Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia

• DOI: 10.1128/aac.02570-16
• Publication Date: 2017-04-25T00:55:26Z
• Authors: Protim Sarker; Atanu Banik; Roger Stromberg; Gudmundur H. Gudm...; Rubhana Raqib; Birgitta Agerberth
• Keywords: Occludin; Cholera; Intestinal Permeability

ABSTRACT We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression antimicrobial peptide CAP-18 large intestinal epithelia. In a subsequent study, we found entinostat, aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. this aimed to evaluate entinostat as candidate for host-directed therapy cholera model. Vibrio cholerae -infected rabbits were treated two different dose regimens entinostat: either 0.5 mg twice daily 2 days 1 once days. The effects on V. shedding (CFU count stool) observed. Immunohistochemical analysis was carried out assess ileal jejunal mucosae. serum zonulin level measured by enzyme-linked immunosorbent assay (ELISA) gut permeability. Infection downregulated epithelium; replenished at regimen. zonulin, marker permeability, upregulated after infection, upregulation counteracted entinostat. Entinostat also led recovery from decline stool. conclusion, improved outcome is associated induction reduction epithelial