Flunisolide attenuates nitric oxide-induced DNA damage in rat trachea epithelial cells.
In asthma the bronchial epithelium is highly abnormal, with various structural changes. As a consequence, the epithelium becomes an important source of inflammatory mediators that contribute to the ongoing inflammation and remodeling responses occurring in asthma. Compared with normal individuals, the fraction of exhaled nitric oxide (NO) is elevated in patients with asthma, and these levels have been shown to vary with disease activity. Thus, in asthma, epithelial cells may be exposed to large amounts of NO. Increased NO production is associated with the formation of various nitrosating species capable of promoting DNA damage. In this study we investigated the effect of NO on DNA of rat trachea epithelial cells in the presence or absence of flunisolide. Rat airway epithelial cells were prepared and incubated with the NO donor S-nitroso-L-glutathione monoethyl ester (GSNO-MEE). DNA damage was evaluated using single cell gel electrophoresis 'comet assay.' The parameters used as an index of DNA damage were tail length, tail intensity, and tail moment. Results of our study demonstrated that NO induced significant DNA damage in rat airway epithelial cells. Flunisolide in amounts of 11-110 mumol/L significantly reduced all the considered parameters indicating DNA damage. These data indicate that flunisolide may protect epithelial cells from the NO-mediated DNA damage. NO overproduction could contribute to epithelial injury in asthma, and flunisolide seems to attenuate this damage.
Kantar
Ahmad
A
Division of Pediatric Medicine, Policlinico San Pietro, Ponte San Pietro, Bergamo, Italy.
Porcelli
Filippo
F
Fiocchi
Alessandro
A
Fedeli
Donatella
D
Marconi
Antonella
A
Falcioni
Giancarlo
G
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D014132:Trachea / Q000187:drug effects
D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester