A novel selectin blocker alleviates oxidative stress of lung reperfusion injury

Takashi Yoshimura, Masahiro Kawashima, Takayuki Nakamura, Noritaka Isowa, Toru Bando, Seiki Hasegawa, Hirosato Kondo, Shinya Toyokuni, Hiromi Wada

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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. Materials and methods. Rat lungs were reperfused at 37°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°C for 90 min. In the OJ-R (+) group, rats received 100 μg 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.

Original languageEnglish
Pages (from-to)91-98
Number of pages8
JournalJournal of Surgical Research
Volume101
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery

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    Yoshimura, T., Kawashima, M., Nakamura, T., Isowa, N., Bando, T., Hasegawa, S., Kondo, H., Toyokuni, S., & Wada, H. (2001). A novel selectin blocker alleviates oxidative stress of lung reperfusion injury. Journal of Surgical Research, 101(1), 91-98. https://doi.org/10.1006/jsre.2001.6258