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.
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