Prophylactic efficacy of enteral miconazole administration for neonatal intestinal perforation and its potential mechanism.

PURPOSE: Intestinal perforation (IP) is a fatal complication in extremely low birth weight infants (ELBWI). We started administrating enteral miconazole (MCZ) to ELBWI in 2002. Since then, the incidence of IP has significantly decreased. The aim of this study was to elucidate the prophylactic effect of MCZ for the treatment of neonatal IP, and to establish a new prophylactic concept for this disease.

METHODS

In in vivo experiments, the effects of MCZ were examined histopathologically using a mouse model of intestinal ischemia. In in vitro experiments, the cytoprotective effect of MCZ against hypoxia was evaluated using Caco-2 intestinal cells, and its anti-inflammatory potential using a co-culture model of Caco-2 and HL60 cells.

RESULTS

MCZ showed a tissue protective effect against intestinal ischemia. MCZ reduced high mobility group-box 1 (HMGB1) release in Caco-2 cells under hypoxic stress and attenuated the potential to activate co-cultured HL60 leukocytes with Caco-2 cells by suppressing interleukin-8 (IL-8).

CONCLUSION

MCZ may have preventive roles in the clinical management of IP in ELBWI by the suppression of IL-8 and HMGB-1.