Effects of kynurenine-3-monooxygenase inhibitor GSK180 on sepsis-induced acute lung injury in a mouse model
Gao Rong
Yang Run-hua
Qi Wei
Kan Min-qiang
Gu Wei
Abstract：Objective To investigate the effects of kynurenine-3-monooxygenase (KMO) inhibitor GSK180 on sepsis-induced acute lung injury (ALI) and the underlying mechanism.Methods Sepsis was induced by cecal ligation and puncture (CLP).In the first set of experiment, fifty-six adult male mice were randomly assigned to the following four groups: sham + vehicle group (n=10), sham + GSK180 group (n=10), CLP + vehicle group (n=18), and CLP + GSK180 group (n=18).At 0 or 5 h after CLP or sham operation, mice received an intraperitoneal injection of GSK180 (30 mg/kg of body weight) or the same volume of normal saline.Pulmonary histological scores, wet-to-dry weight ratio (W/D), myeloperoxidase activities (MPO), TUNEL positive cells, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-10, malondialdehyde (MDA) and superoxide dismutase activities (SOD) were assessed at 24 h after operation.The 7 day survival rate was also observed for another set of experiment.Results CLP significantly increased pulmonary histological scores, W/D, MPO, TUNEL positive cells, IL-6, and MDA levels.However, GSK180 treatment significantly decreased these parameters when compared with the CLP + vehicle group (P<0.05).There was no significant difference in survival rate, TNF-α, IL-10, and SOD among the four groups (P>0.05).Conclusion KMO inhibitor GSK180 improves sepsis-induced ALI, probably by down-regulating the inflammation and oxidative stress.
Keywords：SepsisAcute lung injury(ALI)InflammationOxidative stressKynurenine-3-monooxygenase(KMO)
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 406-409 )