A novel selectin blocker alleviates oxidative stress of lung reperfusion injury.
BACKGROUND
The importance of reactive oxygen species released through interaction of leukocyte/endothelial cell in ischemia-reperfusion injury of the lung is not yet fully understood. A novel selectin blocker, OJ-R9188, which inhibits the interaction, may alleviate oxidative stress and pulmonary dysfunction after warm ischemia-reperfusion.


METHODS
Rat lungs were reperfused at 37 degrees C for 60 min with an ex vivo model and were divided into three groups (n = 10). In the fresh group, lungs were reperfused immediately after harvest. In the OJ-R (-) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37 degrees C for 90 min. In the OJ-R (+) group, rats received 100 microg per body of OJ-R9188 intravenously 10 min before the harvest. The electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188.


RESULTS
Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in the OJ-R (+) group were significantly lower than those in the OJ-R (-) group. Oxidative DNA damage in the alveolar wall of the OJ-R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2'-deoxyguanosine, was significantly lower than that of the OJ-R (-) group. Immunostaining of 3-nitro-l-tyrosine, which represents nitric oxide-mediated oxidative damage, was also more intense in the OJ-R (-) group than in the OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not observed, and the number of leukocytes infiltrated to the lung tissue as seen by myeloperoxidase activity was not different between the OJ-R (-) and OJ-R (+) groups.


CONCLUSIONS
A novel selectin blocker, OJ-R9188, improves pulmonary function after warm ischemia-reperfusion and alleviates reperfusion-induced oxidative alveolar damage.
Yoshimura
T
T
Department of Thoracic Surgery, Kyoto University, Kyoto, Japan.
Kawashima
M
M
Nakamura
T
T
Isowa
N
N
Bando
T
T
Hasegawa
S
S
Kondo
H
H
Toyokuni
S
S
Wada
H
H
D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D011652:Pulmonary Circulation; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D019087:Selectins / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D016166:Free Radical Scavengers; C441961:O-J-R9188; D017382:Reactive Oxygen Species; D019087:Selectins; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D003849:Deoxyguanosine