Stressantwort in Ozon-induzierten Lungeschäden und deren Modulation durch Ambroxol

Ozon verursacht als wichtiger Luftschadstoff pathologische Veränderungen des Respirationssystems sowie Einschränkungen der Lungenfunktion. Seine Toxizität beruht dabei auf seiner hohen Oxidationskraft mit Auslösung eines „oxidativen Stresses“. Dieser besteht auch unabhängig von Ozon bei Entzündungsr...

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Bibliographic Details
Main Author: Sachse, Mariam Ilse
Contributors: Seifart, Carola (Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
Online Access:PDF Full Text
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Ozone is an important air pollutant that compromises lung function and causes acute lung injury. Cellular injury induces stress related expression of several high conserved proteins. Of those proteins one important group consisits of the heat shock proteins (HSP). Ambroxol, often used in respiratory diseases, is postulated to provide antioxidant properties. To investigate the stress response in ozone-induced lung injury and the potential protection by ambroxol, we analyzed HSP´s protein and mRNA expression in rat whole lung tissue after ozone exposure, with and without ambroxol treatment. Two groups of Sprague Dawley rats (5 each) were exposed to 3ppm ozone for 8 hours. One group was treated with ambroxol, while the other was not. Two groups (6 each) of control animals were not exposed to ozone, either treated with ambroxol or not. Heat shock protein (HSP 32, -60, -70, -73kD) and mRNA expression were analyzed using specific immunoblot and competive PCR. GAPDH were used to normalize mRNA. HSP 32 protein (436%) and mRNA (536%) were significantly increased in ozone exposed animals (% of controls), while exposed animals treated with ambroxol showed dignificant reduction in protein amount (119%). HSP 60 (40,2%), -70 (10,6%) and -73 (9,3%) protein were significant decreased after ozone exposure. This decrease was inhibited by ambroxol in part (HSP 60; 75,8%, HSP 73: 61,3%, HSP 72: 46,5%). HSP 72 mRNA was elevated in ozone exposed animals (248%) with further increase in those teated with ambroxol, while HSP 60 and 73 mRNA were not significantly changed. Ozone induced lung injury results in HSP 32 expression and decreases HSP 60/72/73, while both is inhibited by ambroxol, suggesting that ambroxol may work as an potent antioxidant.