Cigarette smoke-induced oxidative stress: A role in chronic obstructive pulmonary disease skeletal muscle dysfunction.
BACKGROUND
Inflammation and oxidative stress contribute to muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). Oxidants contained in cigarette smoke (CS) induce adverse effects on tissues through oxidative phenomena.


OBJECTIVE
To explore oxidative stress and inflammation in quadriceps of human smokers and in diaphragm and limb muscles of guinea pigs chronically exposed to CS.


METHODS
Muscle function, protein oxidation and nitration, antioxidants, oxidized proteins, inflammation, creatine kinase activity, and lung and muscle structures were investigated in vastus lateralis of smokers, patients with COPD, and healthy control subjects and in diaphragm and gastrocnemius of CS-exposed guinea pigs at 3, 4, and 6 months.


RESULTS
Compared with control subjects, quadriceps muscle force was mildly but significantly reduced in smokers; protein oxidation levels were increased in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed animals; glycolytic enzymes, creatine kinase, carbonic anydrase-3, and contractile proteins were significantly more carbonylated in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed guinea pigs. Chronic CS exposure induced no significant rise in muscle inflammation in either smokers or rodents. Muscle creatine kinase activity was reduced only in patients with COPD and in both diaphragm and gastrocnemius of CS-exposed animals. Guinea pigs developed bronchiolar abnormalities at 4 months of exposure and thereafter.


CONCLUSIONS
CS exerts direct oxidative modifications on muscle proteins, without inducing any significant rise in muscle inflammation. The oxidative damage to muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle loss and dysfunction in smokers and patients with COPD.
Barreiro
Esther
E
Pulmonology Department, Municipal Institute of Medical Research, Hospital del Mar, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain. ebarreiro@imim.es
Peinado
Víctor I
VI
Galdiz
Juan B
JB
Ferrer
Elisabet
E
Marin-Corral
Judith
J
Sánchez
Francisco
F
Gea
Joaquim
J
Barberà
Joan Albert
JA
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D024403:Carbonic Anhydrase III / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D015151:Immunoblotting; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D003402:Creatine Kinase; D024403:Carbonic Anhydrase III