title: Bovine lactoferrin decreases cholera-toxin-induced intestinal fluid accumulation in mice by ganglioside interaction.
abstract: Secretory diarrhea caused by cholera toxin (CT) is initiated by binding of CT's B subunit (CTB) to GM1-ganglioside on the surface of intestinal cells. Lactoferrin, a breast milk glycoprotein, has shown protective effect against several enteropathogens. The aims of this study were to determine the effect of bovine-lactoferrin (bLF) on CT-induced intestinal fluid accumulation in mice, and the interaction between bLF and CT/CTB with the GM1-ganglioside receptor. Fluid accumulation induced by CT was evaluated in the mouse ileal loop model using 56 BALB/c mice, with and without bLF added before, after or at the same time of CT administration. The effect of bLF in the interaction of CT and CTB with GM1-ganglioside was evaluated by a GM1-enzyme-linked immunosorbent assay. bLF decreased CT-induced fluid accumulation in the ileal loop of mice. The greatest effect was when bLF was added before CT (median, 0.066 vs. 0.166 g/cm, with and without bLF respectively, p<0.01). We conclude that bLF decreases binding of CT and CTB to GM1-ganglioside, suggesting that bLF suppresses CT-induced fluid accumulation by blocking the binding of CTB to GM1-ganglioside. bLF may be effective as adjunctive therapy for treatment of cholera diarrhea.
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. Fulton.Rivera@upch.pe
authors.forename: Fulton P
authors.initials: FP
authors.lastname: Rivera
authors.forename: Anicia M
authors.initials: AM
authors.lastname: Medina
authors.forename: Sandra
authors.initials: S
authors.lastname: Bezada
authors.forename: Roberto
authors.initials: R
authors.lastname: Valencia
authors.forename: María
authors.initials: M
authors.lastname: Bernal
authors.forename: Rina
authors.initials: R
authors.lastname: Meza
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Maves
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Ochoa
mesh_terms: D000818:Animals; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology; D002772:Cholera Toxin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D007781:Lactoferrin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D002712:Chlorides; D004768:Enterotoxins; D005290:Ferric Compounds; D005732:Gangliosides; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D007781:Lactoferrin; C024555:ferric chloride