Lipid peroxidation and 5-lipoxygenase activity in chronic obstructive pulmonary disease.
We studied the urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha) as an index of in vivo oxidant stress, and the production of leukotriene (LT) B(4) (LTB(4)) by neutrophils in subjects with chronic obstructive pulmonary disease (COPD) and normal subjects. Overnight urinary excretion of the isoprostane was significantly higher in patients with COPD than in control subjects, and LTB(4) production by challenge of neutrophils obtained from patients with COPD was also significantly higher than that observed in control neutrophils. Treatment with a standardized polyphenol extract caused a significant decrease in isoprostane excretion, accompanied by a statistically significant increase of Pa(O(2)). Furthermore, changes in FEV(1) significantly correlated with the changes in isoprostane urinary excretion observed from enrollment to the end of treatment. The results of this study suggest that enhanced oxidative stress in subjects with COPD is paralleled by the increased ability of neutrophils to synthesize the chemotactic factor LTB(4), and may ultimately contribute to the infiltration/activation of neutrophils into the airways of subjects with COPD. Antioxidant treatment in subjects with COPD is effective in reducing oxidant stress as shown by the decrease of urinary isoprostane, a reduction that correlates with the severity of the disease, as indicated by changes in Pa(O(2)) and FEV(1).
Santus
Pierachille
P
Department of Pharmacological Sciences, Center for Cardiopulmonary Pharmacology, Via Balzaretti 9, Milan 20133, Italy.
Sola
Alessandra
A
Carlucci
Paolo
P
Fumagalli
Francesca
F
Di Gennaro
Antonio
A
Mondoni
Michele
M
Carnini
Chiara
C
Centanni
Stefano
S
Sala
Angelo
A
D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D007975:Leukotriene B4 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000097:blood; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D012016:Reference Values; D027843:Vitis
D028421:Isoprostanes; D010936:Plant Extracts; C438786:isoprostane F2alpha III; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D010100:Oxygen