Daniel; Engelhard, Carsten; Wiemann, Martin; Hagenhoff, Birgit

2017-07-10

The direct detection of nanoparticles in tissues at high spatial resolution is a current goal in nanotoxicology. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is widely used for the direct detection of inorganic and organic substances with high spatial resolution but its capability to detect nanoparticles in tissue sections is still insufficiently explored. To estimate the applicability of this technique for nanotoxicological questions, comparative studies with established techniques on the detection of nanoparticles can offer additional insights. Here, we compare ToF-SIMS imaging data with sub-micrometer spatial resolution to fluorescence microscopy imaging data to explore the usefulness of ToF-SIMS for the detection of nanoparticles in tissues. SiO 2 nanoparticles with a mean diameter of 25 nm, core-labelled with fluorescein isothiocyanate, were intratracheally instilled into rat lungs. Subsequently, imaging of lung cryosections was performed with ToF-SIMS and fluorescence microscopy. Nanoparticles were successfully detected with ToF-SIMS in 3D microanalysis mode based on the lateral distribution of SiO 3 - (m/z 75.96), which was co-localized with the distribution pattern that was obtained from nanoparticle fluorescence. In addition, the lateral distribution of protein (CN - , m/z 26.00) and phosphate based signals (PO 3 - , m/z 78.96) originating from the tissue material could be related to the SiO 3 - lateral distribution. In conclusion, ToF-SIMS is suitable to directly detect and laterally resolve SiO 2 nanomaterials in biological tissue at sufficient intensity levels. At the same time, information about the chemical environment of the nanoparticles in the lung tissue sections is obtained.

[Effect of compound hypertonic saline solution on septic rats].

Science.gov (United States)

Dong, Fang; Xu, Liang; Xu, Gang; Wang, Huabing; Lu, Huizhi; Cai, Liping

2015-01-01

To study the effect of compound hypertonic saline solution ( HSD ) on sepsis. 133 male Wistar rats were divided into four groups, sham operation group ( n = 15 ), cecal ligation and puncture ( CLP ) group ( n = 45 ), CLP plus normal saline ( NS ) group ( n = 45 ), and CLP plus HSD group ( n = 28 ). A rat model of sepsis was reproduced by CLP, and the rats in sham operation group received celiotomy without ligation and puncture. All rats in four groups received subcutaneous injection of 30 mL/kg 0.9% sodium chloride after laparotomy. The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9% sodium chloride or 7.5% sodium chloride/6% dextran post CLP via jugular vein for 3 hours, with the infusion rate of 0.4 mL×kg(-1)×min(-1). The survival rate of each group was observed 9 hours and 18 hours after laparotomy. Mean arterial pressure ( MAP ) at 0, 9, 18 hours were monitored. Blood specimens were collected from all rats 0, 9 and 18 hours after laparotomy, respectively, for measurement of the plasma levels of tumor necrosis factor-α ( TNF-α), interleukin-1β ( IL-1β ), and procalcitonin ( PCT ). The rats were all sacrificed, and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid ( BALF ), myeloperoxidase ( MPO ) activity in lung tissue, wet/dry weight ratio ( W/D ) of lung, and pathological changes in lung tissue. There was no death in the sham operation group. The survival rates at 9 hours and 18 hours were 62.2% and 31.1% in the CLP group, 57.8% and 35.6% in the CLP plus NS group, 85.7% and 64.3% in the CLP plus HSD group, and they were all significantly higher compared with those of the CLP group and the CLP plus NS group ( Pmicroscope, no pathobiological changes were found in sham operation group. The lung tissues in the CLP group and the CLP plus NS group showed congestion, edema, infiltrating inflammatory changes, while the inflammatory changes in the lung tissue in the CLP plus HSD group

Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury

OpenAIRE

Cao, Shuo; Wu, Rong

2012-01-01

Objective Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentration...

Long term lung clearance and cellular retention of cadmium in rats and monkeys

International Nuclear Information System (INIS)

Oberdorster, G.; Cox, C.; Baggs, R.

1987-01-01

The paper describes experiments to determine the long term lung clearance and cellular retention of cadmium in rats and monkeys. The rats and monkeys were exposed to 109 Cd Cl 2 aerosols, and one monkey was exposed to 115 CdO particles. The thoracic activity of the respective Cd isotopes was measured with time after exposure, for both species. Accumulation of 109 Cd in the kidneys of the monkeys exposed to 109 Cd Cl 2 was also examined, and autoradiographs of lung sections of these monkeys were also prepared. The results showed that the cadmium accumulated differently in the lungs of the rats and primates. (U.K.)

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom

International Nuclear Information System (INIS)

Company, F.Z.; Allen, B.J.

1998-01-01

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20x20cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings. (author)

Induction of phosphatidylcholine biosynthesis via CDPcholine pathway in lung and liver of rats following intratracheal administration of DDT and endosulfan

International Nuclear Information System (INIS)

Narayan, S.; Dani, H.M.; Misra, U.K.

1989-01-01

The induction of phosphatidylcholine (PC) biosynthesis via the CDPcholine pathway in lung and liver of rats has been shown following the intratracheal administration of 1,1,1-trichloro-2m2-bis(p-chlorophenyl) ethane (DDT) (5 mg/100 g body weight) and endosulfan (1 mg/100 g body weight) for 3 days. Controls received only the vehicle solution (groundnut oil, 0.1 m1/100 g body weight). The treatment of DDT and endosulfan significantly increased the PC contents and the incorporation of radioactive [methyl-3H]choline into PC of lung and liver microsomes. The incorporation of radioactive [methyl-14C]methionine into microsomal PC of lung and liver was not affected significantly by treatment with either of the insecticides. 1,4,5,6,7-hexachloro-5-norbornene-2,3-dimethano cyclic sulfite (endosulfan) administration significantly increased the activity of choline kinase and phosphocholine cytidylyltransferase (both cytosolic and microsomal) of lung, whereas DDT increased the activity of only latter. In liver, both DDT and endosulfan administration significantly increased the activity of choline kinase and phosphocholine cytidylyltransferase (both cytosolic and microsomal). However, the activity of phosphocholinetransferase was not affected in both lung and liver microsomes of rats treated with these insecticides. The PC precursor pool sizes, choline and phosphorylcholine, of lung and liver tissues were not altered by DDT and endosulfan treatments. The present results suggest that the increased level of PC and incorporation of radioactive [methyl-3H]choline into microsomal PC could be the result of increased activity of choline kinase and phosphocholine cytidylyltransferase of lung and liver of rats following intratracheal administration of DDT and endosulfan

Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

Science.gov (United States)

Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

2017-03-01

According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

DEFF Research Database (Denmark)

Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

1998-01-01

OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

A comparative study of lung toxicity in rats induced by three types of nanomaterials

Science.gov (United States)

Lin, Zhiqing; Ma, Li; X, Zhu-ge; Zhang, Huashan; Lin, Bencheng

2013-12-01

The public is increasingly exposed to various engineered nanomaterials because of their mass production and wide application. Even when the biological effects of nanomaterials have been assessed, the underlying mechanisms of action in vivo are poorly understood. The present study was designed to seek a simple, effective, and oxidative stress-based biomarker system used for screening toxicity of nanomaterials. Nano-ferroso-ferric oxide (nano-Fe3O4), nano-silicon dioxide (nano-SiO2), and single-walled carbon nanotubes (SWCNTs) were dispersed in corn oil and characterized using transmission electron microscopy (TEM). Rats were exposed to the three nanomaterials by intratracheal instillation once every 2 days for 5 weeks. We investigated their lung oxidative and inflammatory damage by bronchoalveolar lavage fluid (BALF) detection and comparative proteomics by lung tissue. Two-dimensional electrophoresis (2-DE) of proteins isolated from the lung tissue, followed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, was performed. In the present study, we chose to detect lactate dehydrogenase, total antioxidant capacity, superoxide dismutase, and malondialdehyde as the biomarker system for screening the oxidative stress of nanomaterials and IL-6 as the inflammatory biomarker in BALF. Proteomics analysis revealed 17 differentially expressed proteins compared with the control group: nine were upregulated and eight were downregulated. Our results indicated that exposure by intratracheal instillation to any of the three typical nanomaterials may cause lung damage through oxidative damage and/or an inflammatory reaction.

Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats

International Nuclear Information System (INIS)

Trivillin, V.A.; Garabalino, M.A.; Colombo, L.L.

2013-01-01

Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats Introduction: Boron Neutron Capture Therapy (BNCT) is based on selective tumor uptake of boron compounds, followed by neutron irradiation. BNCT was proposed for the treatment of unresectable, diffuse lung metastases. The aim of the present study was to perform BNCT studies in an experimental model of lung metastases. Materials and Methods: 3 x 106/0.5 ml colon carcinoma cells (DHD/K12/TRb) were injected iv in syngeneic BDIX rats. Three weeks post-inoculation, rats with diffuse lung metastases were used for in vivo BNCT studies in the RA-3 Nuclear Reactor. Based on previous biodistribution studies and computational dosimetry with Monte Carlo simulation, 2 doses were prescribed, i.e. 4 Gy and 8 Gy minimum absorbed dose to tumor. The animals were assigned to 5 experimental groups (n= 4 to 8) at each dose level: T0 (euthanized pre-treatment), BPA-BNCT, Comb-BNCT (BPA+GB-10), Beam only (background dose) and Sham (same manipulation, no treatment). Boron concentration was measured in a blood sample taken pre-irradiation to verify that the value was in the range established in previous biodistribution studies. The animals were followed clinically for 2 weeks after neutron irradiation and then euthanized to assess the response of tumor and normal lung, macroscopically and histologically. To date we have evaluated the end-point weight of lung (normal lung + metastases) and % lung weight/body weight as an indicator of tumor growth. Results: The statistical analysis (ANOVA) of % lung weight/body weight showed statistically significant differences (p<0.05) between groups T0 (0.79 ± 0.38) and Sham (1.87 ± 0.91). No statistically significant differences were observed between the Beam only groups (at both dose levels) and Sham. Similar and statistically significant tumor control was induced in the groups BPA-BNCT Low dose (LD) (0.56 ± 0.11), BPA-BNCT High dose (HD) (0.80 ± 0.16), Comb

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.

Up-regulation of cytochrome P450 and phase II enzyme systems in rat precision-cut rat lung slices by the intact glucosinolates, glucoraphanin and glucoerucin.

Science.gov (United States)

Abdull Razis, Ahmad Faizal; Bagatta, Manuela; De Nicola, Gina Rosalinda; Iori, Renato; Ioannides, Costas

2011-03-01

It is believed that the chemopreventive activity of cruciferous vegetables in the lung and other tissues is exclusively the result of exposure to degradation products of glucosinolates, such as the isothiocyanates, and that the parent glucosinolates make no contribution. In the present study, evidence is presented for the first time that, in rat lung, the intact glucosinolates, glucoraphanin and glucoerucin, can modulate carcinogen-metabolising enzyme systems. The glucosinolates were isolated from cruciferous vegetables and incubated (1-25 μM) with precision-cut rat lung slices for 24h. Both glucosinolates, at concentrations as low as 1 μM, up-regulated the O-deethylation of ethoxyresorufin and the apoprotein levels of CYP1A1 and CYP1B1; supplementation of the incubation medium with myrosinase, the enzyme that converts glucosinolates to their corresponding isothiocyanates, abolished the rise in ethoxyresorufin O-deethylase activity. In contrast, neither glucosinolate, at the concentrations studied, influenced quinone reductase activity in the lung slices, but addition of myrosinase to the glucosinolate incubations led to a marked rise in activity. Glutathione S-transferase activity, monitored using 1-chloro-2,4-dinitrobenzene as the accepting substrate, was elevated in lung slices exposed to glucoraphanin. GSTα protein levels were increased by glucoraphanin and, to a much lesser extent, glucoerucin. It may be concluded that intact glucosinolates can modulate the activity of pulmonary carcinogen-metabolising enzyme systems, and can thus contribute to the documented chemopreventive activity of cruciferous vegetables in the lung. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

No adverse lung effects of 7- and 28-day inhalation exposure of rats to emissions from petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without particulate filter - the FuelHealth project.

Science.gov (United States)

Magnusson, Pål; Oczkowski, Michał; Øvrevik, Johan; Gajewska, Malgorzata; Wilczak, Jacek; Biedrzycki, Jacek; Dziendzikowska, Katarzyna; Kamola, Dariusz; Królikowski, Tomasz; Kruszewski, Marcin; Lankoff, Anna; Mruk, Remigiusz; Brunborg, Gunnar; Instanes, Christine; Gromadzka-Ostrowska, Joanna; Myhre, Oddvar

2017-04-01

Increased use of biofuels raises concerns about health effects of new emissions. We analyzed relative lung health effects, on Fisher 344 rats, of diesel engine exhausts emissions (DEE) from a Euro 5-classified diesel engine running on petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without diesel particulate filter (DPF). One group of animals was exposed to DEE for 7 days (6 h/day), and another group for 28 days (6 h/day, 5 days/week), both with and without DPF. The animals (n = 7/treatment) were exposed in whole body exposure chambers. Animals breathing clean air were used as controls. Genotoxic effects of the lungs by the Comet assay, histological examination of lung tissue, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury, and mRNA markers of inflammation and oxidative stress were analyzed. Our results showed that a minor number of genes related to inflammation were slightly differently expressed in the exposed animals compared to control. Histological analysis also revealed only minor effects on inflammatory tissue markers in the lungs, and this was supported by flow cytometry and ELISA analysis of cytokines in BALF. No exposure-related indications of genotoxicity were observed. Overall, exposure to DEE with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. Overall, exposure to DEE from a modern Euro 5 light vehicle engine run on B20 fuel with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF.

Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

Science.gov (United States)

Sato, Tomohiro; Tamada, Tsutomu; Watanabe, Shigeru; Nishimura, Hirotake; Kanki, Akihiko; Noda, Yasufumi; Higaki, Atsushi; Yamamoto, Akira; Ito, Katsuyoshi

2015-06-01

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

Captopril reduces collagen and mast cell accumulation in irradiated rat lung

International Nuclear Information System (INIS)

Ward, W.F.; Molteni, A.; Ts'ao, C.H.; Hinz, J.M.

1990-01-01

The angiotensin converting enzyme inhibitor captopril ameliorates radiation-induced pulmonary endothelial dysfunction in rats. The present study determined whether captopril also reduces collagen (hydroxyproline) accumulation in the lungs of rats sacrificed 2 months after a range of single doses (0-30 Gy) of 60Co gamma rays to the right hemithorax. Captopril was administered in the feed at a regimen of 0, 25, or 50 mg/kg/day continuously after irradiation. Mast cell counts also were obtained from lungs of all animals exposed to 30 Gy. In rats receiving no captopril, there was a radiation dose-dependent increase in right lung hydroxyproline (HP) content and in HP concentration per g wet weight. Captopril produced a drug dose-dependent suppression in this radiation-induced HP accumulation. At a dose of 50 mg/kg/d, captopril reduced the slope of the radiation dose response curve for lung HP content by a factor of 1.7, and completely prevented the increase in HP concentration. At an isoeffect level of 550 micrograms HP per right superior lobe, this dose of captopril exhibited a DRF of 1.7 +/- 0.2. In rats exposed to 30 Gy, moreover, the number of mast cells per mm2 of alveolar cross-sectional surface area decreased from 105 +/- 8 to 100 +/- 7 and 59 +/- 5 in the groups given 0, 25 or 50 mg/kg/d of captopril, respectively, (vs none in sham-irradiated rats). These data are the first to demonstrate that the ACE inhibitor captopril might provide a novel intervention in the pathogenesis of radiation fibrosis

4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

Science.gov (United States)

Liu, Zhongyang; Xi, Ronggang; Zhang, Zhiran; Li, Wangping; Liu, Yan; Jin, Faguang; Wang, Xiaobo

2014-01-01

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. PMID:25050781

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

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

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs

Directory of Open Access Journals (Sweden)

Kevin M. Rice

2015-05-01

Full Text Available Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2 nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. Results: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05. Conclusions: Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.

Analysis of lung tissue using ion beams

International Nuclear Information System (INIS)

Alvarez, J.L.; Barrera, R.; Miranda, J.

2002-01-01

In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico

Spatial distribution patterns of energy deposition and cellular radiation effects in lung tissue following simulated exposure to alpha particles

International Nuclear Information System (INIS)

Hofmann, W.; Crawford-Brown, D.J.

1990-01-01

Randomly oriented sections of rat tissue have been digitised to provide the contours of tissue-air interfaces and the locations of individual cell nuclei in the alveolated region of the lung. Sources of alpha particles with varying irradiation geometries and densities are simulated to compute the resulting random pattern of cellular irradiation, i.e. spatial coordinates, frequency, track length, and energy of traversals by the emitted alpha particles. Probabilities per unit track lengths, derived from experimental data on in vitro cellular inactivation and transformation, are then applied to the results of the alpha exposure simulations to yield an estimate of the number of both dead and viable transformed cells and their spatial distributions. If lung cancer risk is linearly related to the number of transformed cells, the carcinogenic risk for hot particles is always smaller than that for a uniform nuclide distribution of the same activity. (author)

The clearance of uranium after deposition of the nitrate and bicarbonate in different regions of the rat lung

International Nuclear Information System (INIS)

Ellender, M.

1987-01-01

This study investigated the tissue distribution and excretion of uranium after its deposition as either the nitrate or bicarbonate in the three regions of the respiratory system of the rat. Results confirm the recommendations of ICRP that uranyl nitrate and bicarbonate should be treated as class D compounds; but imply that some of the parameters used in the ICRP lung model are not applicable to soluble uranium compounds. (author)

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

Directory of Open Access Journals (Sweden)

Suk Peng Tang

2017-01-01

Full Text Available Paraquat (PQ is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day, Tualang honey (1.0 g/kg/day, or ubiquinol (0.2 g/kg/day throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week or PQ (10 mg/kg/week once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p<0.05. The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

Caspase 3 activity in isolated fetal rat lung fibroblasts and rat periodontal ligament fibroblasts: cigarette smoke-induced alterations

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James Elliot Scott

2016-03-01

Full Text Available Background Cigarette smoking is the leading cause of preventable death in the world. It has been implicated in the pathogenesis of pulmonary, oral and systemic diseases. Smoking during pregnancy is clearly a risk factor for the developing fetus and may be a major cause of infant mortality. Moreover, the oral cavity is the first site of exposure to cigarette smoke and may be a possible source for the spread of toxins to other organs of the body. Fibroblasts in general are morphologically heterogeneous connective tissue cells with diverse functions. Apoptosis or programmed cell death is a crucial process during embryogenesis and for the maintenance of homeostasis throughout life. Deregulation of apoptosis has been implicated in abnormal lung development in the fetus and disease progression in adults. Caspases, are proteases which belong to the family of cysteine aspartic acid proteases and are the key components for the downstream amplification of intra-cellular apoptotic signals. Of the 14 caspases known, caspase-3 is the key executioner of apoptosis. Fetal rat lung fibroblasts but not PDL viability is reduced by exposure to CSE. In addition Caspase 3 activity is elevated after CSE exposure in fetal lung fibroblasts but not in PDLs. Expression of caspase 3 is induced in CSE exposed lung fibroblasts but not in PDLs. Caspase 3 was localized to the cytoplasm in both cell types.

Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

Science.gov (United States)

Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

2014-02-01

Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

Role of macrophages and oxygen radicals in IgA induced lung injury in the rat

International Nuclear Information System (INIS)

Johnson, K.J.; Ward, P.A.; Kunkel, R.G.; Wilson, B.S.

1986-01-01

Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to dinitrophenol (DNP) coupled to albumin. This model of lung injury requires an intact complement system but not neutrophils, and evidence suggests that pulmonary macrophages are the critical effector cell. Macrophages retrievable from the lungs of the IgA immune complex treated rats are considerably increased in number as compared to control animals which received only the antibody. In addition these cells show evidence of activation in vivo with greater spontaneous generation of the superoxide anion (O 2 - ) as well as significantly enhanced O 2 - response in the presence of a second stimulus. Inhibition studies in vivo suggest that the lung injury is mediated by oxygen radical generation by the pulmonary macrophages. Pretreatment of rats with superoxide dismutase (SOD), catalase, the iron chelator deferoxamine or the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) all markedly suppressed the development of the lung injury. In summary, these studies suggest that IgA immune complex injury in the rat lung is mediated by oxygen radical formation from pulmonary macrophages

The tissue distribution and excretion study of paeoniflorin-6'-O-benzene sulfonate (CP-25) in rats.

Science.gov (United States)

Zhao, Mingyi; Zhou, Peng; Yu, Jun; James, Asenso; Xiao, Feng; Wang, Chun; Wei, Wei

2018-03-09

Paeoniflorin-6'-O-benzene sulfonate (code: CP-25) is a novel ester derivative of paeoniflorin (Pae). Compared to Pae, CP-25 has higher lipid solubility, bioavailability and better bioactivity. However, the tissue distribution and excretion of CP-25 still remain unknown. The LC-MS method was applied to investigate the tissue distribution and excretion of CP-25 in rats. As such, 50 mg/kg of CP-25 and Pae were administered to rats in multiple doses via an oral route. CP-25 and Pae were distributed widely and rapidly in all the tested tissues. Compared with Pae, the concentrations of CP-25 were almost increased evidently in most tissues. The highest CP-25 level was found in the liver (1476.33 ± 535.20 ng/g, male; 1970.38 ± 177.21 ng/g, female) at 3 h, and a high concentration of CP-25 was detected in male and female intestine, synovium, muscle, lung, and brain. Following a single oral dose of 50 mg/kg of CP-25 in rats, the total excretion of CP-25 was merely 21.8% (18.40, 3.19 and 0.22% for feces, bile and urine, respectively) in males; and was approximately 21.3% (14.04, 7.16 and 0.14% for feces, bile and urine, respectively) in females. The results indicated that the CP-25 concentration was higher in major tissues than Pae; CP-25 was primarily excreted through the feces; and there were gender-related differences in the tissue distribution and excretion.

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

Science.gov (United States)

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

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Jones, D R; Hoffmann, S C; Sellars, M; Egan, T M

1997-05-01

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

Science.gov (United States)

Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

2014-03-01

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

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Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late

Preliminary studies on gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats

International Nuclear Information System (INIS)

Liu Chunjie; Wang Dewen; Zhang Zhaoshan; Gao Yabing; Xiong Chengqi; Long Jianyin; Wang Huixin; Peng Ruiyun; Cui Xuemei

2001-01-01

Objective: To observed the efficiency of gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats. Methods: TGFβ1 sense and antisense gene expression vectors and adenovirus transfer vector were introduced into rat bronchus by way of intratracheal instillation. Results: At day 1.5 after TGFβ1 sense and antisense gene transfer, PCR amplification using neo gene-specific primer from lung tissue DNA was all positive. After day 5.5, 67% (2/3) of lung tissue DNA was positive. RNA dot blot hybridization indicated that TGFβ1 mRNA content of lung tissue transfected with pMAMneo-antiTGFβ1 gene decreased. Detection of lung hydroxyproline (Hyp) content after day 35 of gene transfer showed that even in lung of rats received pMAMneo-AntiTGFβ1 lipid complexes it raised remarkably (P 9 pfu/ml were instilled into bronchus at 0.5 ml per rat. After day 2 day 6, the lung tissues of all six rats (three per each group )expressed the transfected luciferase gene by luminometer. Conclusion: Cationic lipid-mediated TGFβ1 antisense gene therapy was a simple and easy method. It can slow down the course of pathogenesis of lung fibrosis. Replication-deficient recombinant adenovirus-mediated gene therapy of lung diseases is a good and efficient method

Kinetics of tissue distribution and elimination of 4,4'-methylene bis(2-chloroaniline) in rats

International Nuclear Information System (INIS)

Tobes, M.C.; Brown, L.E.; Chin, B.; Marsh, D.D.

1983-01-01

The tissue distribution kinetics and elimination of 4,4'-methylene bis(2-chloroaniline) (MBOCA) in rats was studied after a single dose of [ 14 C]MBOCA (0.49 mg/kg body weight, i.v.). The highest concentrations of radioactivity were in the small intestine, liver, adipose, lung, kidney, skin, and adrenals. For most tissues, a rapid decrease in radioactivity was followed by a slower decrease except for the small intestine, adipose and skin which demonstrated transient increases. Subcellular distribution in liver at 1 h showed radioactivity in all cell fractions. Although very lipophilic, [ 14 C]MBOCA was completely eliminated within 48 h with the major route via the feces (73.4%). (Auth.)

Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

International Nuclear Information System (INIS)

Lubawy, W.C.; Valentovic, M.A.; Atkinson, J.E.; Gairola, G.C.

1983-01-01

Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14 C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14 C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

Combined effects of sivelestat and resveratrol on severe acute pancreatitis-associated lung injury in rats.

Science.gov (United States)

Wang, Houhong; Wang, Shuai; Tang, Amao; Gong, Huihui; Ma, Panpan; Chen, Li

2014-08-01

Despite extensive research and clinical efforts made in the management of acute pancre-atitis during the past few decades, to date no effective cure is available and the mortality from severe acute pancre-atitis remains high. Given that lung is the primary cause of early death in acute pancreatitis patients, novel therapeutic approaches aiming to prevent lung injury have become a subject of intensive investigation. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase, is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat and/or resveratrol in the protection against acute pancreatitis-associated lung injury. The extended analyses demonstrated the following: (1) sodium taurocholate induced apparent lung injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells in the lung, as well as biochemical aberrations in the blood (an increase in amylase concentration and a decrease in partial arterial oxygen pressure) and increases in activities of reactive oxygen species, interleukin 6, myeloperoxidase, neutrophil elastase, lung edema, bronchotracho alveolar lavage protein concentration, and bronchotracho alveolar lavage cell infiltration in the lung; and (2) in lung tissues, either sivelestat or resveratrol treatment effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. In addition, combined treatment with both sivelestat and resveratrol demonstrated additive protective effects on pancreatitis-associated lung injury compared with single treatment.

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

Science.gov (United States)

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

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.

Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

Science.gov (United States)

Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

2014-01-01

Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

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Bakeine, G.J. [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste (Italy)], E-mail: jamesbakeine1@yahoo.com; Di Salvo, M. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bertolotti, A.; Nano, R. [Department of Animal Biology University of Pavia, Piazza Botta, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C. [Department of Surgery University of Pavia, Piazza Botta, Pavia (Italy); Marchetti, A. [Scientific Research Office, Fondazione San Matteo University Policlinic, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy)

2009-07-15

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

International Nuclear Information System (INIS)

Bakeine, G.J.; Di Salvo, M.; Bortolussi, S.; Stella, S.; Bruschi, P.; Bertolotti, A.; Nano, R.; Clerici, A.; Ferrari, C.; Zonta, C.; Marchetti, A.; Altieri, S.

2009-01-01

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure.

Science.gov (United States)

Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ ( p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

Science.gov (United States)

Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418

Response of tissue lysosomes in Gamma-irradiated rats and possible modulation through diclofenac treatment

International Nuclear Information System (INIS)

Hassan, S.H.S.; Abu-Ghadeer, A.R.M.; Osman, S.A.A.

1995-01-01

The effect of pre and post-irradiation treatment of rats with diclofenac (5 mg kg-1) for modulating the damaging effect of radiation on tissue lysosomes was investigated. The parameters used for this study were the activity level of acid phosphatase (ACP) and acid ribonuclease (RNase) activities, both being hydrolytic enzymes of lysosomes. The activities of ACP and RNase in liver, spleen, intestine, kidney, lung and brain were determined at different times up to 14 days after irradiation (4(Gy). Lysosomal affection was represented by time dependent significant increase in ACP activity in all the tissue homogenates of the investigated organs 3, 7 and 14 days after irradiation at 4 Gy. Gamma irradiation at 4 Gy resulted also in a significant rise in RNase activity of all the tissue organs 3 days post-irradiation. However, gradual decrease in the enzyme activity was recorded 7 and 14 days following irradiation. Diclofenac, pre (as prophylactic) and post (as therapeutic) irradiation treatment of rats successfully restored the increase in the enzymatic activities of ACP and RNase nearly to their normal levels in all the investigated organs. The beneficial effect of diclofenac inhibited completely the effect of irradiation at 14 days post-exposure. 2 figs., 2 tabs

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

Science.gov (United States)

Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

2017-01-01

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Science.gov (United States)

Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

2017-06-01

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

Automating the expert consensus paradigm for robust lung tissue classification

Science.gov (United States)

Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

2012-03-01

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

DOPA, norepinephrine, and dopamine in rat tissues

DEFF Research Database (Denmark)

Eldrup, E; Richter, Erik; Christensen, N J

1989-01-01

We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...

C-Psilocin tissue distribution in pregnant rats after intravenous administration

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Francis C.P. Law

2014-06-01

Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

Insulin Treatment Cannot Promote Lipogenesis in Rat Fetal Lung in Gestational Diabetes Mellitus Because of Failure to Redress the Imbalance Among SREBP-1, SCAP, and INSIG-1.

Science.gov (United States)

Li, Jinyan; Qian, Guanhua; Zhong, Xiaocui; Yu, Tinghe

2018-03-01

Gestational diabetes mellitus (GDM) has a higher incidence of neonatal respiratory distress syndrome, and lipogenesis is required for the synthesis of pulmonary surfactants. The aim of this study was to determine the effect of insulin treatment in GDM on the production of lipids in the lungs of fetal rats. GDM was induced by streptozotocin, and insulin was used to manage diabetes. Type II alveolar epithelial cells (AEC II), bronchoalveolar lavage fluid (BALF), and lung tissues of the neonatal rats were sampled for analyses. Insulin treatment could not decrease plasma glucose to normal level at a later gestational stage. Lipids/phospholipids in AEC II, BALF, and lung tissues decreased in GDM, and insulin treatment could not increase the levels; quantitative PCR and western blotting demonstrated a lower level of sterol regulator element-binding protein 1 (SREBP-1), SREBP cleavage-activating protein (SCAP), and insulin-induced gene 1 (INSIG-1) in GDM, but insulin treatment upregulated only SREBP-1. Nuclear translocation of the SREBP-1 protein in AEC II was impaired in GDM, which could not be ameliorated by insulin treatment. These findings indicated that insulin treatment in GDM cannot promote lipogenesis in the fetal lung because of failure to redress the imbalance among SREBP-1, SCAP, and INSIG-1.

Data-driven classification of ventilated lung tissues using electrical impedance tomography

International Nuclear Information System (INIS)

Gómez-Laberge, Camille; Hogan, Matthew J; Elke, Gunnar; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2011-01-01

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F I O 2 ). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F I O 2 decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting

Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

Science.gov (United States)

Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

2011-02-28

3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

Tracking Regional Tissue Volume and Function Change in Lung Using Image Registration

Directory of Open Access Journals (Sweden)

Kunlin Cao

2012-01-01

Full Text Available We have previously demonstrated the 24-hour redistribution and reabsorption of bronchoalveolar lavage (BAL fluid delivered to the lung during a bronchoscopic procedure in normal volunteers. In this work we utilize image-matching procedures to correlate fluid redistribution and reabsorption to changes in regional lung function. Lung CT datasets from six human subjects were used in this study. Each subject was scanned at four time points before and after BAL procedure. Image registration was performed to align images at different time points and different inflation levels. The resulting dense displacement fields were utilized to track tissue volume changes and reveal deformation patterns of local parenchymal tissue quantitatively. The registration accuracy was assessed by measuring landmark matching errors, which were on the order of 1 mm. The results show that quantitative-assessed fluid volume agreed well with bronchoscopist-reported unretrieved BAL volume in the whole lungs (squared linear correlation coefficient was 0.81. The average difference of lung tissue volume at baseline and after 24 hours was around 2%, which indicates that BAL fluid in the lungs was almost absorbed after 24 hours. Regional lung-function changes correlated with the presence of BAL fluid, and regional function returned to baseline as the fluid was reabsorbed.

Quantification of regional early stage gas exchange changes using hyperpolarized {sup 129}Xe MRI in a rat model of radiation-induced lung injury

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Doganay, Ozkan, E-mail: ozkan.doganay@oncology.ox.ac.uk [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Stirrat, Elaine [Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8 (Canada); McKenzie, Charles [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Schulte, Rolf F. [General Electric Global Research, Munich 85748 (Germany); Santyr, Giles E. [Department of Medical Biophysics, Western University, London, Ontario N6A5C1 (Canada); Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A5C1 (Canada); Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G1L7 (Canada)

2016-05-15

Purpose: To assess the feasibility of hyperpolarized (HP) {sup 129}Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a {sup 60}Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (L{sub PT}) and relative blood volume (V{sub RBC}) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in L{sub PT} and V{sub RBC} were observed between the irradiated and non-irradiated cohorts. In particular, L{sub PT} of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, V{sub RBC} of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the

Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats.

Science.gov (United States)

Safdar, Zeenat; Yiming, Maimiti; Grunig, Gabriele; Bhattacharya, Jahar

2005-10-15

Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine.

Science.gov (United States)

Balestrini, Jenna L; Gard, Ashley L; Gerhold, Kristin A; Wilcox, Elise C; Liu, Angela; Schwan, Jonas; Le, Andrew V; Baevova, Pavlina; Dimitrievska, Sashka; Zhao, Liping; Sundaram, Sumati; Sun, Huanxing; Rittié, Laure; Dyal, Rachel; Broekelmann, Tom J; Mecham, Robert P; Schwartz, Martin A; Niklason, Laura E; White, Eric S

2016-09-01

Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal model

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Qihua GU

2008-08-01

Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

Kinetics of tissue distribution and elimination of 4,4'-methylene bis(2-chloroaniline) in rats

Energy Technology Data Exchange (ETDEWEB)

Tobes, M.C.; Brown, L.E.; Chin, B.; Marsh, D.D. (Michigan Univ., Ann Arbor (USA). Medical Center)

1983-06-01

The tissue distribution kinetics and elimination of 4,4'-methylene bis(2-chloroaniline) (MBOCA) in rats was studied after a single dose of (/sup 14/C)MBOCA (0.49 mg/kg body weight, i.v.). The highest concentrations of radioactivity were in the small intestine, liver, adipose, lung, kidney, skin, and adrenals. For most tissues, a rapid decrease in radioactivity was followed by a slower decrease except for the small intestine, adipose and skin which demonstrated transient increases. Subcellular distribution in liver at 1 h showed radioactivity in all cell fractions. Although very lipophilic, (/sup 14/C)MBOCA was completely eliminated within 48 h with the major route via the feces (73.4%).

Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

International Nuclear Information System (INIS)

Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

2009-01-01

Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

Testing an aflatoxin B1 gene signature in rat archival tissues.

Science.gov (United States)

Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

2012-05-21

Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced

Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours

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Bortolussi, S., E-mail: silva.bortolussi@pv.infn.i [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Protti, N.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Clerici, A.; Ferrari, C.; Cansolino, L.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, via Ferrata 27100 Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, via Ferrata 27100 Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

2011-02-15

Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and {alpha}-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

Science.gov (United States)

2014-01-01

Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

Radiation-induced hypoxia may perpetuate late normal tissue injury

International Nuclear Information System (INIS)

Vujaskovic, Zeljko; Anscher, Mitchell S.; Feng, Q.-F.; Rabbani, Zahid N.; Amin, Khalid; Samulski, Thaddeus S.; Dewhirst, Mark W.; Haroon, Zishan A.

2001-01-01

Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

A novel rat genomic simple repeat DNA with RNA-homology shows triplex (H-DNA)-like structure and tissue-specific RNA expression

International Nuclear Information System (INIS)

Dey, Indranil; Rath, Pramod C.

2005-01-01

Mammalian genome contains a wide variety of repetitive DNA sequences of relatively unknown function. We report a novel 227 bp simple repeat DNA (3.3 DNA) with a d {(GA) 7 A (AG) 7 } dinucleotide mirror repeat from the rat (Rattus norvegicus) genome. 3.3 DNA showed 75-85% homology with several eukaryotic mRNAs due to (GA/CU) n dinucleotide repeats by nBlast search and a dispersed distribution in the rat genome by Southern blot hybridization with [ 32 P]3.3 DNA. The d {(GA) 7 A (AG) 7 } mirror repeat formed a triplex (H-DNA)-like structure in vitro. Two large RNAs of 9.1 and 7.5 kb were detected by [ 32 P]3.3 DNA in rat brain by Northern blot hybridization indicating expression of such simple sequence repeats at RNA level in vivo. Further, several cDNAs were isolated from a rat cDNA library by [ 32 P]3.3 DNA probe. Three such cDNAs showed tissue-specific RNA expression in rat. pRT 4.1 cDNA showed strong expression of a 2.39 kb RNA in brain and spleen, pRT 5.5 cDNA showed strong expression of a 2.8 kb RNA in brain and a 3.9 kb RNA in lungs, and pRT 11.4 cDNA showed weak expression of a 2.4 kb RNA in lungs. Thus, genomic simple sequence repeats containing d (GA/CT) n dinucleotides are transcriptionally expressed and regulated in rat tissues. Such d (GA/CT) n dinucleotide repeats may form structural elements (e.g., triplex) which may be sites for functional regulation of genomic coding sequences as well as RNAs. This may be a general function of such transcriptionally active simple sequence repeats widely dispersed in mammalian genome

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

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Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

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Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

2003-10-01

Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

Quantitation and renewal of alveolar and bronchiolar cell populations of rat lungs. Changes during some pathological processes

International Nuclear Information System (INIS)

Fritsch, Paul.

1979-02-01

The various cells of alveolar and bronchiolar tissues of rat lungs were studied qualitatively and quantitatively. In physiological conditions, the renewal rate of the cell populations is low and the frequency of the various cell types is constant. This stability, especially at the level of the alveolar tissue, was also found during the latency period and the development of radiation-induced lung cancers. A particular cellular population was demonstrated: marginated leukocyte pool at the level of the pulmonary circulation. This pool was different both qualitatively and quantitatively from the leukocytes of the systemic circulation and, in physiological conditions, behaved as a cellular reservoir of monocytes chiefly re-distributed according to the body needs. In pathological conditions, its fast migration contributed to the defence of the alveolar medium. A quantitative study of the renewal of alveolar macrophages showed that under 1 p. cent of the marginated leukocyte pool is used daily to keep up this population. This fraction undergoes a maturation stage by cellular division within the endoalveolar medium. In some pathological conditions, this division can be completely inhibited [fr

Quantification of regional early stage gas exchange changes using hyperpolarized "1"2"9Xe MRI in a rat model of radiation-induced lung injury

International Nuclear Information System (INIS)

Doganay, Ozkan; Stirrat, Elaine; McKenzie, Charles; Schulte, Rolf F.; Santyr, Giles E.

2016-01-01

Purpose: To assess the feasibility of hyperpolarized (HP) "1"2"9Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a "6"0Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (L_P_T) and relative blood volume (V_R_B_C) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in L_P_T and V_R_B_C were observed between the irradiated and non-irradiated cohorts. In particular, L_P_T of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, V_R_B_C of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both

5α-reductase activity in rat adipose tissue

International Nuclear Information System (INIS)

Zyirek, M.; Flood, C.; Longcope, C.

1987-01-01

We measured the 5 α-reductase activity in isolated cell preparations of rat adipose tissue using the formation of [ 3 H] dihydrotestosterone from [ 3 H] testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5α-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10 -8 M), when added to the medium, caused a 90% decrease in 5α-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5α-reductase activity in each tissue studied

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

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Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

2017-04-01

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

The uptake and metabolism of cystamine and taurine by isolated, ventilated and perfused rat and rabbit lungs

International Nuclear Information System (INIS)

Sharma, R.; Kodavanti, U.P.; Smith, L.L.; Mehendale, H.M.

1991-01-01

Cystamine has been reported to be taken up by the lung slices and metabolized to taurine via hypotaurine through enzymatic processes. The objective of these studies was to determine whether intact isolated, ventilated and perfused rat and rabbit lungs also posses similar characteristics. The lungs were isolated from male New Zealand white rabbits and S-D rats and perfused with 20 μM [ 14 C] cystamine (Sp. Act., 16.4 mCi/mmol) for 60 min and 30 min, respectively. Cystamine and its metabolites in lung as well as in perfusate were separated by TLC and quantitated using scintillation spectrometry. Similar experiments were also conducted with 20 μM taurine to investigate its fate in perfused lungs. Significant pulmonary uptake of cystamine and taurine occurred during perfusion. Cystamine was metabolized to [ 14 C] hypotaurine and [ 14 C] taurine. No further metabolism of taurine was evident in rat or rabbit lungs. Inclusion of 1 nM GSH did not significantly alter the ability of lungs to sequester cystamine, but the metabolism of hypotaurine to taurine was decreased. It was evident that cystamine was metabolized to taurine by perfused lungs in the same way as in lung slices

Expression of circadian gens in different rat tissues is sensitive marker of in vivo silver nanoparticles action

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Minchenko, D. O.; Yavorovsky, O. P.; Zinchenko, T. O.; Komisarenko, S. V.; Minchenko, O. H.

2012-09-01

Circadian factors PER1, PER2, ARNTL and CLOCK are important molecular components of biological clock system and play a fundamental role in the metabolism at both the behavioral and molecular levels and potentially have great importance for understanding metabolic health and disease, because disturbance the circadian processes lead to developing of different pathology. The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronics, home products, and for water disinfection, but little is yet known about their toxicity. These nanoparticles induce blood-brain barrier destruction, astrocyte swelling, cause degeneration of neurons and impair neurodevelopment as well as embryonic development. We studied the expression of genes encoded the key molecular components of circadian clock system in different rat organs after intratracheally instilled silver nanoparticles which quite rapidly translocate from the lungs into the blood stream and accumulate in different tissues. We have shown that silver nanoparticles significantly affect the expression levels of PER1, PER2, ARNTL and CLOCK mRNA in different rat tissues in time-dependent and tissue-specific manner. High level of PER1, ARNTL and CLOCK mRNA expression was observed in the lung on the 1st 3rd and 14th day after treatment of rats with silver nanoparticles. At the same time, the expression level of PER1 mRNA in the brain and liver increases predominantly on the 1st and 14th day but decreases in the testis. Significant increase of the expression level of PER2 and ARNTL mRNA was detected only in the brain of treated by silver nanoparticles rats. Besides that, intratracheally instilled silver nanoparticles significantly reduced the expression levels of CLOCK mRNA in the brain, heart and kidney. No significant changes in the expression level of PER2 mRNA were found in the lung, liver, heart and testis, except kidney where this mRNA expression decreases on the 3rd and 14th

OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

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REYHANEH SEPEHR

2013-07-01

Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations

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Pan, L.C.; Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. (Department of Veterinary Pharmacology, University of California, Davis (United States))

1991-09-01

Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. The authors previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with (14C)MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, they compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of (14C)MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with (14C)MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM (14C)MCT increased the covalent binding to the lung from 97 {plus minus} 25 (buffer alone) to 182 {plus minus} 36 (buffer + RBC) pmol/mg protein.

Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations

International Nuclear Information System (INIS)

Pan, L.C.; Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J.

1991-01-01

Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. The authors previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with [14C]MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, they compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of [14C]MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with [14C]MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM [14C]MCT increased the covalent binding to the lung from 97 ± 25 (buffer alone) to 182 ± 36 (buffer + RBC) pmol/mg protein

Lung involvement in systemic connective tissue diseases

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Plavec Goran

2008-01-01

Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Supplementation with vitamin A enhances oxidative stress in the lungs of rats submitted to aerobic exercise.

