Effective therapies against sepsis, which is commonly encountered in critical care units, have been long awaited. In this study, we examined the effects of pre-administered neuraminidase inhibitors, oseltamivir phosphate and zanamivir hydrate, on intestinal paralysis in a lipopolysaccharide (LPS)-induced endotoxicosis model in guinea pigs. 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. Oseltamivir and zanamivir were administrated orally and subcutaneously respectively, one hour prior to administration of LPS. In addition, to examine a neuraminidase activity in guinea pig, the level of free sialic acid in serum was measured using a periodate-resorcinol method. It was revealed that neuraminidase inhibitors, dosedependently prevented intestinal muscle relaxation and decreases in body temperature. Free sialic acid levels in guinea pig serum were decreased, indicating that oseltamivir effectively prevented neuraminidase activity. These results suggest that neuraminidase inhibitors can prevent LPS-induced intestinal paralysis and hypothermia inhibiting neuraminidase activity in guinea pigs, thus have a therapeutic potential for prevention of the worsening of endotoxicosis.
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