Nitric oxide-mediated activation of NADPH oxidase by salbutamol during acute asthma in children.
A wide variety of reactive oxygen species (ROS) such as superoxide anion, hydroxyl radical and hydrogen peroxide, and reactive nitrogen species such as nitric oxide (NO) and peroxynitrite are known to be involved in pathophysiology of bronchial asthma. We have investigated, in this study, the status of NADPH oxidase (NOX), a major source of superoxide anion production, in peripheral blood lymphocytes (PBL) from asthmatic patients in relation to salbutamol treatment. PBL isolated from patients with bronchial asthma were found to have a significantly increased activity of NOX. Plasma levels of malondialdehyde (MDA), an index of lipid peroxidation, and NO were also markedly elevated in asthmatic patients compared to control samples. A significantly decreased catalase activity observed in PBL from our patients underscored the severity of oxidative stress during asthma. Treatment of PBL with salbutamol (10 microg ml(-1)), prevented the attenuation of catalase activity but significantly increased the levels of NO and NOX activity. Levels of NOX-1 mRNA were significantly (p < 0.001) increased in PBL following treatment with NO donor (500 microM), S-nitroso-N-acetyl penicillamine (SNAP). Western blot analysis revealed that gp91phox protein was also significantly (twofold-threefold) increased following treatment with SNAP. The observed transcriptional regulation of NOX-1 and gp91phox by NO was observed to result in an increased NOX activity as well. This study concludes that salbutamol treatment enhances superoxide anion production in asthma patients through NO-mediated mechanisms, however it exerts beneficial antioxidant effects through activation of catalase and attenuation of lipid peroxidation.
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait.
Abdullah
A
Owayed
Gursev S
GS
Dhaunsi
Fahad
F
Al-Mukhaizeem
D000208:Acute Disease; D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002675:Child, Preschool; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*
D001993:Bronchodilator Agents; D009569:Nitric Oxide; D019255:NADPH Oxidases; D000420:Albuterol