Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of theophylline.
To evaluate the potential inhibitory effect of theophylline on the pulmonary oxidative stress in asthma and chronic obstructive pulmonary disease (COPD), we concomitantly measured the blood levels of theophylline, a non-selective phosphodiesterase (PDE) inhibitor and lipid peroxides as an index of oxidative stress. The plasma levels of lipid peroxides were significantly elevated in patients with asthma (3.48 +/- 0.11 nmol ml(-1); mean +/- SEM; n=21, P<0.01), non- or ex-smoking patients with COPD (3.55 +/- 0.11 nmol ml(-1); n = 20, P<0.01), and current-smoking patients with COPD (3.53 +/- 0.15 nmol ml(-1); n = 15, P<0.01), respectively, as compared to those of non-smoking controls (3.02 +/- 0.08 nmol ml(-1); n = 19). There was a significant negative correlation between the plasma level of lipid peroxides and the forced expiratory volume in 1 sec (FEV1)% of forced vital capacity in these subjects (r = -0.304; n = 75, P < 0.01). In asthmatics, there was a significant negative correlation between the plasma level of lipid peroxides and the serum level of theophylline (r = -0.495; n = 18, P<0.05). These results suggest that there may be increased oxidative stress in patients with asthma and COPD, and indicate that oxidative stress could possibly attribute to the pathophysiology of asthma and COPD in leading to airflow obstruction and that theophylline could potentially inhibit oxidative stress in the process of bronchopulmonary inflammation in asthmatics.
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. hideot@showa.gunma-u.ac.jp
H
H
Tsukagoshi
Y
Y
Shimizu
S
S
Iwamae
T
T
Hisada
T
T
Ishizuka
K
K
Iizuka
K
K
Dobashi
M
M
Mori
D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000097:blood; D013806:Theophylline / Q000097:blood / Q000627:therapeutic use*; D014797:Vital Capacity / Q000187:drug effects
D008054:Lipid Peroxides; D010726:Phosphodiesterase Inhibitors; D013806:Theophylline