title: Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A.
abstract: Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.
authors.affiliation: Clinical Research Unit & Institute of Biomedicine, School of Medicine, Federal University of Ceará, Brazil.
authors.forename: Andressa A F L
authors.initials: AA
authors.lastname: Maciel
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Braga-Neto
authors.forename: Andréa B
authors.initials: AB
authors.lastname: Braga
authors.forename: Eunice B
authors.initials: EB
authors.lastname: Carvalho
authors.forename: Herene B M
authors.initials: HB
authors.lastname: Lucena
authors.forename: Gerly A C
authors.initials: GA
authors.lastname: Brito
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D018938:Caco-2 Cells; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D017097:Electric Impedance; D004768:Enterotoxins / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D051381:Rats; D014801:Vitamin A / Q000494:pharmacology*