Carbon monoxide inhalation protects lung from lipopolysaccharide-induced injury in rat.
Carbon monoxide (CO), a metabolite of heme catalysis by heme oxygenase (HO), has been proposed to have anti-oxidative, anti-inflammatory and anti-apoptotic functions. Lipopolysaccharide (LPS)-induced lung injury (LI) is characterized by oxidative stress, inflammatory reaction and excessive pulmonary cell apoptosis. So we supposed that CO might have protection against LI. LI in rats was induced by intravenous injection of LPS (5 mg/kg). To observe the effect of CO inhalation, LI rats were exposed to 2.5 x 10(-4) (V/V) CO for 3 h. CO-induced changes of lung oxidative stress parameters, inflammatory cytokines, cell apoptosis, HO-1 expression and histology were examined. Results revealed that expressions of the tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6), activities of maleic dialdehyde (MDA) and myeloperoxidase (MPO), and cell apoptosis in LPS injection + CO inhalation group were (0.91+/-0.25) pg/mg protein, (0.64+/-0.05) pg/mg protein, (1.02+/-0.23) nmol/mg protein, (7.18+/-1.62) U/mg protein and (1.60+/-0.34)%, respectively, significantly lower than the corresponding values in LI group [(1.48+/-0.23) pg/mg protein, (1.16+/-0.26) pg/mg protein, (1.27+/-0.33) nmol/mg protein, (8.16+/-1.49) U/mg protein and (3.18+/-0.51) %, P<0.05]. Moreover, CO inhalation obviously increased the expressions of HO-1 and interlukin-10 (IL-10) and activity of superoxide dismutase (SOD) [(5.43+/-0.92), (0.26+/-0.07) pg/mg protein and (60.09+/-10.21) U/mg protein in LPS injection + CO inhalation group vs (3.08+/-0.82), (0.15+/-0.03) pg/mg protein and (50.98+/-6.88) U/mg protein in LI group, P<0.05]. LI was attenuated by CO inhalation. Our study demonstrates that inhalation of low concentration of CO protects lung against LPS-induced injury via anti-oxidant, anti-inflammation, anti-apoptosis and up-regulation of HO-1 expression.
Liu
Shao-Hua
SH
Intensive Care Unit, The First Affiliated Hospital of Nanjing Medicial University, Nanjing 210029, China. Liush67@hotmail.com
Ma
Ke
K
Xu
Bing
B
Xu
Xin-Rong
XR
D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002263:Carboxyhemoglobin / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D051547:Heme Oxygenase-1