Preventive Effects of Sivelestat Sodium Hydrate on Lipopolysaccharide-induced Intestinal Paralysis in Conscious Guinea Pigs

Abstract

Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used to treat acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). Effects of the agent on the intestine have not been elucidated. In the present study, the effects of sivelestat were investigated in LPS-induced intestinal paralysis in conscious guinea pigs, about which we reported previously. Intestinal movement and body temperature of guinea pigs were measured successively. Intestinal movement was observed by telemetry using a force transducer installed on the taenia caecum. Simultaneously, body temperature was measured using a plate-type thermometer attached to the dorsum of the animal. On the 4th post-operative day, when intestinal movement was stabilized, lipopolysaccharide (LPS, E. coli, 0111: B4) was administered intraperitoneally. In guinea pigs that received sivelestat 10min before and 1h after LPS administration, the intestinal relaxation and lowering of body temperature 2h after LPS administration were suppressed by sivelestat dose-dependently. Guinea pig plasma elastase activity increased significantly 2h after LPS administration. The increase was suppressed significantly by sivelestat. On histopathological examination, there was no neutrophil accumulation in the taenia caecum 2h after LPS administration at the dose used in the study. The above findings suggest that the neutrophil elastase inhibitor sivelestat is effective for LPS-induced intestinal paralysis.