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Gasparotto, Juciano; Petiz, Lyvia Lintzmaier; Girardi, Carolina Saibro; Bortolin, Rafael Calixto; de Vargas, Amanda Rodrigues; Henkin, Bernardo Saldanha; Chaves, Paloma Rodrigues; Roncato, Sabrina; Matté, Cristiane; Zanotto-Filho, Alfeu; Moreira, José Cláudio Fonseca; Gelain, Daniel Pens

2015-12-01

Exercise training induces reactive oxygen species production and low levels of oxidative damage, which are required for induction of antioxidant defenses and tissue adaptation. This process is physiological and essential to improve physical conditioning and performance. During exercise, endogenous antioxidants are recruited to prevent excessive oxidative stress, demanding appropriate intake of antioxidants from diet or supplements; in this context, the search for vitamin supplements that enhance the antioxidant defenses and improve exercise performance has been continuously increasing. On the other hand, excess of antioxidants may hinder the pro-oxidant signals necessary for this process of adaptation. The aim of this study was to investigate the effects of vitamin A supplementation (2000 IU/kg, oral) upon oxidative stress and parameters of pro-inflammatory signaling in lungs of rats submitted to aerobic exercise (swimming protocol). When combined with exercise, vitamin A inhibited biochemical parameters of adaptation/conditioning by attenuating exercise-induced antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreasing the content of the receptor for advanced glycation end-products. Increased oxidative damage to proteins (carbonylation) and lipids (lipoperoxidation) was also observed in these animals. In sedentary animals, vitamin A decreased superoxide dismutase and increased lipoperoxidation. Vitamin A also enhanced the levels of tumor necrosis factor alpha and decreased interleukin-10, effects partially reversed by aerobic training. Taken together, the results presented herein point to negative effects associated with vitamin A supplementation at the specific dose here used upon oxidative stress and pro-inflammatory cytokines in lung tissues of rats submitted to aerobic exercise.

Alteration of phospholipase D activity in the rat tissues by irradiation

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Choi, M. S. [Korea Univ., Seoul (Korea, Republic of). Coll. of Medicine; Cho, Y. J. [Hanyang Univ., Seoul (Korea, Republic of). Coll. of Medicine; Choi, M. U. [Seoul National Univ. (Korea, Republic of). Coll. of Natural Sciences

1997-09-01

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. The reaction mixture for the PLD assay contained 0.1{mu}Ci 1,2-di[1-{sup 14}C]palmitoyl phosphatidylcholine, 0.5mM phosphatidylcholine, 5mM sodium oleate, 0.2% taurodeoxycholate, 50mM HEPES buffer(pH 6.5), 10mM CaCl{sub 2}, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cm x 10cm and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward {gamma}-ray with more than two times amplification in their activities. In contrast, the PLD activity of bone marrow appears to be reduced to nearly 30%. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation strongly indicates that the PLD is closely related to the physiological function of these organs. Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell proliferation to cell death on these organs. (author).

Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

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Deise Riba Coelho

2014-07-01

Full Text Available Meglumine antimoniate (MA and sodium stibogluconate are pentavalent antimony (SbV drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous. Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h and a slow (t1/2 >> 24 h elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain. The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model.

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Romero, A; Moreno, A; García, J; Sánchez, C; Santos, M; García, J

2016-01-01

Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Identification and target prediction of miRNAs specifically expressed in rat neural tissue

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Tu Kang

2009-05-01

Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

Reduced generation of lung tissue-resident memory T cells during infancy.

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Zens, Kyra D; Chen, Jun Kui; Guyer, Rebecca S; Wu, Felix L; Cvetkovski, Filip; Miron, Michelle; Farber, Donna L

2017-10-02

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant-T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. © 2017 Zens et al.

Novel pharmacokinetic studies of the Chinese formula Huang-Lian-Jie-Du-Tang in MCAO rats.

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Zhu, Huaxu; Qian, Zhilei; He, Feng; Liu, Mengzhu; Pan, Linmei; Zhang, Qichun; Tang, Yuping

2013-07-15

Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues. First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT. Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0.25 h), the distribution phase (1.0 h) and the elimination phase (8.0 h) after administration of the HLJDT aqueous extract. An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues. The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney. To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues. The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease. Copyright © 2012 Elsevier GmbH. All rights reserved.

Genomic instability in quartz dust exposed rat lungs: Is inflammation responsible?

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Albrecht, C; Schins, R P F [Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich Heine University Duesseldorf (Germany); Demircigil, G Cakmak; Coskun, Erdem [Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara (Turkey); Schooten, F J van [Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Health Risk Analysis and Toxicology, University of Maastricht (Netherlands); Borm, P J A [Centre of Expertise in Life Sciences (Cel), Hogeschool Zuyd, Heerlen (Netherlands); Knaapen, A M, E-mail: catrin.albrecht@uni-duesseldorf.d

2009-02-01

Exposure to quartz dusts has been associated with lung cancer and fibrosis. Although the responsible mechanisms are not completely understood, progressive inflammation with associated induction of persistent oxidative stress has been discussed as a key event for these diseases. Previously we have evaluated the kinetics of pulmonary inflammation in the rat model following a single intratracheal instillation of 2mg DQ12 quartz, either in its native form or upon its surface modification with polyvinylpyridine-N-oxide or aluminium lactate. This model has been applied now to evaluate the role of inflammation in the kinetics of induction of DNA damage and response at 3, 7, 28, and 90 days after treatment. Bronchoalveolar lavage (BAL) cell counts and differentials as well as BAL fluid myeloperoxidase activity were used as markers of inflammation. Whole lung homogenate was investigated to determine the induction of the oxidative and pre-mutagenic DNA lesion 8-hydroxy-2-deoxy-guanosine (8-OHdG) by HPLC/ECD, while mRNA and protein expression of oxidative stress and DNA damage response genes including hemeoxygenase-1 (HO-1) and apurinic/apyrimidinic endonuclease (APE/Ref-1) were evaluated using Western blotting and real time PCR. Isolated lung epithelial cells from the treated rats were used for DNA strand breakage analysis using the alkaline comet assay as well as for micronucleus scoring in May-Gruenwald-Giemsa stained cytospin preparations. In the rats that were treated with quartz, no increased 8-OHdG levels were observed, despite the presence of a marked and persistent inflammation. However, DNA strand breakage in the lung epithelial cells of the quartz treated rats was significantly enhanced at 3 days, but not at 28 days. Moreover, significantly enhanced micronucleus frequencies were observed for all four time points investigated. In the animals that were treated with the PVNO modified quartz, micronuclei scores did not differ from controls, while in those treated with

Interstitial lung disease associated with connective tissue diseases

International Nuclear Information System (INIS)

Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

2007-01-01

An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

Taurine content of tissues of irradiated rats

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Akhalaya, M.Ya.; Bogatyrev, G.P.; Kudryashov, Yu.B.; Yartsev, E.I.

1976-01-01

The taurine content of tissues (liver, stomach, small intestine and spleen) of rats irradiated with doses of 700 and 450 rads has been studied. Phase changes have been found in the taurine content of radiosensitive tissues in the course of radiation injury development

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

International Nuclear Information System (INIS)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, Josje H.E.; Kuper, C. Frieke; Bloksma, Nanne; Henricks, Paul A.J.

2006-01-01

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

Leukemia inhibitory factor in rat fetal lung development: expression and functional studies.

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Cristina Nogueira-Silva

Full Text Available BACKGROUND: Leukemia inhibitory factor (LIF and interleukin-6 (IL-6 are members of the family of the glycoprotein 130 (gp130-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. METHODOLOGY/PRINCIPAL FINDINGS: LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. CONCLUSIONS/SIGNIFICANCE: The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.

The Effect of Water Contaminated with Methyl Tertiary Butyl Ether (MTBE) on the Rat's Weight and Tissue

International Nuclear Information System (INIS)

Backer, Wadiah Saleh; AboKhatwa, Ahmed Nabil; Katouah, Hanadi Ahmed

2008-01-01

Lead is known to cause deleterious effects on health and environment. Therefore, it was removed from car-fuel, in the United States since 1979. In January 2001, Saudi Arabia and other Arabian Gulf States, replaced lead with a synthetic organic substance called methyl tertiary-butyl ether (MTBE). MTBE is added to gasoline at 12-15%. It dissolves readily in water and evaporates quickly. This study was focused on the possible health hazards of MTBE in drinking water as manifested by changes in weight and vital tissues (heart, liver, kidney, lung, and testis) of rat. This study also aimed to establish a quantitative relationship between MTBE concentration and changes that occur to these tissues. One hundred and twenty male Wistar rats were exposed to five different MTBE concentrations (0.0, 1,000, 1,500, 2,000, 2,500 ppm) for 60 days. The results showed that most of MTBE-treated animals have revealed significant weight loss and the maximum weight loss (nearly 10 %) was achieved at the highest concentration (2,500 ppm) after 60 days of treatment. Also, both liver and heart weights were significantly reduced by almost 9%, and kidneys by 8% of MTBE concentration of 2,000 ppm. At a higher concentration (2,500 ppm), liver weight was reduced by 12%. The weight of other tissues (lungs and testes) remained unchanged. The outcome of the results may lead to hepatic disorder. This disorder could reduce plasma glucose, or increase some hepatic markers like ALT, AST, and GGT activity, or elevate the levels of sodium and chloride in plasma and may have other side effects. (author)

NF-κB inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

International Nuclear Information System (INIS)

Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

2008-01-01

Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-κB) in this process. Exposure of rats to 80 mg/m 3 tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-κB activity, noted by suppression of inhibitor of κB (IκB) kinase (IKK), accumulation of IκBα, decrease of NF-κB DNA binding activity, and downregulation of NF-κB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-κB pathway in tobacco smoke-induced apoptosis

Assessment of the effects of levosimendan and thymoquinone on lung injury after myocardial ischemia reperfusion in rats

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Sezen SC

2018-05-01

Full Text Available Şaban Cem Sezen,1 Aysegul Kucuk,2 Abdullah Özer,3 Yiğit Kılıç,4 Barış Mardin,3 Metin Alkan,5 Fatmanur Duruk Erkent,5 Mustafa Arslan,5 Yusuf Ünal,5 Gürsel Levent Oktar,3 Murat Tosun6 1Department of Histology and Embryology, Kirikkale University Medical Faculty, Kirikkale, Turkey; 2Department of Physiology, Dumlupinar University Medical Faculty, Kutahya, Turkey; 3Department of Cardiovascular Surgery, Gazi University Medical Faculty, Ankara, Turkey; 4Pediatric Cardiovascular Surgery Clinic, Dr Siyami Ersek Cardiovascular and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey; 5Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, Turkey; 6Department of Histology and Embryology, Afyon Kocatepe University Medical Faculty, Afyonkarahisar, Turkey Aim: The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ on lung injury after myocardial ischemia/reperfusion (I/R. Materials and methods: Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group, left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 μg/kg (IRL group, and I/R-thymoquinone (0.2 mL/kg (IRTQ group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies. Results: Increased expression of p53 and Bax was observed (4+, especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+. H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

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Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dosimetry of inhaled plutonium-239 dioxide in rodent lung: a morphometric study

International Nuclear Information System (INIS)

Rhoads, K.

