We have previously shown that oral treatment of an experimental model of shigellosis with sodium butyrate or phenylbutyrate improves clinical outcome and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we have found that Entinostat, an aroylated phenylenediamine compound has similar therapeutic potential against shigellosis. Here, we aim to evaluate Entinostat as a potential candidate for host-directed therapy against cholera in an experimental model. Vibrio cholerae-infected rabbits were treated with two different dose regimen of Entinostat i.e. 0.5 mg twice daily for 2 days and 1 mg once daily for 2 days. Treatment effect on clinical outcomes and shedding of V. cholerae (CFU count in stool) was observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosa. Serum zonulin level was measured by ELISA to evaluate gut permeability. Infection of rabbits with V. cholerae down-regulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with Entinostat at both dose regimens. Level of serum zonulin, a marker of gut permeability was up-regulated after infection, which was counteracted after treatment with Entinostat. Entinostat treatment also led to recovery from cholera and decline in V. cholerae count in stool. In conclusion, improved clinical outcome of treatment with Entinostat in cholera is associated with induction of CAP-18 and reduction of gut epithelial permeability.
http://ift.tt/2oZxQc9
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου