Carbon monoxide inhalation decreased lung injury via anti-inflammatory and anti-apoptotic effects in brain death rats.
Brain death (BD) induces acute lung injury and makes donor lungs unfit for transplantation. Carbon monoxide (CO) inhalation at 50-500 ppm exerts anti-inflammatory and anti-apoptosis effects in several lung injury models. We examined whether CO inhalation would show favorable effects on lung injury in BD rats. BD rats inhaled 250 ppm CO for two hours. Inhalation decreased the severity of lung injury, as checked by histological examination. CO treatment reversed aggravation in PaO(2)/FiO(2), base excess and pH of BD rats. CO inhalation downregulated the pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6), and inhibited activity of myeloperoxidase in lung tissue. Inhalation significantly decreased cell apoptosis of lungs, and inhibited mRNA expression of intercellular adhesion molecule-1 and caspase-3 in the lungs. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of extracellular signal-regulated kinase expression in the lungs. In conclusion, CO exerts potent protective effects on lungs from BD rats, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase signal transduction.
Zhou
Huacheng
H
Department of Anesthesiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Liu
Jinfeng
J
Pan
Peng
P
Jin
Di
D
Ding
Wengang
W
Li
Wenzhi
W
D055371:Acute Lung Injury / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001926:Brain Death / Q000473:pathology* / Q000503:physiopathology; D002248:Carbon Monoxide / Q000008:administration & dosage*; D053148:Caspase 3 / Q000235:genetics; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016040:Lung Transplantation; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020858:Tissue and Organ Harvesting
D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D002248:Carbon Monoxide; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3