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Allergen-induced formation of F2-isoprostanes in a murine asthma model identifies oxidative stress in acute airway inflammation in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
2009 (English)In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 80, no 1, 1-7 p.Article in journal (Refereed) Published
Abstract [en]

F2-isoprostanes have been associated with various forms of oxidant stress. The levels of F2-isoprostanes in a murine asthma model were studied both in situ and in vivo and further investigated whether the formation of F2-isoprostanes was associated with increased ovalbumin (OVA)-induced airway inflammation after a 17-day (OVA-17) or a 24-day (OVA-24) protocol. Bronchial reactivity was assessed by using a ventilator (FlexiVent). OVA-treated animals had higher lung resistance and lung compliance compared to control groups (P<0.001). 8-Iso-PGF2α levels in bronchoalveolar lavage (BAL) and 8-iso-PGF2α immunoreactivity in lung tissue were analyzed. OVA-17 mice showed a 2.5-fold increased level of 8-iso-PGF2α in BAL compared to PBS-17 mice (P=0.023). Lung tissue from OVA-24 mice had more intense 8-iso-PGF2α staining compared to OVA-17 mice. This study showed an accumulation of F2-isoprostanes in acute airway inflammation and a markedly increased tissue damage caused by oxidative stress in an ongoing inflammation.

Place, publisher, year, edition, pages
2009. Vol. 80, no 1, 1-7 p.
Keyword [en]
Isoprostanes, Animal model, Asthma, Oxidative stress, Lung mechanics, Airway inflammation, In situ
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-99318DOI: 10.1016/j.plefa.2008.10.001ISI: 000264434500001PubMedID: 19081714OAI: oai:DiVA.org:uu-99318DiVA: diva2:212334
Available from: 2009-04-21 Created: 2009-03-11 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Lung mechanics and airway inflammation in murine models of asthma
Open this publication in new window or tab >>Lung mechanics and airway inflammation in murine models of asthma
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Lungmekanik och luftvägsinflammation i djurmodeller för astma
Abstract [en]

Allergic asthma is an inflammatory disease of the airways and is characterized by eosinophilic inflammation and increased airway reactivity. In the studies presented in this thesis, lung mechanics and measurements of airway reactivity were assessed in anaesthetized tracheostomized mice by using an animal ventilator (flexiVent®). A forced oscillation technique makes it possible to measure of both airway and tissue mechanics with a potential to distinguish between central and peripheral airways. The results of the experiments on lung mechanics imply that it is important to understand how altered lung mechanics can affect the airway physiology in order to assess the relevance of different animal models of asthma. We have investigated the effects of changing different components of the lung mechanical measurements, such as administering bronchoconstrictive agents via inhalation or intravenously and implementing deep inhalation in animals with airway inflammation. We have also investigated the relation between airway inflammation and oxidative stress. We found that the formation and time-course of F2-isoprostanes, a marker of oxidative stress, and tissue damage were associated with the degree of inflammation and with the degree of heterogeneous airway airflow. Finally we wished to investigate the hypothesis that nitric oxide (NO) may interact with glucocorticoid (GC) treatment because we see a potential for finding new strategies to increase the therapeutic effect in poor responders or patients resistant to GC treatment. NO plays a central role in physiological regulation of the airway function, and is involved in asthma. We found that the concomitant administration of NO and GC attenuated the airway reactivity more than either treatment alone. In conclusion, with the information presented in this thesis, we hope to contribute to the development of better experimental tools and to improved understanding of murine models of asthma for investigating and understanding the underlying pathophysiology of asthma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 468
Keyword
allergic asthma, airway inflammation, murine models, lung mechanics, forced oscillation technique, airway reactivity, deep inhalations, oxidative stress, nitric oxide, glucocorticoids.
National Category
Physiology
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-107061 (URN)978-91-554-7569-7 (ISBN)
Public defence
2009-09-11, Enghoffsalen, Akademiska Sjukhuset, Ingång 50, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2009-08-21 Created: 2009-07-15 Last updated: 2009-08-21Bibliographically approved

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