1979-06-01

Morphometric analysis of rat and hamster lung did not demonstrate any extensive changes in lung composition or structure following inhalation exposure to 239 Pu0 2 at levels near that for maximum tumor yield in rats. The problem of dosimetry for this compound thus appears to be relatively uncomplicated by any major radiation-induced pathological alterations in the lung. Rat and hamster lung were found to be similar in structure and composition, with few significant differences which could be directly related to the different tumor responses. The distribution of 239 Pu0 2 particles was not uniform in all regions of the lung; thus estimation of the dose to specific tissues or regions within the lung requires a correction for this effect. Species differences were found for particle distribution in the subpleural region and major airways, and in the spatial association of particles, both of which may affect the tumor development process. These regions contain the principal target cells for tumor production and serve as foci for the origin of tumors. Different dose distributions within these regions may therefore explain, at least in part, the difference in tumor response to inhaled 239 Pu0 2 for rats and hamsters

Tritium metabolism in rat tissues

International Nuclear Information System (INIS)

Takeda, H.

1982-01-01

As part of a series of studies designed to evaluate the relative radiotoxicity of various tritiated compounds, metabolism of tritium in rat tissues was studied after administration of tritiated water, leucine, thymidine, and glucose. The distribution and retention of tritium varied widely, depending on the chemical compound administered. Tritium introduced as tritiated water behaved essentially as body water and became uniformly distributed among the tissues. However, tritium administered as organic compounds resulted in relatively high incorporation into tissue constituents other than water, and its distribution differed among the various tissues. Moreover, the excretion rate of tritium from tissues was slower for tritiated organic compounds than for tritiated water. Administrationof tritiated organic compounds results in higher radiation doses to the tissues than does administration of tritiated water. Among the tritiated compounds examined, for equal radioactivity administered, leucine gave the highest radiation dose, followed in turn by thymidine, glucose, and water. (author)

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

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Jones, D R; Becker, R M; Hoffmann, S C; Lemasters, J J; Egan, T M

1997-07-01

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Endogenous synthesis of taurine and GABA in rat ocular tissues

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Heinaemaeki, A.A.

1988-01-01

The endogenous production of taurine and ..gamma..-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye.

Endogenous synthesis of taurine and GABA in rat ocular tissues

International Nuclear Information System (INIS)

Heinaemaeki, A.A.

1988-01-01

The endogenous production of taurine and γ-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye. (author)

Effects of emissions from sugar cane burning on the trachea and lungs of Wistar rats.

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Matos, Verena Sampaio Barbosa; Gomes, Felipe da Silva; Oliveira, Tarcio Macena; Schulz, Renata da Silva; Ribeiro, Lídia Cristina Villela; Gonzales, Astria Dias Ferrão; Lima, Januário Mourão; Guerreiro, Marcos Lázaro da Silva

2017-01-01

To evaluate the effects of exposure to emissions from sugar cane burning on inflammatory mechanisms in tissues of the trachea and lung parenchyma in Wistar rats after different periods of exposure. This was an experimental open randomized study. The animals were divided into four groups: a control group (CG) underwent standard laboratory conditions, and three experimental groups were exposed to emissions from sugar cane burning over different periods of time, in days-1 (EG1), 7 (EG7), and 21 (EG21). After euthanasia with 200 mg/kg of ketamine/xylazine, fragments of trachea and lung were collected and fixed in 10% formalin. Histological analyses were performed with H&E and picrosirius red staining. No inflammatory infiltrates were found in the tissues of CG rats. The histological examination of tissues of the trachea and lung parenchyma revealed that the inflammatory process was significantly more intense in EG7 than in the CG (p edema, together with polymorphonuclear cell infiltrates. Avaliar os efeitos da exposição à fumaça da queima da cana-de-açúcar sobre mecanismos inflamatórios em tecidos de traqueia e de parênquima pulmonar de ratos Wistar após diferentes períodos de exposição. Estudo experimental, randomizado, não cego. Os animais foram divididos em quatro grupos: controle (GC), sob condições padrão de laboratório e os demais expostos à fumaça da queima da cana-de-açúcar por diferentes períodos: em 1 (GE1), 7 (GE7) e 21 (GE21) dias. Após a eutanásia com 200 mg/kg de ketamina/xilazina, foram coletados fragmentos de traqueia e pulmão e fixadas em formol 10%. Análises histológicas foram realizadas com coloração com H&E e picrosírius. Não houve infiltrado inflamatório nos tecidos no GC. O processo inflamatório na análise histológica de tecidos de traqueia e de parênquima pulmonar foi significativamente mais intenso no GE7 quando comparado ao GC (p pulmonar e aumento significativo de depósitos de colágeno em tecido de

Desferrioxamine Reduces Oxidative Stress in the Lung Contusion

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Umit Nusret Basaran

2013-01-01

Full Text Available Our hypothesis in this study is that desferrioxamine (DFX has therapeutic effects on experimental lung contusions in rats. The rats were divided into four groups (n=8: control, control+DFX, contusion, and contusion+DFX. In the control+DFX and contusion+DFX groups, 100 mg/kg DFX was given intraperitoneally once a day just after the contusion and the day after the contusion. Contusions led to a meaningful rise in the malondialdehyde (MDA level in lung tissue. MDA levels in the contusion+DFX group experienced a significant decline. Glutathione levels were significantly lower in the contusion group than in the control group and significantly higher in the contusion+DFX group. Glutathione peroxidase (GPx and superoxide dismutase (SOD levels in the contusion group were significantly lower than those in the control group. In the contusion+DFX group, SOD and GPx levels were significantly higher than those in the contusion group. In light microscopic evaluation, the contusion and contusion+DFX groups showed edema, hemorrhage, alveolar destruction, and leukocyte infiltration. However, histological scoring of the contusion+DFX group was significantly more positive than that of the contusion group. The iNOS staining in the contusion group was significantly more intensive than that in all other groups. DFX reduced iNOS staining significantly in comparison to the contusion group. This study showed that DFX reduced oxidative stress in lung contusions in rats and histopathologically ensured the recovery of the lung tissue.

Methimazole protects lungs during hepatic ischemia-reperfusion injury in rats: an effect not induced by hypothyroidism.

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Tütüncü, Tanju; Demirci, Cagatay; Gözalan, Ugur; Yüksek, Yunus Nadi; Bilgihan, Ayse; Kama, Nuri Aydin

2007-05-01

Hepatic ischemia-reperfusion injury may lead to remote organ failure with mortal respiratory dysfunction. The aim of the present study was to analyze the possible protective effects of methimazole on lungs after hepatic ischemia-reperfusion injury. Forty male Wistar albino rats were randomized into five groups: a control group, in which bilateral pulmonary lobectomy was done; a hepatic ischemia-reperfusion group, in which bilateral pulmonary lobectomy was done after hepatic ischemia-reperfusion; a thyroidectomy-ischemia-reperfusion group (total thyroidectomy followed by, 7 days later, bilateral pulmonary lobectomy after hepatic ischemia-reperfusion); a methimazole-ischemia-reperfusion group (following methimazole administration for 7 days, bilateral pulmonary lobectomy was done after hepatic ischemia-reperfusion); and a methimazole +L-thyroxine-ischemia-reperfusion group (following methimazole and L-thyroxine administration for 7 days, bilateral pulmonary lobectomy was performed after hepatic ischemia-reperfusion). Pulmonary tissue specimens were evaluated histopathologically and for myeloperoxidase and malondialdehyde levels. All of the ischemia-reperfusion intervention groups had higher pulmonary injury scoring indices than the control group (P < 0.001). Pulmonary injury index of the ischemia-reperfusion group was higher than that of both the methimazole-supplemented hypothyroid and euthyroid groups (P = 0028; P = 0,038, respectively) and was similar to that of the thyroidectomized group. Pulmonary tissue myeloperoxidase and malondialdehyde levels in the ischemia-reperfusion group were similar with that in the thyroidectomized rats but were significantly higher than that in the control, and both the methimazole-supplemented hypothyroid and euthyroid groups. Methimazole exerts a protective role on lungs during hepatic ischemia-reperfusion injury, which can be attributed to its anti-inflammatory and anti-oxidant effects rather than hypothyroidism alone.

Changes of inflammatory cells in rat lungs exposed to diesel emissions; Diesel haiki bakuro ni yoru rat hai no ensho saibo no henka

Energy Technology Data Exchange (ETDEWEB)

Kato, A. [Japan Automobile Research Institute Inc., Tsukuba (Japan); Kagawa, J. [Tokyo Women`s Medical College, Tokyo (Japan)

1998-05-01

Study was made on the effect of exposure to diesel emissions on inflammatory cells in a rat lungs. Four kinds of exposure gases with different contents of NO2 and particulate were prepared by diluting diesel emissions. Rats were exposed to diluted diesel emissions for 24 months, and inflammatory cells were detected morphologically in light microscopic and TEM specimens. As a result, particle-laden- alveolar macrophages increased dose- and time-dependently into the submucosa of intrapulmonary bronchioles, alveolar spaces and interstitume of alveolar walls, and bronchoassociated lymphatic tissues. Mast cells infiltrated into the interspaces of epithelial cells in airways. In the submucosa of the terminal bronchioles and the interstitume of alveolar walls, some sorts of inflammatory cells such as mast cells, plasma cells, neutrophils and lymphocytes infiltrated, and some cells showed cell-to-cell contacts. However, the airways were rarely injured by infiltration of inflammatory cells except for a fibrotic change. 2 refs., 2 figs., 2 tabs.

Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

Science.gov (United States)

Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

2018-03-01

Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

DEFF Research Database (Denmark)

Johansen, H K; Espersen, F; Pedersen, S S

1993-01-01

We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes...

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

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Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

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Said Said Elshama

2016-01-01

Full Text Available Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.

Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog.

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Lande, Rachel; Dvorak, Laura; Gardiner, David W; Bahr, Anne

2015-01-01

A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.

Pulmonary response to ozone: Reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat

International Nuclear Information System (INIS)

Dziedzic, D.; Wright, E.S.; Sargent, N.E.

1990-01-01

The purpose of this work is to assess the effect of ozone, a reactive product of environmental photochemical oxidation, on lymphocytes of the lung. We exposed male Fischer rats to ozone at a concentration of 0.5 ppm for 20 hr/day for 1-14 days. Animals were treated with radioactive thymidine and were sacrificed at Day 1, 2, 3, 7, or 14 of exposure. Lungs and mediastinal lymph nodes were removed and prepared for histologic examination, evaluation of labeling indexes, and morphometric measurement. We examined two components of the lymphocyte response of the lung: the airway-related response, represented by the reaction of the bronchus-associated lymphoid tissue (BALT), and the deep lung-related response, represented by reaction of the mediastinal lymph node. Lymphocytes of both the BALT and the mediastinal lymph node showed elevated radioactive thymidine uptake; however, no evidence of cell death was observed at either site. The cells of the specialized epithelium covering the BALT (lymphoepithelium) showed increased vacuolization, indicating altered cellular function. The average size of BALTs was unchanged by ozone exposure. Under experimental conditions ozone can affect a variety of cells in the lung including bronchial epithelial cells, macrophages, and Type 1 cells. We have shown for the first time that in addition to these cells, the rat BALT also proliferates in response to ozone. In addition we confirm previous work in the mouse which shows that the mediastinal lymph node reacts as well. The airways can be affected by inflammation, can be targets of infection, and can respond to chemical irritants with bronchoconstrictive responses. They are an important target organ for hypersensitivity responses and are a primary site for pulmonary cancer formation. A role for lymphocytes has been implicated in each of these processes

Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations.

Science.gov (United States)

Franchi, A M; Di Girolamo, G; de los Santos, A R; Martí, M L; Gimeno, M A

1998-06-01

Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic activity that produces minor digestive side-effects. This fact induced us to think that LC is possibly a weak COX-1 inhibitor. In order to investigate our hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and control rats. Rat lung preparations incubated with 14C-arachidonic acid synthesise mainly PGE2. LC at 2.5 and 4.1 x 10(-5) M does not modify the basal production of PGE2 (probably COX-1) but at 6.8 x 10(-5) M significantly inhibited PGE2 production (approximately 48.5% inhibition, P<0.001). On the other hand, INDO at 10(-6) inhibited the basal production of PGE2 by around 73%. In LPS-treated rats, the production of PGE2 was significantly higher than in the lungs of control rats, probably due to the induction of COX-2. The addition of LC at 2.7 and 4.1 x 10(-5) M recovered the control values of PGE2 inhibiting, probably only from COX-2 activity. LC at higher concentrations (6.8 x 10(-5) M) and INDO 10(-6) M inhibited PGE2 formed by COX-2 and also partly by COX-1 activity.

Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

International Nuclear Information System (INIS)

Dano, Laurent

2000-01-01

Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

Distribution characteristics of liquid sequestration in rats with sepsis

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Bin LI

2012-03-01

Full Text Available Objective　To investigate the distribution characteristics of organs with liquid sequestration during fluid resuscitation in rats with sepsis. Methods　Fifty male Wistar rats were randomly divided into five groups: control group (n=10, sepsis group (n=10, crystalloid group (n=10, albumin group (n=10, and artificial colloid (HAES group (n=10. The sepsis model was reproduced by cecal ligation and puncture. The mean arterial pressure was monitored with carotid artery intubation. Twelve hours after fluid infusion by micro-infusion pump via the femoral vein, tissues from the heart, liver, lungs, kidney (right, and small intestine were harvested to observe the pathological changes and calculate the tissue water content. Results　The water content of every visceral tissue was higher in the sepsis group than in the control group (P < 0.05; the water content in the heart, liver, and lung tissues was higher in the albumin group than in the crystalloid group (P < 0.05. The water content in both albumin and crystalloid groups was higher than that in the sepsis group (P < 0.05. Moreover, the water content in the heart, liver, and lungs in the HAES group was lower than that in the crystalloid and albumin groups (P < 0.05. Cellular injuries were more severe in the heart, liver, and lungs than in the intestine and kidney in the crystalloid group and albumin group under electron-microscope. Conclusion Liquid sequestration exists mainly in the lungs, heart, and liver of rats with sepsis during fluid resuscitation. The phenomenon is less evident in the kidney and small intestine. Artificial colloid can reduce capillary leak with a good volume expansion effect.

Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

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Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

2012-01-01

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague–Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase–glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase–glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague–Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

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Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2?mL/kg/day), Tualang honey (1.0?g/kg/day), or ubiquinol (0.2?g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were i...

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

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Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

International Nuclear Information System (INIS)

Kodama, Tetsuro

1978-01-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

Energy Technology Data Exchange (ETDEWEB)

Kodama, T [Hiroshima Univ. (Japan). School of Medicine

1978-08-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining.

Effect of lung resection and sham surgery on the frequency of infection in alloxan-diabetic rats

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A.C. Seidel

2003-03-01

Full Text Available The present study was carried out in order to determine the effect of lung resection on the frequency of infections in alloxan-diabetic rats. Adult female Wistar rats were injected with alloxan (40 mg/kg, iv to induce diabetes mellitus (group D; N = 45 or with vehicle (1.0 ml/kg, iv to be used as controls (group C; N = 45. Thirty-six days after receiving alloxan both groups were randomly divided into three subgroups: no operation (NO; N = 15, sham operation (SO; N = 15, and left pneumonectomy (PE; N = 15. The rats were sacrificed 36 days after surgery and their lungs were examined microscopically and macroscopically. The occurrence of thoracic wall infection, thoracic wall abscess, lung abscess and pleural empyema was similar in groups D and C. In contrast, the overall infection rate was higher (P<0.05 in the diabetic rats (SO-D and PE-D subgroups, but not in the NO-D subgroup. Considering that the overall infection rate was similar in the SO-D and PE-D subgroups, we suggest that surgery but not pneumonectomy was related to the higher prevalence of infection in diabetic rats.

Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

Science.gov (United States)

1984-10-01

lung tumor system the specific aims are: 1. To conduct studies of the effect of 3-methylchlanthrene (MCA) on DNA synthesis and cell proliferation in...alkylation of nucleic acids of the rat by N-methyl-N- nitrosourea , dimethylnitrosamine, dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

Time course of lung inflammatory and fibrogenic responses during protective mechanical ventilation in healthy rats.

Science.gov (United States)

Krebs, Joerg; Pelosi, Paolo; Tsagogiorgas, Charalambos; Haas, Jenny; Yard, Benito; Rocco, Patricia R M; Luecke, Thomas

2011-09-15

This study aimed to assess pulmonary inflammatory and fibrogenic responses and their impact on lung mechanics and histology in healthy rats submitted to protective mechanical ventilation for different experimental periods. Eighteen Wistar rats were randomized to undergo open lung-mechanical ventilation (OL-MV) for 1, 6 or 12 h. Following a recruitment maneuver, a decremental PEEP trial was performed and PEEP set according to the minimal respiratory system static elastance. Respiratory system, lung, and chest-wall elastance and gas-exchange were maintained throughout the 12 h experimental period. Histological lung injury score remained low at 1 and 6 h, but was higher at 12 h due to overinflation. A moderate inflammatory response was observed with a distinct peak at 6h. Compared to unventilated controls, type I procollagen mRNA expression was decreased at 1 and 12h, while type III procollagen expression decreased throughout the 12h experimental period. In conclusion, OL-MV in healthy rats yielded overinflation after 6 h even though respiratory elastance and gas-exchange were preserved for up to 12 h. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Effect of two tumors (metastatic and non-metastatic) on tissue distribution of Ga-67 citrate in the rat

International Nuclear Information System (INIS)

Durakovic, A.

1985-01-01

The effect of metastatic and non-metastatic mammary adenocarcinoma on tissue distribution of Ga-67 citrate in Fischer female rats was studied. The homogenate (0.1 ml) of each tumor was injected subcutaneously in separate groups of rats and the animals were studied from day 2-30 after tumor homogenate implantation. All animals were injected with 30 μCi of Ga-67 citrate and sacrificed by halothane anethesia 48 hours later. Tissue samples of blood, lung, heart, liver, spleen, kidney, adrenal, stomach, small and large intestine, ovaries, and lymph nodes (popliteal, lumbar, and mediastinal) were obtained and counted in a gamma well counter. The control group consisted of four animals and tumor bearing groups of seven to eight animals at each time. Ga-67 uptake was increased in the liver (24 days) and in the popliteal lymph nodes on days 7, 10, and 18 in the metastatic tumor group (P<0.05). This probably represents Ga-67 uptake in the metastatic deposits in these organs. No difference was observed in non-metastatic tumor group

Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

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Lominiki Slawo

2011-03-01

Full Text Available Abstract Background Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM. The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs, in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. Methods Neonatal rats (7-days of age were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP, non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. Results Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. Conclusions Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes.

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

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Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

2015-10-05

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1.

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Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

2014-12-01

Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression.

Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

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Carpenter, Laurie Jean

When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

Effect of bitter gourd and spent turmeric on constituents of glycosaminoglycans in different tissues in streptozotocin induced diabetic rats.

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Kumar, G Suresh; Vijayalakshmi, B; Salimath, P V

2006-06-01

Diet is now one of the well established means in the management of diabetes. Bitter gourd and spent turmeric at 10% level were tested for their efficacy on glycosaminoglycan metabolism in various tissues viz., liver, spleen, lungs, heart and testis in control, diabetic and treated rats. The glycosaminoglycans (GAGs) were isolated from defatted and dried tissues. The contents of sulfated GAGs decreased in all the tissues and the decrease was more prominent in heart and testis. In the isolated GAGs, contents of total sugar, amino sugar, uronic acid and sulfate were studied. Decrease in total sugar content was maximum in testis. Amino sugar content decreased considerably in testis (38%) and lungs (15%). The content of uronic acid also decreased in testis (33%) besides heart (29%) and liver (25%). Sulfate groups in GAGs perform pivotal functions in many biological events and decrease in sulfate content was significant in heart (40%), testis (37%) and liver (37%). GAGs profile on the cellulose acetate electrophoresis revealed that heparan sulfate (HS), hyaluronic acid (HA) and chondroitin sulfate/dermatan sulfate (CS/DS) were present in liver, spleen and lungs. HS, CS were present in heart, DS/CS was observed in testis. The observed beneficial effects in GAGs metabolism during diabetes may be due to the presence of high amounts of dietary fibres present in bitter gourd and spent turmeric, besides, possible presence of bioactive compounds in one or both of them.

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

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Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

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Viktor M Pastukh

2011-03-01

Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

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Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

1993-04-01

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats.

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Liu, Zibing; Geng, Wenye; Jiang, Chuanwei; Zhao, Shujun; Liu, Yong; Zhang, Ying; Qin, Shucun; Li, Chenxu; Zhang, Xinfang; Si, Yanhong

2017-09-01

Chronic obstructive pulmonary disease induced by tobacco smoke has been regarded as a great health problem worldwide. The purpose of this study is to evaluate the protective effect of hydrogen-rich saline, a novel antioxidant, on chronic obstructive pulmonary disease and explore the underlying mechanism. Sprague-Dawley rats were made chronic obstructive pulmonary disease models via tobacco smoke exposure for 12 weeks and the rats were treated with 10 ml/kg hydrogen-rich saline intraperitoneally during the last 4 weeks. Lung function testing indicated hydrogen-rich saline decreased lung airway resistance and increased lung compliance and the ratio of forced expiratory volume in 0.1 s/forced vital capacity in chronic obstructive pulmonary disease rats. Histological analysis revealed that hydrogen-rich saline alleviated morphological impairments of lung in tobacco smoke-induced chronic obstructive pulmonary disease rats. ELISA assay showed hydrogen-rich saline lowered the levels of pro-inflammatory cytokines (IL-8 and IL-6) and anti-inflammatory cytokine IL-10 in bronchoalveolar lavage fluid and serum of chronic obstructive pulmonary disease rats. The content of malondialdehyde in lung tissue and serum was also determined and the data indicated hydrogen-rich saline suppressed oxidative stress reaction. The protein expressions of mucin MUC5C and aquaporin 5 involved in mucus hypersecretion were analyzed by Western blot and ELISA and the data revealed that hydrogen-rich saline down-regulated MUC5AC level in bronchoalveolar lavage fluid and lung tissue and up-regulated aquaporin 5 level in lung tissue of chronic obstructive pulmonary disease rats. In conclusion, these results suggest that administration of hydrogen-rich saline exhibits significant protective effect on chronic obstructive pulmonary disease through alleviating inflammation, reducing oxidative stress and lessening mucus hypersecretion in tobacco smoke-induced chronic obstructive pulmonary disease rats

A morphological study of bronchi and lung tissues in long-term survived dogs

OpenAIRE

松本, 伸

1984-01-01

Morphological changes of the bronchus and lung tissue of ten adult dogs were examined at various intervals after sleeve resection of the left upper lobe was performed in combination with bronchoplasty and pulmonary artery angioplasty. Postoperative changes in the bronchus and pulmonary artery were investigated by bronchoscopy and pulmonary angiography 8 months to 14 months after the operation. The dogs were sacrificed 9 months to 32 months after the operation, and the bronchus and lung tissue...

Tissue disposition of bifenthrin in the rat

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U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

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Haiyan ZHENG

2010-08-01

Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspa- se-3-mediated Apoptosis Induction

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Sikdar Sourav

2013-09-01

Full Text Available Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP in white rats (Rattus norvegicus. Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one (5th, two (5th-6th and three (5th-7th months, respectively, and were sacrificed at the corresponding time- points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM, annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR, immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two- month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR expression, a

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

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Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Experimental study of sucralfate intervention for paraquat poisoning in rats.

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Junbo, Zhu; Yongtao, Yu; Hongbo, Li; Fenshuang, Zheng; Ruyun, Lin; Chun'ai, Yang

2017-07-01

This study explored the effects of sucralfate intervention as a novel treatment for paraquat (PQ) poisoning in Sprague-Dawley (SD) rats. After PQ poisoning, the SD rats were randomly divided into the PQ control group (treated with normal saline), the sodium bicarbonate (SB) treatment group, and the sucralfate (LTL) treatment group. Then, the rats were administered normal saline, sodium bicarbonate solution, or sucralfate suspension as an intervention by gastric lavage. At 1, 3, 6, and 10days after poisoning, the left lungs of some rats were removed to determine the lung wet/dry (W/D) weight ratio. Additionally, the serum cytokine levels were measured, and the lung and kidney tissues were pathologically examined. After treatment, the signs and symptoms of the rats were improved, the mortality rate was reduced, the W/D weight ratio of the lung was lower, the cytokine levels [transforming growth factor (TGF)-β1, interleukin (IL)-10, and tumor necrosis factor (TNF)-α] were decreased, and the pathological injuries of the lungs and kidneys were improved. Moreover, sucralfate was significantly more effective than the control (normal saline) group and the SB treatment group. The results showed that early gastrointestinal lavage with sucralfate effectively reduced the inflammatory response and lung and kidney injuries and improved the survival of the SD rats. Copyright © 2017 Elsevier B.V. All rights reserved.

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)

Histological changes in lung tissues related with sub-chronic exposure to ambient urban levels of PM2.5 in Córdoba, Argentina

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Tavera Busso, Iván; Vera, Anahí; Mateos, Ana Carolina; Amarillo, Ana Carolina; Carreras, Hebe

2017-10-01

Concentration of fine particulate matter (PM2.5) is one of the most important environmental parameters to estimate health impacts attributable to air pollution. Despite the fact there are many studies regarding PM2.5 effects on human health, most of them were performed under conditions that do not simulate the natural particles interaction with the organism. In the present paper, we studied the effects of mammals' sub-chronic exposure to PM2.5 on the lower respiratory tract, addressing realistic exposure conditions to normal urban air. Thus, we exposed Wistar rats under controlled settings to the same normal urban air, with and without particles. Next, we analyzed chemical composition of PM2.5 and lungs samples, performed a histologic examination and run the comet assay to assess genotoxic effects. We found a strong agreement between lung tissues and PM2.5 elemental composition suggesting that metals found in lungs came from the particles inhaled. Histological analysis showed a mild to moderate infiltration, with a reduction of alveoli lumen and increment of alveolar macrophages and periodic acid-Schiff (PAS) (+) cells in treated animals. We also observed an increase in the number of nuclei with comets, mostly comets type 3, with a high DNA fragmentation as well. These results provide strong evidence that sub-chronic exposure to low particle levels, even below the 24 h WHO standard, can cause injuries in lungs tissues and DNA damage, as well.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

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Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro

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Zhengchang Liao

2016-01-01

Full Text Available Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat

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Wei-Lun Hung

2018-04-01

Full Text Available Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. Keywords: Tangeretin, Oral bioavailability, Pharmacokinetics, Tissue distribution, Excretion

Analysis of ethyl acrylate (EA) and acrylic acid (AA) residues from rat tissues following oral ea dosing

International Nuclear Information System (INIS)

Udinsky, J.R.; Frederick, C.B.

1990-01-01

Gavage dosing of rats with EA at high dose levels (100 or 200 mg/kg) has resulted in tumors at the dosing site, forestomach (FST), but no lesions of the glandular stomach (GST) or other remote tissues. Since previous in vitro studies have demonstrated that EA is very rapidly metabolized to AA and glutathione conjugates, EA and AA residues were analyzed 0-24 hr following gavage dosing of non-fasted F-344/N male rats with [1- 14 C]EA in corn oil at 10, 50, and 200 mg/kg. Analysis of total 14 C indicated that the dose solution was primarily in the FST at ≥5 min after dosing, although 14 C was detected in the GST, duodenum, and small intestine (attributed to distension of the FST and leakage from the FST to the GST). HPLC analysis of the gut contents, gut wall, liver, kidneys, lungs, and blood indicated that EA and AA could only be detected at ≥15 min in the FST and GST contents, and in the FST tissue. AA alone was detected in the GST tissue, duodenum tissue and contents, and small intestine tissue and contents. The minimum level of detection was 0.0005% of the dose. The remaining 14 C was primarily attributed to binding to the gut contents or bioincorporation of AA. The detection of EA and AA residues only in the upper gastrointestinal tract following gavage dosing is consistent with rapid detoxification of EA by hydrolysis and conjugation which prevents toxicity at sites remote form the site of dosing

Lung structure-respiratory function relationships in experimentally-induced bronchiolitis, bronchopneumonia and interstitial pneumonia in rats

Energy Technology Data Exchange (ETDEWEB)

Mauderly, J L; Madron, E de; Harkema, J R

1988-12-01

Histopathology and respiratory function of rats with three different types and distributions of lower lung inflammation were compared to better understand lung structure-function relationships. Rats were exposed 21 h/day for 7 days to 0.8 ppm ozone (O{sub 3}), sham-exposed as controls, or given 5 mg/kg bacterial endotoxin either intratracheally (ITE) or intraperitoneally (IPE). Respiratory function was measured 24 h after the end of treatment, than the rats were sacrificed and the distribution of inflammation was evaluated morphometrically. Chronic centriacinar inflammation with formation of new respiratory bronchioles caused an obstructive functional impairment in the O{sub 3} rats, which was clearly distinguished from the restrictive impairments resulting from acute inflammation in ITE and IPE rats. Only the magnitudes of changes related to the distribution of inflammation differentiated the ITE and IPE groups. Flow parameters previously thought sensitive to large airway resistance were changed in the O{sub 3} rats. Alveolar luminal inflammatory exudate affected quasistatic compliance more than septal inflammation in ITE and IPE rats. Quasistatic chord compliance was the most sensitive of three indices of pressure-volume relationships. The findings in this study improve the basis for interpreting respiratory function changes of rats. (author)

Cadmium distribution and selected tissue histology in rats following administration of cadmium chloride and/or gamma radiation

International Nuclear Information System (INIS)

Kundomal, Y.R.

1981-01-01

Sprague-Dawley rats were injected IP with CdCl 2 or distilled water, and/or given a total-body irradiation. Three lethality studies, acute Cd, chronic Cd, and acute radiation, were performed to determine the sublethal doses for the co-insult study. Lethal doses (LD 50 ) were obtained by probit analysis. Cd concentrations were determined by the atomic absorption spectrophotometry. The analysis of variance was used to test the data. LD/sub 50(30)/ values obtained for respective male and female rats were: 5.99 and 7.13 mg/kg of body wt for acute Cd; 4.25 and 5.99 mg/kg of body wt for chronic Cd; and 733 and 729 R for acute radiation. On days 1, 7 and 21 post-irradiation, rats given Cd singly or in combination with radiation showed a high accumulation and retention of metal in the liver and kidney. Then followed in order of decreasing Cd concentrations were: spleen, intestine, stomach, heart, testis, lung, blood cells, brain, and muscle. High Cd concentrations in the liver and kidney persisted over a 21-day observation period; the concentrations in the other tissues decreased, some to control values. Radiation was not an antagonist on Cd concentrations or retentions in these tissues except the heart, in which radiation contributed to the clearance of Cd. Radiation did not act as a synergistic agent on Cd concentrations or retentions in any of the tissues analyzed. Radiation singly had no morphological or physiological effects on the parameters of this study. Based on the high Cd concentrations in these tissues, histological examinations of the liver and kidney sections were made. In the high co-insult groups slight abnormalities, such as pyknotic nuclei in the liver and cellular disorganization and larger lumens in the kidney were observed

A fresh frozen plasma to red blood cell transfusion ratio of 1:1 mitigates lung injury in a rat model of damage control resuscitation for hemorrhagic shock.

Science.gov (United States)

Zhao, Jingxiang; Pan, Guocheng; Wang, Bo; Zhang, Yuhua; You, Guoxing; Wang, Ying; Gao, Dawei; Zhou, Hong; Zhao, Lian

2015-06-01

We aimed to evaluate the effects of resuscitation with different ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary inflammatory injury and to illuminate the beneficial effects of FFP on lung protection compared with lactated ringers (LR) using a rat model of hemorrhagic shock. Rats underwent pressure-controlled hemorrhage for 60 minutes and were then transfused with LR for initial resuscitation. Thereafter, the rats were transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC (1:1) to hold their mean arterial pressure (MAP) at 100 ± 3 mm Hg for 30 minutes. After 4 hours of observation, lung tissue was harvested to determine the wet/dry weight, myeloperoxidase levels, tumor necrosis factor α levels, macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase activity, and the nuclear factor κB p65 DNA-binding activity. With an increase in the FFP:RBC ratio, the volume of required RBC to maintain the target MAP decreased. The MAP value in each group was not significantly different during the whole experiment period. The values of the wet/dry weights and MIP-2 were significantly lower in the FFP:RBC = 1:1 group than the other groups (P ratio of FFP to RBC results in decreased lung inflammation. Compared with LR, FFP could further mitigate lung inflammatory injury. Copyright © 2015. Published by Elsevier Inc.

Tissue levels of iron, copper, zinc and magnesium in iron deficient rats

African Journals Online (AJOL)

The effects of iron deficiency on the levels of iron, copper, zinc and magnesium in the brain, liver, kidney, heart and lungs of albino rats (Rattus novergicus) was investigated. Forty rats were divided into two groups and the first group was fed a control diet containing 1.09g iron/kg diet while the test group was fed diet ...

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.

Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

Science.gov (United States)

Zeitz, Johanna O; Most, Erika; Eder, Klaus

2016-05-31

Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

Science.gov (United States)

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry.

Science.gov (United States)

Christensen, Gary E; Song, Joo Hyun; Lu, Wei; El Naqa, Issam; Low, Daniel A