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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury.

The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.[1]

References

  1. Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury. Ishizaka, A., Hasegawa, N., Sakamaki, F., Tasaka, S., Nakamura, H., Kishikawa, K., Yamada, A., Obata, T., Sayama, K., Urano, T. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
 
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