Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma.
OBJECTIVE
Glucocorticoids (GC) may exert therapeutic effects in asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are exposed to oxidative stress, which is believed to be critical in the pathogenesis of asthma. The aim of this study was to investigate whether GC exert a rapid non-genomic effect on oxidative stress in asthmatic guinea pigs.


METHODS
The guinea pig asthma model was used to assess inhibitory effects of budesonide (BUD) on oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and lung manganese superoxide dismutase (MnSOD) activity were measured by spectrophotometry. Superoxide anion production was measured by cytochrome c reduction assay.


RESULTS
Oxidative stress occurred within minutes following antigen challenge and BUD reduced the severity of oxidative stress in asthmatic guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent antioxidant capacity and lung MnSOD activity, as compared with those of vehicle-treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in vitro superoxide anion production by BALF cells and bronchi harvested from sensitized animals. These rapid effects were not blocked by the GC receptor antagonist RU486 and/or the protein synthesis inhibitor cycloheximide.


CONCLUSIONS
BUD reduced oxidative stress in a guinea pig model of asthma by a rapid non-genomic mechanism. These data suggest new mechanisms whereby GC treatments may benefit asthma.
Long
Fei
F
Department of Respiratory Medicine, First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Wang
Yan
Y
Qi
Hui-Hui
HH
Zhou
Xin
X
Jin
Xian-Qiao
XQ
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D018893:Bronchoalveolar Lavage; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D002839:Chromans / Q000378:metabolism; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D002839:Chromans; D005938:Glucocorticoids; D013481:Superoxides; D019819:Budesonide; D013482:Superoxide Dismutase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid